Durable complete remission with local therapies after neoadjuvant and adjuvant nivolumab in recurrent/metastatic head and neck cancer.

Up to 10-15% of patients with first-line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) present with platinum-refractory disease. The anti-PD1 nivolumab is the first therapeutic option in this setting achieving a 19.2% objective response rate and a 7.7-month median overall survival (OS). Given the poor prognosis of platinum-refractory patients, those showing slow progressive disease with no functional status deterioration should maintain nivolumab beyond progression in the absence of severe or unmanageable toxicities. Another strategy is to use local therapies such as radiotherapy and surgical tumor resection in cases of oligometastatic or oligoprogressive disease. Both strategies may significantly improve disease control and OS in these populations. We present the case of a patient with platinum-refractory disease treated with first-line nivolumab beyond progression who achieved a durable complete response after palliative radiation and surgical resection of five tumor lesions. To our knowledge, this is the first reported case of an R/M HNSCC treated with such a strategy outside a clinical trial and contributes to the evidence for combining anti-PD1 agents and local therapies in selected patients with R/M HNSCC.

CAPformer: Pedestrian Crossing Action Prediction Using Transformer.

Anticipating pedestrian crossing behavior in urban scenarios is a challenging task for autonomous vehicles. Early this year, a benchmark comprising JAAD and PIE datasets have been released. In the benchmark, several state-of-the-art methods have been ranked. However, most of the ranked temporal models rely on recurrent architectures. In our case, we propose, as far as we are concerned, the first self-attention alternative, based on transformer architecture, which has had enormous success in natural language processing (NLP) and recently in computer vision. Our architecture is composed of various branches which fuse video and kinematic data. The video branch is based on two possible architectures: RubiksNet and TimeSformer. The kinematic branch is based on different configurations of transformer encoder. Several experiments have been performed mainly focusing on pre-processing input data, highlighting problems with two kinematic data sources: pose keypoints and ego-vehicle speed. Our proposed model results are comparable to PCPA, the best performing model in the benchmark reaching an F1 Score of nearly 0.78 against 0.77. Furthermore, by using only bounding box coordinates and image data, our model surpasses PCPA by a larger margin (F1=0.75 vs. F1=0.72). Our model has proven to be a valid alternative to recurrent architectures, providing advantages such as parallelization and whole sequence processing, learning relationships between samples not possible with recurrent architectures.

Urban Intersection Classification: A Comparative Analysis.

Understanding the scene in front of a vehicle is crucial for self-driving vehicles and Advanced Driver Assistance Systems, and in urban scenarios, intersection areas are one of the most critical, concentrating between 20% to 25% of road fatalities. This research presents a thorough investigation on the detection and classification of urban intersections as seen from onboard front-facing cameras. Different methodologies aimed at classifying intersection geometries have been assessed to provide a comprehensive evaluation of state-of-the-art techniques based on Deep Neural Network (DNN) approaches, including single-frame approaches and temporal integration schemes. A detailed analysis of most popular datasets previously used for the application together with a comparison with ad hoc recorded sequences revealed that the performances strongly depend on the field of view of the camera rather than other characteristics or temporal-integrating techniques. Due to the scarcity of training data, a new dataset is created by performing data augmentation from real-world data through a Generative Adversarial Network (GAN) to increase generalizability as well as to test the influence of data quality. Despite being in the relatively early stages, mainly due to the lack of intersection datasets oriented to the problem, an extensive experimental activity has been performed to analyze the individual performance of each proposed systems.

Hybrid Dynamic Traffic Model for Freeway Flow Analysis Using a Switched Reduced-Order Unknown-Input State Observer.

This paper introduces a new methodology for reconstructing vehicle densities of freeway segments by utilizing the limited data collected by traffic-counting sensors and developing a macroscopic traffic stream model formulated as a switched reduced-order state observer design problem with unknown or partially known inputs. Specifically, the traffic network is modeled as a hybrid dynamic system in a state space that incorporates unknown inputs. For freeway segments with traffic-counting sensors installed, vehicle densities are directly computed using field traffic count data. A reduced-order state observer is designed to analyze traffic state transitions for freeway segments without field traffic count data to indirectly estimate the vehicle densities for each freeway segment. A simulation-based experiment is performed applying the methodