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Chan-Lin Chu,1,2 Yueh-Peng Chen,3 Carl CP Chen,3,4 Chih-Kuang Chen,3,4 Hsiang-Ning Chang,4 Chien-Hung Chang,1,2,5,* Yu-Cheng Pei3,4,6,7,* 1Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Electrical Engineering, College of Engineering, Chang Gung University, Taoyuan, Taiwan; 6Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan; 7Center of Vascularized Tissue Allograft, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan*These authors contributed equally to this workCorrespondence: Yu-Cheng Pei; Chien-Hung Chang Email yspeii@gmail.com; cva9514@gmail.comBackground: Tailored rehabilitation programs for stroke patients cannot be made without knowledge of their recovery potential. The aim of this study is to characterize the functional recovery patterns of ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients under post-acute care stroke rehabilitation.Methods: This retrospective study analyzed the data of patients enrolled in the Post-Acute Care-Cerebrovascular Disease (PAC-CVD) rehabilitation program, which provides an individualized 1- to 3-hour intensive physical, occupational, and speech and language therapy for post-acute stroke patients in Taoyuan Chang Gung Memorial hospital in Taiwan. Our primary endpoint measure was Barthel Index (BI), and secondary endpoint measures included other 12 functional measures.Results: A total of 489 patients were included for analysis. Patients with stroke history had less BI improvement than those who suffered their first-ever stroke. In first-ever stroke patients who had completed 6 to 12 weeks of PAC-CVD program, subcortical ICH patients had greater BI, quality of life, sensation, and balance improvements, and had greater late-phase recovery than their IS counterparts. In IS patients, those with age > 75 had less BI improvement; those with National Institute of Health Stroke Scale (NIHSS) score 1– 5 had greater Motor Activity Log quality of use (MAL-quality) improvement than those with NIHSS score > 5; those with Mini-Mental State Examination (MMSE) score ≥ 24 had greater BI and instrumental activities of daily living (IADL) improvement. Using the general linear model, previous stroke (ß: − 6.148, p=0.01) and subcortical ICH (ß: 5.04, p=0.03) were factors associated with BI improvement.Conclusion: Subcortical ICH patients have greater functional improvement and greater late-phase recovery than their IS counterparts following PAC rehabilitation. More studies are needed to validate our findings and unravel the underlying mechanisms of stroke recovery to optimize the treatment strategy following a stroke.Keywords: activities of daily living, functional recovery, hemorrhagic stroke, ischemic stroke, post-acute care, rehabilitation

Yu-Ling Chen,1,2 Yu-Cheng Pei3–6 1Department of Music, Southwestern Oklahoma State University, Weatherford, OK, USA; 2Division of Music Education and Music Therapy, University of Kansas, Lawrence, KS, USA; 3Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 4Center of Vascularized Tissue Allograft, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5School of Medicine, Chang Gung University, Taoyuan, Taiwan; 6Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan Background/aims: Dual-task training may improve dual-task gait performance, balance, and cognition in older adults with and without cognitive impairment. Although music has been widely utilized in dementia management, there are no existing protocols for music-based dual-task training. This randomized controlled study developed a Musical Dual-Task Training (MDTT) protocol that patients with dementia can use to practice walking and making music simultaneously, to enhance attention control in patients during dual-tasking.Methods: Twenty-eight adults diagnosed with mild-to-moderate dementia were assigned to the MDTT (n=15) or control groups (n=13). The MDTT group received MDTT, while the control group participated in non-musical cognitive and walking activities. The effects of MDTT were evaluated through the primary outcome of attention control, and secondary outcomes of dual-task performance, balance, falls efficacy, and agitation.Results: The MDTT group showed a significant improvement in attention control, while the control group did not (P

Chih-Chi Chen,1 Chia-Ying Chung,1 Tsong-Hai Lee,2 Wei-Han Chang,1 Simon FT Tang,1 Yu-Cheng Pei1,3 1Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 2Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, 3Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan Background: Cervical spondylosis is one of the extrinsic factors causing vertebral artery stenosis. Several case studies have reported compression of the vertebral artery induced by cervical osteophytes that has resulted in posterior circulation infarcts (POCI). However, to the best of our knowledge, no studies have yet analyzed differences in the risk factors and stroke subtypes between ischemic stroke patients with cervical spondylosis and those without. Purpose: In the case-controlled study reported here, we analyzed the risk factors and stroke subtypes in ischemic stroke patients with and without cervical spondylosis. Characteristics in all the recruited patients with POCI and non-POCI were further compared to extract other risk factors that could predict the occurrence of POCI. Methods and patients: We filtered out ischemic stroke patients with cervical spondylosis (“Stroke+C” group) by International Classification of Diseases, Ninth Revision codes. We analyzed the data of 38 subjects in the Stroke+C group and 152 sex- and age-comparable ischemic stroke patients without cervical spondylosis (“Stroke-C” group). We recorded the demographic characteristics including sex and age, and stroke risk factors, including diabetes mellitus, hypertension, heart disease, hyperlipidemia, and smoking habits. The stroke classifications were defined by the Oxford Community Stroke Project classification. All subjects were further categorized into POCI or non-POCI groups. The ultrasound findings of the vertebral arteries (extracranial and intracranial) in the Stroke+C group were also recorded. Results: More patients in the Stroke+C group tended to have POCI (34.2%) than patients in the Stroke-C group (17.5%) (odds ratio [OR] =2.41, P

Muscle strength is a key component of an athlete's performance and may be influenced by taping. This study examined the possible immediate and delayed effects of Kinesio taping on muscle strength in quadriceps and hamstring when taping is applied to the anterior thigh of healthy young athletes. Fourteen healthy young athletes (seven males and seven females) free of knee problems were enrolled in this study. Muscle strength of the subject was assessed by the isokinetic dynamometer under three conditions: (1) without taping; (2) immediately after taping; (3) 12h after taping with the tape remaining in situ. The result revealed no significant difference in muscle power among the three conditions. Kinesio taping on the anterior thigh neither decreased nor increased muscle strength in healthy non-injured young athletes. [ABSTRACT FROM AUTHOR]

Anxiety experienced when interacting in a foreign language hinders communication through detrimental behavioral, cognitive, and somatic effects. Despite its impact, there is limited research on how neural asymmetry relates to foreign language anxiety (FLA). While researchers have investigated FLA through brain imaging, there remains an absence of studies examining its correlation with frontal alpha asymmetry. Understanding FLA in the context of frontal alpha asymmetry is significant because it can reveal specific neural mechanisms underlying this anxiety. We investigated the associations between listening and speaking FLA - across behavioral, cognitive, and somatic domains - and participants' resting-state electroencephalography (EEG) signals prior to verbal interactions in a foreign language. The results revealed that significantly higher right-left frontal alpha asymmetry was associated with greater reported FLA in most listening and all of the speaking domains. This study offers insight into the neural processes in connection with FLA, highlighting the significance of frontal alpha asymmetry as a potential neural marker for understanding and addressing its unique challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To track quantitative laryngeal electromyography (LEMG) and voice outcome survey (VOS) changes over 12 months postiatrogenic unilateral vocal fold paralysis (UVFP). To explore the factors influencing these changes., Study Design: Historical cohort study., Setting: Tertiary medical center., Methods: Patients who developed UVFP after surgery underwent a series of assessments, including quantitative LEMG, videolaryngostroboscopy, voice acoustic analysis, and completion of the VOS at diagnosis and at the 12-month follow-up. The subsequent data from these assessments were then compared for analysis. Bivariate analysis examined predictors of changes in VOS and LEMG data respectively, with significant factors further included in a multivariate regression model., Results: The study enrolled 99 patients. LEMG data were prospectively collected within 3.9 months (±SD: 0.2) postsurgery, followed by an average 13.2-month (±SD: 0.2) follow-up. A worse initial turn ratio of thyroarytenoid-lateral cricoarytenoid muscle correlated with more significant subsequent improvement in LEMG findings, reflecting a similar trend observed in the change of VOS scores., Conclusion: This study contributes valuable insights into the temporal change of quantitative LEMG and VOS in patients with iatrogenic UVFP. It suggests that poor initial LEMG and VOS results do not necessarily determine a worse prognosis in terms of electrical activity., (© 2025 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Purpose: Osteoporosis, affecting over 200 million individuals, often remains unrecognized and untreated, increasing the risk of fractures in older adults. Osteoporosis is typically diagnosed with bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). This study aims to develop DeepDXA-Hand, a deep learning model using the efficient CNN-based deep learning architecture, for opportunistic osteoporosis screening from hand radiographs., Methods: DeepDXA-Hand utilizes a CNN-based, HarDNet, approach to predict BMD non-invasively. A total of 10,351 hand radiographs and DXA pairs were used for model training and validation. The model's interpretability was enhanced using GradCAM for hotspot analysis to determine the model's attention areas., Results: The predicted and ground truth BMD were significantly correlated with a correlation coefficient of 0.745. For binary classification of osteoporosis, DeepDXA-Hand demonstrated a sensitivity of 0.73, specificity of 0.83, and accuracy of 0.80, indicating its clinical potential. The model mainly focused on the carpal bones, such as the capitate, trapezoid, hamate, triquetrum, and the head of the second metacarpal bone, suggesting these areas provide radiological features for inferring BMD., Conclusion: DeepDXA-Hand shows potential for the early detection of osteoporosis with high sensitivity and specificity. Further studies should explore its utility in predicting fracture risks., Mini Abstract: Osteoporosis affects millions and often goes undetected and untreated. DeepDXA-Hand, a HarDNet-based deep learning model, predicted bone mineral density with a correlation of 0.745 and classified osteoporosis with 0.80 accuracy. This model enhances early detection and has significant clinical potential as osteoporosis opportunistic screening tool., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yueh-Peng Chen reports financial support was provided by National Science and Technology Council, Taiwan. Yueh-Peng Chen has patent licensed to Yueh-Peng Chen. Chan-Shien Ho has patent issued to Chan-Shien Ho. Tzuo-Yau Fan has patent issued to Tzuo-Yau Fan. Yu-Cheng Pei has patent issued to Yu-Cheng Pei. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Robot-assisted rehabilitation is considered beneficial for functional recovery in patients with stroke, but the therapeutic effect remains inconclusive. The present study investigated the therapeutic effects of gait training assisted by a user-initiated powered exoskeletal robot (UIPER) in patients in the early stage after stroke. We also characterized patients' improvement by analyzing chronological changes in clinical measurements together with gait parameters obtained from internal sensors in the exoskeletal robot., Methods: In this pilot case-controlled study, 17 and 81 patients with stroke onset durations of < 3 months were included in the robot-assisted combined with conventional treatment (RT + CT) group and conventional treatment only (CT) group, respectively. The UIPER, which provides knee flexion and extension support and has hip and knee sensors, was applied to guide gait performance in the RT + CT group. The patients in the RT + CT group received robot-assisted gait training for 40 min/ session, 1 session a day, and 2-3 sessions a week (6 sessions in total). The primary outcome was the proportion of patients reaching the minimum clinically important difference (MCID) in the 5-meter walking speed (5MWS) assessment, and the secondary outcomes were the MCID for the six-minute walking test, the Berg Balance Scale, the Barthel Index, the Fugl-Meyer assessment, and the timed up and go test before, during, and after the interventions. Gait parameters of the hip and knee were evaluated at baseline, midterm, and final sessions., Results: Gait function improved in both groups after the intervention (both P < 0.05). The primary outcome showed that a greater proportion of patients reached the MCID for the 5MWS in the RT + CT group than in the CT group (70.6 vs. 43.2%, P = 0.040; [Formula: see text] = 0.208). Similarly, in terms of the secondary outcomes, more patients in the RT + CT group reached the MCID for the Barthel index as compared with the CT group (41.2 vs. 17.3%, P = 0.047, [Formula: see text] = 0.220). Gait analysis revealed improvements in gait in the RT + CT group, as indicated by increases in the perimeter and area of the hip-knee cyclogram, as well as the range of motion in the hip joint., Conclusions: Gait training assisted by UIPER facilitates the recovery of walking speed and activities of daily living in patients with stroke, and these improvements may be related to improvements in gait parameters. Randomized controlled studies with larger sample sizes are needed to confirm these findings., Trial Registration: This trial was approved by the Institutional Review Board of Chang Gung Medical Foundation (No. 202200822B0)., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of Chang Gung Medical Foundation (No. 202200822B0) on 11th July 2022 and all participants in the present study provided informed consent. Consent for publication: All participants in the present study received instruction about the experimental procedures and content and the experiments were conducted after participants had completed the consent forms. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients., Methods: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients., Results: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05)., Conclusions: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more., (© 2024. The Author(s).)

Objectives: To investigate the causes of space-occupying tumor bed cysts formed early after glioma resection by measuring the osmotic pressure gradient between cystic fluid, serum, and cerebrospinal fluid (CSF) and propose a new method of bedside ultrasound-assisted puncture and drainage (UAP&D) under local anesthesia for treatment., Methods: Bedside UAP&D under local anesthesia was performed through a burr hole on the skull flap.Following a successful puncture, cystic fluid was collected, while blood and CSF were obtained through vein and lumbar puncture, respectively. The osmotic pressure of all fluids collected was measured. The appearance, biochemical composition, and results of microbial culture of cystic fluid and CSF were analyzed. Within 24 h after UAP&D, a CT examination and Glasgow coma scale (GCS) were assessed., Results: The osmotic pressure of cystic fluid was higher than that of serum and CSF. White blood cell count and protein concentration were higher in the cystic fluid compared to the CSF. Conversely, the concentration of chloride ions and glucose were lower. CT scan confirmed the correct placement of the cysts' drainage tube and that the cysts' volume decreased significantly with continued drainage. Accompanied by a reduction in the volume of cysts, there were significant improvements in GCS score within 24 h after UAP&D. All drainage tubes were removed within 2-5 days, and no puncture tract hemorrhage or infection was observed., Conclusion: The osmotic pressure gradient between cystic fluid, serum, and CSF caused the formation of early post-operative space-occupying tumor bed cysts for glioma. UAP&D aligns with the concept that micro-invasive neurosurgery is an effective treatment method for such cysts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Osteoporosis is a common condition that can lead to fractures, mobility issues, and death. Although dual-energy X-ray absorptiometry (DXA) is the gold standard for osteoporosis, it is expensive and not widely available. In contrast, kidney-ureter-bladder (KUB) radiographs are inexpensive and frequently ordered in clinical practice. Thus, it is a potential screening tool for osteoporosis. In this study, we explored the possibility of predicting the bone mineral density (BMD) and classifying high-risk patient groups using KUB radiographs. We proposed DeepDXA-KUB, a deep learning model that predicts the BMD values of the left hip and lumbar vertebrae from an input KUB image. The datasets were obtained from Taiwanese medical centers between 2006 and 2019, using 8913 pairs of KUB radiographs and DXA examinations performed within 6 months. The images were randomly divided into training and validation sets in a 4:1 ratio. To evaluate the model's performance, we computed a confusion matrix and evaluated the sensitivity, specificity, accuracy, precision, positive predictive value, negative predictive value, F1 score, and area under the receiver operating curve (AUROC). Moderate correlations were observed between the predicted and DXA-measured BMD values, with a correlation coefficient of 0.858 for the lumbar vertebrae and 0.87 for the left hip. The model demonstrated an osteoporosis detection accuracy, sensitivity, and specificity of 84.7 %, 81.6 %, and 86.6 % for the lumbar vertebrae and 84.2 %, 91.2 %, and 81 % for the left hip, respectively. The AUROC was 0.939 for the lumbar vertebrae and 0.947 for the left hip, indicating a satisfactory performance in osteoporosis screening. The present study is the first to develop a deep learning model based on KUB radiographs to predict lumbar spine and femoral BMD. Our model demonstrated a promising correlation between the predicted and DXA-measured BMD in both the lumbar vertebrae and hip, showing great potential for the opportunistic screening of osteoporosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53 mut -AURKA amp and endocrine therapy resistance, germline BRCA1 mut -MYC amp and improved sensitivity to PARP inhibitors, and TP53 mut -MYB amp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

(1) Background: This meta-analysis assessed the diagnostic accuracy of deep learning model-based osteoporosis prediction using plain X-ray images. (2) Methods: We searched PubMed, Web of Science, SCOPUS, and Google Scholar from no set beginning date to 28 February 2023, for eligible studies that applied deep learning methods for diagnosing osteoporosis using X-ray images. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. The area under the receiver operating characteristic curve (AUROC) was used to quantify the predictive performance. Subgroup, meta-regression, and sensitivity analyses were performed to identify the potential sources of study heterogeneity. (3) Results: Six studies were included; the pooled AUROC, sensitivity, and specificity were 0.88 (95% confidence interval [CI] 0.85-0.91), 0.81 (95% CI 0.78-0.84), and 0.87 (95% CI 0.81-0.92), respectively, indicating good performance. Moderate heterogeneity was observed. Mega-regression and subgroup analyses were not performed due to the limited number of studies included. (4) Conclusion: Deep learning methods effectively extract bone density information from plain radiographs, highlighting their potential for opportunistic screening. Nevertheless, additional prospective multicenter studies involving diverse patient populations are required to confirm the applicability of this novel technique.

Two-sided coated optical lenses are important in optical applications. A film-stress-induced aberration can adversely affect the lens performance. In this paper, a mechanical method has been developed to reduce this aberration. The proposed method uses a specialized finite element method with an easy modeling process and high versatility to analyze the impact of film parameters (including stress, the thickness, and the coating range) on aberrations under different lens geometric parameters. Theoretically, by selecting the property film parameters within the range of an application's requirements can reduce the aberrations. The proposed method could reduce film-stress-induced aberrations to make the aberration compensation easier.

Background: Emerging evidence has revealed that cricothyroid (CT) muscle dysfunction in unilateral vocal fold paralysis (UVFP) further impairs patients' voices. Given that CT muscle dysfunction does not influence vocal fold position, the mechanism of voice dysfunction induced by dysfunction of CT muscle in UVFP patients remains controversial. This study compares aerodynamics between UVFP patients with and without CT muscle involvement., Methods: This cross-sectional study recruited patients with UVFP manifesting dysphonia, and UVFP was confirmed with videolaryngoscopy and laryngeal electromyography (LEMG). Voice analysis and aerodynamic tests were further performed. Patients with (CT+ group) and without (CT- group) CT muscle involvement were compared., Result: A total of 175 patients (40 in the CT+ group and 135 in the CT- group) with UVFP were analyzed. The CT+ group showed lower maximal sound pressure level (SPL) (P=0.039), mean SPL (P=0.042), peak air pressure (P<0.001), mean peak air pressure (P<0.001) and aerodynamic power (P=0.004) than the CT- group., Conclusion: The decrease in SPL, peak air pressure, and aerodynamic power in UVFP patients with CT muscle dysfunction suggests that the effect of CT muscle dysfunction is mediated by a change in aerodynamics., Competing Interests: Conflict of interest None., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Germline-somatic mutation interactions are universal and associated with tumorigenesis, but their role in breast cancer, especially in non-Caucasians, remains poorly characterized. We performed large-scale prospective targeted sequencing of matched tumor-blood samples from 4079 Chinese females, coupled with detailed clinical annotation, to map interactions between germline and somatic alterations. We discovered 368 pathogenic germline variants and identified 5 breast cancer DNA repair-associated genes (BCDGs; BRCA1/BRCA2/CHEK2/PALB2/TP53). BCDG mutation carriers, especially those with two-hit inactivation, demonstrated younger onset, higher tumor mutation burden, and greater clinical benefits from platinum drugs, PARP inhibitors, and immune checkpoint inhibitors. Furthermore, we leveraged a multiomics cohort to reveal that clinical benefits derived from two-hit events are associated with increased genome instability and an immune-activated tumor microenvironment. We also established an ethnicity-specific tool to predict BCDG mutation and two-hit status for genetic evaluation and therapeutic decisions. Overall, this study leveraged the large sequencing cohort of Chinese breast cancers, optimizing genomics-guided selection of DNA damaging-targeted therapy and immunotherapy within a broader population., (© 2023. The Author(s).)

Objectives: Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal fold paralysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFP patients to investigate the pathophysiologic mechanisms of UVFP., Methods: In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measured using B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode., Results: Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA) muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respectively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side, as observed through LEMG, correlated with the VF length during the resting phase (R=0.368, P=0.050) and CDVL values (R=0.627, P=0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlated with the normalized phonatory vocal length change (nPLC; R=0.621, P=0.041) on the paralyzed side., Conclusion: CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFP cases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The findings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngeal nerve injury and offer valuable insights into the pathophysiology of UVFP.

Aims: Glioblastoma multiforme (GBM) is the deadliest glioma and its resistance to temozolomide (TMZ) remains intractable. Long non-coding RNAs (lncRNAs) play crucial roles in that and this study aimed to investigate underlying mechanism of HOXD-AS2-affected temozolomide sensitivity in glioblastoma., Methods: We analyzed and validated the aberrant HOXD-AS2 expression in glioma specimens. Then we explored the function of HOXD-AS2 in vivo and in vitro and a clinical case was also reviewed to examine our findings. We further performed mechanistic experiments to investigate the mechanism of HOXD-AS2 in regulating TMZ sensitivity., Results: Elevated HOXD-AS2 expression promoted progression and negatively correlated with prognosis of glioma; HOXD-AS2 attenuated temozolomide sensitivity in vitro and in vivo; The clinical case also showed that lower HOXD-AS2 sensitized glioblastoma to temozolomide; STAT3-induced HOXD-AS2 could interact with IGF2BP2 protein to form a complex and sequentially upregulate STAT3 signaling, thus forming a positive feedback loop regulating TMZ sensitivity in glioblastoma., Conclusion: Our study elucidated the crucial role of the HOXD-AS2-STAT3 positive feedback loop in regulating TMZ sensitivity, suggesting that this could be provided as a potential therapeutic candidate of glioblastoma., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Background: Walking entails orchestration of the sensory, motor, balance, and coordination systems, and walking disability is a critical concern after stroke. How and to what extent these systems influence walking disability after stroke and recovery have not been comprehensively studied., Methods: We retrospectively analyzed patients with stroke in the Post-acute care-Cerebrovascular Diseases (PAC-CVD) program. We compared the characteristics of patient groups stratified by their ability to complete the 5-m walk test across various time points of rehabilitation. We then used stepwise linear regression to examine the degree to which each stroke characteristic and functional ability could predict patient gait performance., Results: Five hundred seventy-three patients were recruited, and their recovery of walking ability was defined by the timing of recovery in a 5-m walk test. The proportion of patients who could complete the 5-m walk test at admission, at 3 weeks of rehabilitation, at 6 weeks of rehabilitation, between 7 and 12 weeks of rehabilitation, and who could not complete the 5-m walk test after rehabilitation was 52.2%, 21.8%, 8.7%, 8.7%, and 8.6%, respectively. At postacute care discharge, patients who regained walking ability earlier had a higher chance of achieving higher levels of walking activity. Stepwise linear regression showed that Berg Balance Scale (BBS) (β: 0.011, p < .001), age (β: -0.005, p = .001), National Institutes of Health Stroke Scale (NIHSS) (6a + 6b; β: -0.042, p = .018), Mini-Nutritional assessment (MNA) (β: -0.007, p < .027), and Fugl-Meyer upper extremity assessment (FuglUE) (β: 0.002, p = .047) scores predicted patient's gait speed at discharge., Conclusion: Balance, age, leg strength, nutritional status, and upper limb function before postacute care rehabilitation are predictors of walking performance after stroke., Competing Interests: Conflicts of interest None., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Touch is a crucial sense for perceiving the spatial characteristics of objects. The JVP dome was developed to evaluate tactile spatial acuity using a grating orientation task. There were few studies depicting sequences and details for the entire task, including practice, training, and testing sessions. Therefore, we proposed and elaborated a protocol for the grating orientation task using the staircase method, which required fewer testing trials compared with the method of constant stimuli., Methods: Twenty-three healthy participants were enrolled in this experiment. The JVP domes with 11 different groove widths were used. Tactile discrimination thresholds were estimated using a two-down-one-up staircase method. The experiment comprised practice, training, and testing sessions, conducted by trained examiners who performed grating stimulation on participants' index fingerpads., Results: All participants passed the required accuracy in the practice and training sessions. Eight transition points were obtained in the testing session for each participant. The tactile discrimination thresholds were determined from the last six transition points. We obtained the mean tactile discrimination threshold as 1.8 ± 0.75 mm (n = 23). The results demonstrated that the proposed protocol was successfully applied to assess tactile discrimination thresholds., Conclusions: The present study investigated the protocol of grating orientation tasks requiring a small number of testing trials with the assurance of the task quality. The feasibility study and preliminary results indicated the potentiality of this protocol for future clinical application., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Dysregulation of RNA-binding proteins (RBP) is one of the characteristics of cancer. Investigating the biological functions and molecular mechanisms of abnormal RBPs can help uncover new cancer biomarkers and treatment strategies. To identify oncogenic RBPs in triple-negative breast cancer (TNBC), we employed an in vivo CRISPR screen and a TNBC progression model, which revealed small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator of TNBC progression. SNRPC was frequently upregulated, which corresponded to poor prognosis in patients with TNBC. SNRPC ablation significantly impaired the proliferation, migration, and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II-controlled transcriptional program. Knockdown of SNRPC decreased RNA Pol II enrichment on a subset of oncogenes (TNFAIP2, E2F2, and CDK4) and reduced their expression levels. Furthermore, SNRPC deletion was confirmed to inhibit TNBC progression partially through regulation of the TNFAIP2-Rac1-β-catenin signaling pathway. Taken together, this data suggests that SNRPC plays an oncogenic role in TNBC, is a marker of poor prognosis, and may be a valuable therapeutic target for patients with intractable TNBC., Significance: A functional CRISPR screen identifies SNRPC as an RNA-binding protein that promotes the aggressiveness of breast cancer by facilitating Pol II-controlled transcription of oncogenes., (©2023 American Association for Cancer Research.)

Several methods for the measurement of tactile acuity have been devised previously, but unexpected nonspatial cues and intensive manual skill requirements compromise measurement accuracy. Therefore, we must urgently develop an automated, accurate, and noninvasive method for assessing tactile acuity. The present study develops a novel method applying a robotic tactile stimulator to automatically measure tactile acuity that comprises eye-opened, eye-closed training, and testing sessions. Healthy participants judge the orientation of a rotating grating ball presented on their index fingerpads in a two-alternative forced-choice task. A variable rotation speed of 5, 10, 40, or 160 mm/s was used for the tactile measurement at a variety of difficulties. All participants met the passing criteria for the training experiment. Performance in orientation identification, quantified by the proportion of trials with correct answers, differed across scanning directions, with the highest rotation speed (160 mm/s) having the worst performance. Accuracy did not differ between vertical and horizontal orientations. Our results demonstrated the utility of the pre-test training protocol and the functionality of the developed procedure for tactile acuity assessment. The novel protocol performed well when applied to the participants. Future studies will be conducted to apply this method to patients with impairment of light touch.

Due to environmental interference and defects in measured objects, measurement signals are frequently affected by unpredictable noise and periodic defects. Moreover, there is a lack of effective methods for accurately distinguishing defect components from measurement signals. In this study, a distribution-based selective optimisation method (SOM) is proposed to mitigate the effects of noise and defect components. The SOM can be seen as a binary- or multiple-class signal classifier based on an error distribution, which can simultaneously eliminate periodic defect components of measurement signals and proceed with signal-fitting regression. The effectiveness, accuracy, and feasibility of the SOM are verified in theoretical and realworld measurement settings. Based on theoretical simulations under various parameter conditions, some criteria for selecting operation variables among a selection of parameter conditions are explained in detail. The proposed method is capable of separating defect components from measurement signals while also achieving a satisfactory fitting curve for the measurement signals. The proposed SOM has broad application prospects in signal processing and defect detection for mechanical measurements, electronic filtering, instrumentation, part maintenance, and other fields., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Intracranial fungal infection is a rare condition that often requires surgical intervention. In this study, we present a case of intracranial fungal infection with a space-occupying effect and a long medical history of five years. We comprehensively evaluated the medical history, symptoms, imaging manifestations, and pathological examinations of the patient to confirm this rare case of fungal infection with cyst formation. Moreover, we reviewed the literature on intracranial fungal infection, hoping to draw awareness and attention to this rare disease.

Background: Stroke and spinal cord injury are neurological disorders that cause disability and exert tremendous social and economic effects. Robot-assisted training (RAT), which may reduce spasticity, is widely applied in neurorehabilitation. The combined effects of RAT and antispasticity therapies, such as botulinum toxin A injection therapy, on functional recovery remain unclear. This review evaluated the effects of combined therapy on functional recovery and spasticity reduction., Materials and Methods: Studies evaluating the efficacy of RAT and antispasticity therapy in promoting functional recovery and reducing spasticity were systemically reviewed. Five randomized controlled trials (RCTs) were included. The modified Jadad scale was applied for quality assessment. Functional assessments, such as the Berg Balance Scale, were used to measure the primary outcome. Spasticity assessments, such as the modified Ashworth Scale, were used to measure the secondary outcome., Results: Combined therapy improves functional recovery in the lower limbs but does not reduce spasticity in the upper or lower limbs., Conclusions: The evidence supports that combined therapy improves lower limb function but does not reduce spasticity. The considerable risk of bias among the included studies and the enrolled patients who did not receive interventions within the golden period of intervention are two major factors that should be considered when interpreting these results. Additional high-quality RCTs are required.

Unilateral vocal fold paralysis (UVFP) causes glottal incompetence and poor vocal efficiency. The influence of laryngeal neuromuscular control on aerodynamics in UVFP remains unclear. This study investigated the relationship between laryngeal muscle activities using quantitative laryngeal electromyography (LEMG) and aerodynamics in UVFP. This prospective study recruited patients with UVFP, and the diagnosis was confirmed with videolaryngostroboscopy and LEMG. The patient received aerodynamic assessment and LEMG of the thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex and the cricothyroid (CT) muscle. The relationship between quantitative LEMG and aerodynamic parameters was analyzed. A total of 134 UVFP patients without concurrent CT muscle involvement were enrolled. Compared with the normal side, the peak turn frequency of the lesioned side was lower in the TA-LCA (p < 0.001) and CT (p = 0.048) muscles. Stepwise linear regression revealed that the turn ratio of TA-LCA muscles was a robust factor in the decrease in peak expiratory airflow (β = −0.34, p = 0.036), mean airflow during voicing (β = −0.28, p = 0.014), and aerodynamic power (β = −0.42, p = 0.019), and an increase in aerodynamic efficiency (β = 27.91, p = 0.012). In addition, the turn ratio of CT muscles was a potent factor in inducing an increase in aerodynamic resistance (β = 14.93, p = 0.029). UVFP without CT involvement still showed suppression of CT muscles on the lesioned side, suggesting that neurological impairment of the TA-LCA complex could cause asymmetrical compensation of CT muscles, further impeding aerodynamics. The residual function of TA-LCA muscle complexes facilitates less air leakage and power dissipation, enhancing aerodynamic efficiency. On the other hand, the symmetrical compensation of the CT muscles improves aerodynamic resistance.

Bi-manual therapy (BT), mirror therapy (MT), and robot-assisted rehabilitation have been conducted in hand training in a wide range of stages in stroke patients; however, the mechanisms of action during training remain unclear. In the present study, participants performed hand tasks under different intervention conditions to study bilateral sensorimotor cortical communication, and EEG was recorded. A multifactorial design of the experiment was used with the factors of manipulating objects (O), robot-assisted bimanual training (RT), and MT. The sum of spectral coherence was applied to analyze the C3 and C4 signals to measure the level of bilateral corticocortical communication. We included stroke patients with onset <6 months (n = 6), between 6 months and 1 year (n = 14), and onset >1 year (n = 20), and their Brunnstrom recovery stage ranged from 2 to 4. The results showed that stroke duration might influence the effects of hand rehabilitation in bilateral cortical corticocortical communication with significant main effects under different conditions in the alpha and beta bands. Therefore, stroke duration may influence the effects of hand rehabilitation on interhemispheric coherence.

In this cross-sectional study, we compared voice tone and activities relating to the laryngeal muscle between unilateral vocal fold paralysis (UVFP) patients with and without cricothyroid (CT) muscle dysfunction to define how CT dysfunction affects language tone. Eighty-eight female surgery-related UVFP patients were recruited and received acoustic voice analysis and laryngeal electromyography (LEMG) when the patient was producing the four Mandarin tones. The statistical analysis was compared between UVFP patients with (CT+ group, 17 patients) and without CT muscle (CT- group, 71 patients) involvement. When producing Mandarin Tone 2, the voice tone in the CT+ group had smaller rise range ( p = 0.007), lower rise rate ( p = 0.002), and lower fundamental frequency (F0) at the offset point of the voice ( p = 0.023). When producing Mandarin Tone 4, the voice tone in the CT+ group had smaller drop range ( p = 0.019), lower drop rate ( p = 0.005), and lower F0 at voice onset ( p = 0.025). The CT+ group had significantly lower CT muscle activity when producing the four Mandarin tones. In conclusion, CT dysfunction causes a limitation of high-rising tone in Tone 2 and high-falling tone in Tone 4, a property that dramatically limits the tonal characteristics in Mandarin, a tonal language. This limitation could further impair the patient's communication ability.

Background: Unilateral vocal fold paralysis (UVFP) affects the glottal gap, voice, and aerodynamics, whereas injection laryngoplasty (IL) using hyaluronate is an effective treatment for UVFP by decreasing the glottal gap to improve voice. Previous studies have shown that the involvement of cricothyroid (CT) muscle in UVFP patients further affects patients' aerodynamics, but it remains unclear whether the difference remains after IL. This study investigates whether the aerodynamic features observed in UVFP with CT involvement could still be observed after IL., Methods: This study recruited UVFP patients with dysphonia, and IL was performed within 6 months of initial symptoms. All subjects received assessments including videolaryngoscopy, voice analysis, and aerodynamics at three time points: before IL, 1 month after IL, and 6 months after IL. The glottal gap, voice, and aerodynamics between patients with and without CT involvement (the CT+ and CT- groups) were compared, and the change (Δ) before and after IL and repeated-measures analysis of variance (ANOVA) were also compared between the two groups., Result: A total of 71 patients with UVFP (22 in the CT+ group and 49 in the CT- group) were analyzed. After IL, the CT+ group showed a lower sound pressure level (SPL), higher Δair pressure, and smaller Δaerodynamic power than the CT- group., Conclusion: The CT+ group had a lower SPL, even after elevating air pressure to attempt to achieve a higher vocal intensity. The results suggest that although closure of the glottal gap was achieved by IL, the CT+ group still had a lower loudness and needed to sustain a higher peak air pressure when producing voice., Level of Evidence: Level 4., Competing Interests: The authors declare that they have no conflicts of interests., (© 2022 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Study Design: A randomized controlled pilot study., Background: Bimanual therapy (BMT) is an effective neurorehabilitation therapy for the upper limb, but its application to the distal upper limb is limited due to methodological difficulties. Therefore, we applied an exoskeleton hand to perform robot-assisted task-oriented bimanual training (RBMT) in patients with stroke., Objective: To characterize the effectiveness of RBMT in patients with hemiplegic stroke with upper limb motor impairment., Interventions: A total of 19 patients with subacute stroke (1-6 months from onset) were randomized and allocated to RBMT and conventional therapy (CT) groups. The RBMT and CT groups received 90 min of training/day (RBMT: 60 min RBMT + 30 min CT; CT: 60 min CT for hand functional training + 30 min regular CT), 5 days/week, for 4 weeks (20 sessions during the experimental period)., Assessments: Clinical assessments, including the Fugl-Meyer assessment of the upper extremity (FMA-UE), action research arm test (ARAT), and wolf motor arm function test (WMFT), were conducted before and after the intervention., Results: Within-group analysis showed a significant improvement in the FMA-UE and WMFT in both the CT and RBMT groups. A significant improvement in the Fugl-Meyer assessment (FMA) of the wrist and hand for the distal part in the RBMT group occurred earlier than that in the CT group. A significant improvement in WMFT time was found in both groups, but the WMFT functional ability assessment was only found in the RBMT group. No significant improvements in ARAT assessment were observed in either the CT or RBMT groups. Compared with CT, significant improvements were found in terms of the proportion of minimally clinically important differences after RBMT in FMA-UE (χ 2 = 4.34, p = 0.037). No adverse events were reported by any of the participants across all sessions., Conclusions: This study is the first to apply RBMT to the distal part of the upper limb. Both RBMT and CT are effective in improving the upper limb function in patients with subacute stroke. RBMT shows superior potential efficacy in facilitating recovery of the distal part of upper extremity (UE) motor function in the early stage. Future randomized control studies with a large sample size and follow-up assessments are needed to validate the present conclusions., Competing Interests: J-JH is the designer of the Mirror Hand and the funder of Rehabotics Medical Technology, Taiwan. The remaining 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 © 2022 Ma, Li, Xu, Yang, Feng, Wang, Huang, Pei and Pan.)

Immune checkpoint inhibitors exhibit limited response rates in patients with triple-negative breast cancer (TNBC), suggesting that additional immune escape mechanisms may exist. Here, we performed two-step customized in vivo CRISPR screens targeting disease-related immune genes using different mouse models with multidimensional immune-deficiency characteristics. In vivo screens characterized gene functions in the different tumor microenvironments and recovered canonical immunotherapy targets such as Ido1 . In addition, functional screening and transcriptomic analysis identified Lgals2 as a candidate regulator in TNBC involving immune escape. Mechanistic studies demonstrated that tumor cell-intrinsic Lgals2 induced the increased number of tumor-associated macrophages, as well as the M2-like polarization and proliferation of macrophages through the CSF1/CSF1R axis, which resulted in the immunosuppressive nature of the TNBC microenvironment. Blockade of LGALS2 using an inhibitory antibody successfully arrested tumor growth and reversed the immune suppression. Collectively, our results provide a theoretical basis for LGALS2 as a potential immunotherapy target in TNBC.

Pain assessment is essential for preclinical and clinical studies on pain. The mouse grimace scale (MGS), consisting of five grimace action units, is a reliable measurement of spontaneous pain in mice. However, MGS scoring is labor-intensive and time-consuming. Deep learning can be applied for the automatic assessment of spontaneous pain. We developed a deep learning model, the DeepMGS, that automatically crops mouse face images, predicts action unit scores and total scores on the MGS, and finally infers whether pain exists. We then compared the performance of DeepMGS with that of experienced and apprentice human scorers. The DeepMGS achieved an accuracy of 70-90% in identifying the five action units of the MGS, and its performance (correlation coefficient = 0.83) highly correlated with that of an experienced human scorer in total MGS scores. In classifying pain and no pain conditions, the DeepMGS is comparable to the experienced human scorer and superior to the apprentice human scorers. Heatmaps generated by gradient-weighted class activation mapping indicate that the DeepMGS accurately focuses on MGS-relevant areas in mouse face images. These findings support that the DeepMGS can be applied for quantifying spontaneous pain in mice, implying its potential application for predicting other painful conditions from facial images.

Importance: Baseline global cognitive function may affect cognitive and functional outcomes during combined physical and cognitive training; however, how it influences the effects of combined training remains uncertain., Objective: To determine the impact of baseline global cognitive function on cognitive and functional outcomes after combined physical and cognitive training among older adults with cognitive decline., Design: Observational., Setting: Local communities and senior centers., Participants: Older adults with mild cognitive decline (MCD; n = 51) and moderate to severe cognitive decline (MSCD; n = 40)., Intervention: Participants received 45 to 55 min of physical exercise training followed by 45 to 55 min of cognitive training in one session per week for 12 wk. Outcomes and Measures: Montreal Cognitive Assessment (MoCA), Lawton-Brody Instrumental Activities of Daily Living Scale (Lawton-Brody IADL), Word Recall Test (WRT), Stroop Color and Word Test (SCWT), Digital Symbol Substitution Test (DSST), and Trail Making Test (TMT) scores were assessed and compared between the MCD and MSCD groups., Results: Significant interaction effects were found for the WRT, SCWT, MoCA, and Lawton-Brody IADL. WRT and SCWT scores significantly improved in the MCD group, whereas MoCA and Lawton-Brody IADL scores significantly improved in the MSCD group. DSST scores increased among all participants, but TMT scores improved only in the MCD group., Conclusions and Relevance: Older adults' baseline global cognitive function affected cognitive and instrumental activities of daily living (IADL) outcomes regarding combined training. High-level cognitive function, including inhibition and shifting abilities and working memory capacity, improved among older adults with MCD, whereas general cognitive function and IADLs improved among older adults with MSCD. What This Article Adds: Findings revealed domain-specific changes with respect to baseline cognitive function, which may help to refine current combined training protocols and facilitate development of personalized combined training programs for older adults with cognitive impairments., (Copyright © 2022 by the American Occupational Therapy Association, Inc.)

Background: To compare the immediate effectiveness of low-level laser therapy (LLLT) applied to classical acupoints versus trigger points for patients with cervical myofascial pain syndrome (MPS)., Methods: This was a single-blinded, randomized, placebo-controlled trial. This study was performed in a university-affiliated medical center. One hundred participants with cervical myofascial pain syndrome were randomly allocated to four treatment groups, including (1) acupoint therapy (AcuT), (2) acupoint control (AcuC), (3) trigger point therapy (TriT), and (4) trigger point control (TriC) groups. Low-level laser (810-nm) therapy was used in both therapy groups, while the same procedure was performed without laser in the acupoint control groups. The patients were evaluated based on visual analogue scale (VAS) pain score, pressure pain threshold, and cervical range of motion (ROM) before and after the therapy., Results: Immediate pain relief was observed in the TriT group (p < 0.01). The TriT group showed improved cervical ROM in ipsilateral bending (p < 0.01), while the AcuT group did not., Conclusions: LLLT applied to trigger points could significantly relieve myofascial pain and was effective in relieving cervical ROM limitations. Considering the risk of pneumothorax, laser therapy at trigger points for patients with cervical MPS may be a choice when acupuncture therapy is unavailable., Trial Registration: ClinicalTrials.gov ID: NCT01516502., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Unilateral vocal fold paralysis (UVFP) caused by lung surgery is associated with prolonged hospital stay and increased postoperative comorbidities. We evaluated lung surgery-related UVFP and compared its characteristics with UVFP caused by esophageal and thyroid surgeries, as the most common surgical causes of UVFP. We also evaluated the outcomes of intracordal hyaluronate injection laryngoplasty in these patients., Methods: Patients with surgery-related UVFP were evaluated by quantitative laryngeal electromyography, videolaryngostroboscopy, voice acoustic analysis, Voice Outcome Survey (VOS) questionnaire, and Short Form-36 Health Survey (SF-36) quality-of-life questionnaire. Data for the lung, esophageal, and thyroid surgery groups were compared and changes in outcome measurements induced by hyaluronate injection were compared among the three groups., Results: A total of 141 patients were recruited, including 21, 46, and 74 in the lung, esophageal, and thyroid surgery groups, respectively. Compared with the other two groups, lung surgery patients had predominantly left-sided UVFP, less involvement of the external branch of the superior laryngeal nerve, and higher jitter. Most outcome measurements improved in all three groups after office-based hyaluronate injection, with the greatest improvement in jitter in the lung surgery group., Conclusions: Lung surgery-related UVFP showed a distinct disease presentation, and patients' voice parameters and quality of life recovered dramatically after office-based hyaluronate injection. We recommend evaluation of lung surgery-related UVFP and early intervention, such as office-based hyaluronate injection, to improve patients' voice function and quality of life., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Early injection laryngoplasty (EIL) using hyaluronic acid (HA) is an effective treatment for glottic insufficiency in patients with acute unilateral vocal fold paralysis (UVFP). Most patients benefit by showing improvement in voice and quality of life and implied reduced need for permanent laryngoplasty. However, injected HA might resolve within a short period, so its long-term outcomes and the need for secondary procedures need to be clarified., Methods: Patients who underwent EIL with HA for acute UVFP from January 2015 to December 2018 were included. The factors that may associate with the prognosis including voice performance and laryngeal configuration at presentation, the cause of UVFP, and the type of HA for EIL were analyzed., Results: Ninety-four patients were included for analysis, with a mean follow-up period of 25.1 months (95% CI: 22.8-27.4 months). After primary HA injection, 22 patients (23.4%) underwent secondary procedures (rate: 13.1% per person-year), and most (63.6%) of the events occurred after one year from the first injection. The rate of secondary procedures within the first 12 months was 9.0% (14.1% and 4.3% for low-concentrated HA (LHA) and high-concentrated HA (HHA), respectively). The incidence of the secondary procedures was higher in the LHA group (18.2%) ( p = 0.026) than in the HHA group (7.5%)., Conclusions: The rate of secondary procedures was lower than the prediction based on the resorption time of HA, a finding that could be partly accounted for by both natural nerve recovery and a long-lasting effect of EIL. EIL with HHA had a lower rate of re-treatment than that with LHA, suggesting a better clinical utility for acute UVFP.

DeepDXA is a deep learning model designed to infer bone mineral density data from plain pelvis X-ray, and it can achieve good predicted value for clinical use., Purpose: Osteoporosis is defined as a systemic disease of the bone characterized by a decrease in bone strength and deterioration of bone structure at the microscopic level, leading to bone fragility and increased risk of fracture. Bone mineral density (BMD) is the preferred method for the diagnosis of osteoporosis, and dual-energy x-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis. Conventional radiography is more suited for the screening of osteoporosis rather than diagnosis, and osteoporosis can be detected on radiographs by experienced physicians only. This study explored the possibility of predicting BMD relative to DXA using patient radiographs., Methods: A deep learning algorithm of convolutional neural network (CNN) was used for the purpose. The method includes image segmentation, CNN learning, and a convolution-based regression model (DeepDXA) that links the isolated images of the femur bone to predict BMD value. Data were obtained in a single medical center from 2006 to 2018, with a total amount of 3472 pairs of pelvis X-ray and DXA examination within 1 year., Results: The proposed workflow successfully predicted BMD values of the femur bone with the correlation coefficient (R) of 0.85 (P < 0.001) and the accuracy of 0.88 for prediction osteoporosis, a finding that could be reliably ready for further clinical use., Conclusion: When suspicious osteoporosis is seen on plain films using the deep learning method we developed, further referral to DXA for the definite diagnosis of osteoporosis is indicated., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Prediction of post-stroke functional outcomes is crucial for allocating medical resources. In this study, a total of 577 patients were enrolled in the Post-Acute Care-Cerebrovascular Disease (PAC-CVD) program, and 77 predictors were collected at admission. The outcome was whether a patient could achieve a Barthel Index (BI) score of >60 upon discharge. Eight machine-learning (ML) methods were applied, and their results were integrated by stacking method. The area under the curve (AUC) of the eight ML models ranged from 0.83 to 0.887, with random forest, stacking, logistic regression, and support vector machine demonstrating superior performance. The feature importance analysis indicated that the initial Berg Balance Test (BBS-I), initial BI (BI-I), and initial Concise Chinese Aphasia Test (CCAT-I) were the top three predictors of BI scores at discharge. The partial dependence plot (PDP) and individual conditional expectation (ICE) plot indicated that the predictors' ability to predict outcomes was the most pronounced within a specific value range (e.g., BBS-I < 40 and BI-I < 60). BI at discharge could be predicted by information collected at admission with the aid of various ML models, and the PDP and ICE plots indicated that the predictors could predict outcomes at a certain value range.

Paired stimulation has been applied to modulate neuronal functions in the primary somatosensory cortex but its utility in the alternation of tuning function, such as direction tuning for whisker stimuli, remains unclear. In the present study, we attempted to manipulate feature preferences in barrel cortical neurons using repetitive paired whisker deflection combined with optogenetic stimulation and to obtain optimal parameters that can induce neuroplasticity. We found no significant response changes across stimulus parameters, such as onset asynchronies and paired directions. Only when paired stimulation was applied in the nonpreferred direction of the principal whisker of a neuron, were the neuron's responses enhanced in that direction. Importantly, this effect was only observed when the optogenetic stimulus preceded the mechanical stimulus. Our findings indicate that repetitive paired optogenetic-mechanical stimulation can induce in vivo neuroplasticity of feature selectivity in limited situations., 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 © 2021 Cheng, Huang, Yeh and Pei.)

Background: The germline variant spectrum of triple-negative breast cancer (TNBC) is different from that of other subtypes and has demonstrated ethnic differences. However, the germline variants of TNBC among Chinese patients and its clinical significance remain unclear., Methods: Using our multi-omics TNBC cohort (n = 325), we determined the spectrum of germline variants in TNBC and aimed to illustrate their biological and clinical implications., Results: Overall, 16.0% (52 of 325) of TNBC patients harbored at least 1 pathogenic or likely pathogenic germline variant. These germline variants were associated with early onset of TNBC, the occurrence of contralateral breast cancer, the basal-like immune-suppressed mRNA subtype, and the homologous recombination deficiency (HRD) mutation subtype. Somatic allele-specific imbalance was observed in 54.1% of these germline variants, which was correlated with early onset of breast cancer and elevated HRD. The genes BRCA1 (7.4%), RAD51D (2.8%), and BRCA2 (2.2%) were those most frequently mutated. The RAD51D germline variants, especially K91fs, were enriched in Chinese patients with TNBC compared with Caucasian and African American patients. The Chinese-specific RAD51D germline variants were functionally associated with the instability of the RAD51D protein, HRD, and sensitivity to PARP inhibitors., Conclusions: Chinese TNBC patients have a distinct spectrum of germline variants, with a remarkable impact on the clinical and molecular characteristics of the tumor. Integrative germline-somatic analysis may help identify TNBC patients who are most likely to be affected by their germline variants and in performing clinical interventions more precisely. The RAD51D variants enriched in our cohort may serve as therapeutic targets and guide precision treatment of TNBC., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The mechanism of the deactivation and regeneration of PtSn intermetallic compound nanoparticle (iNP) catalysts was studied by in situ TEM investigation. Our study reveals the reversible dynamic structural transition of the iNPs during deactivation and regeneration, which provides a direct correlation between the atomic structure and the catalytic activity of the iNPs.

Objective: Traditionally, after total laryngopharyngectomy (TLP), patients cannot speak without a prosthesis or an artificial larynx. In Taiwan, most patients use a commercialized pneumatic laryngeal device (PLD). Phonatory tube reconstruction with the anterolateral thigh (ALT) flap is a novel, modified version of synchronous digestive and phonatory reconstruction involving a free muscular cutaneous flap. This study reviewed and compared speech performance between patients who underwent novel flap reconstruction and conventional PLD users., Method: We retrospectively reviewed patients with laryngeal or hypopharyngeal cancer who underwent TLP from August 2017 to September 2019. The voice handicap index (VHI), speech intelligibility, acoustic and aerodynamic analysis results, and speech range profile (SRP) were compared between patients who underwent ALT phonatory tube reconstruction (ALT group) and those using PLDs (PLD group)., Results: Twenty patients were included; 13 patients were included in the ALT group, and 7 patients were included in the PLD group. Compared to the PLD group, the ALT group had a better fundamental frequency range (P < .001) and semitone range (P < .001) during speech but showed worse jitter, shimmer, and harmonic-to-noise ratios. The two groups showed comparable VHI and speech intelligibility performance., Conclusions: The ALT phonatory tube, a novel flap for reconstruction, can restore digestive and voice functions simultaneously. Compared with PLD use, ALT phonatory tube reconstruction yields an improved speech range and comparable levels of voice handicap and speech intelligibility, suggesting that the technique is a good alternative for patients after TLP., Level of Evidence: 4 Laryngoscope, 131:1349-1357, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

(1) Background: severe weight loss was reported to be related to unilateral vocal fold paralysis (UVFP) after esophagectomy and could thus impair survival. Concomitant radical lymph node dissection along the recurrent laryngeal nerve during esophageal cancer surgery is controversial, as it might induce UVFP. Early intervention for esophagectomy-related UVFP by administering intracordal injections of temporal agents has recently become popular. This study investigated the survival outcomes of esophagectomy for esophageal squamous cell carcinoma (ESCC) after the introduction of early injection laryngoplasty (EIL). (2) Methods: a retrospective review of patients with ESCC after curative-intent esophagectomy was conducted in a tertiary referral medical center. The necessity of EIL with hyaluronic acid was comprehensively discussed for all symptomatic UVFP patients. The survival outcomes and related risk factors of ESCC were evaluated. (3) Results: among the cohort of 358 consecutive patients who underwent esophagectomy for ESCC, 42 (11.7%) showed postsurgical UVFP. Twenty-nine of them received office-based EIL. After EIL, the glottal gap area, maximum phonation time and voice outcome survey showed significant improvement at one, three and six months measurements. The number of lymph nodes in the resected specimen was higher in those with UVFP than in those without UVFP (30.1 ± 15.7 vs. 24.6 ± 12.7, p = 0.011). The Kaplan-Meier overall survival was significantly better in patients who had UVFP ( p = 0.014), received neck anastomosis ( p = 0.004), underwent endoscopic resection ( p < 0.001) and had early-stage cancer ( p < 0.001). Multivariate Cox logistic regression analysis showed two independent predictors of OS, showing that the primary stage and anastomosis type are the two independent predictors of OS. (4) Conclusion: EIL is effective in improving UVFP-related symptoms, thus providing compensatory and palliative measures to ensure the patient's postsurgical quality of life. The emerging use of EIL might encourage cancer surgeons to radically dissect lymph nodes along the recurrent laryngeal nerve, thus changing the survival trend.

Triple-negative breast cancer (TNBC) remains an unmet medical challenge. We investigated metabolic dysregulation in TNBCs by using our multi-omics database (n = 465, the largest to date). TNBC samples were classified into three heterogeneous metabolic-pathway-based subtypes (MPSs) with distinct metabolic features: MPS1, the lipogenic subtype with upregulated lipid metabolism; MPS2, the glycolytic subtype with upregulated carbohydrate and nucleotide metabolism; and MPS3, the mixed subtype with partial pathway dysregulation. These subtypes were validated by metabolomic profiling of 72 samples. These three subtypes had distinct prognoses, molecular subtype distributions, and genomic alterations. Moreover, MPS1 TNBCs were more sensitive to metabolic inhibitors targeting fatty acid synthesis, whereas MPS2 TNBCs showed higher sensitivity to inhibitors targeting glycolysis. Importantly, inhibition of lactate dehydrogenase could enhance tumor response to anti-PD-1 immunotherapy in MPS2 TNBCs. Collectively, our analysis demonstrated the metabolic heterogeneity of TNBCs and enabled the development of personalized therapies targeting unique tumor metabolic profiles., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Multiple glioblastoma multiforme (GBM) is classified as multifocal and multicentric GBM according to whether there is communication between the lesions. Multiple GBM is more genetically heterogeneous, aggressive and resistant to chemoradiotherapy than unifocal GBM, and has a worse prognosis. There is no international consensus on the treatment of multiple GBM. This review discusses some paradigms of multiple GBM and focuses on the heterogeneity spread pathway, imaging diagnosis, pathology, molecular characterization and prognosis of multifocal and multicentric GBM. Several promising therapeutic methods of multiple GBM are also recommended., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

Background: Iatrogenic unilateral vocal fold paralysis caused by thyroid surgery induces profound physical and psychosocial distress in patients. The natural course of functional recovery over time differs substantially across subjects, but the mechanisms underlying this difference remain unclear. In this study, we examined whether the anatomic site of the lesion affected the trajectory of recovery., Methods: In this prospective case series study in a single medical center, patients with thyroid surgery-related unilateral vocal fold paralysis were evaluated using quantitative laryngeal electromyography, videolaryngostroboscopy, voice acoustic analysis, the Voice Outcome Survey, and the Short Form-36 quality-of-life questionnaire. Patients with and without superior laryngeal nerve injuries were compared., Results: Forty-two patients were recruited, among whom 15 and 27 were assigned to the with and without superior laryngeal nerve injury groups, respectively. Compared with the group without superior laryngeal nerve injury, the group with superior laryngeal nerve injury group demonstrated less improvement in the recruitment of vocal fold adductors, and the group also had more severe impairment of vocal fold vibration, maximum phonation time, jitter, shimmer, and harmony-to-noise ratio at the first evaluation. This difference was also found in the glottal gap and maximum phonation time 12 months after the injury., Conclusion: Among patients with thyroid surgery-related unilateral vocal fold paralysis, superior laryngeal nerve injury induces a distinctively different recovery trajectory compared with those without superior laryngeal nerve injury characterized by less reinnervation of vocal fold adductors and worse presentation in terms of the glottal gap and maximum phonation time. This study emphasizes the importance of superior laryngeal nerve function and its preservation in thyroid surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)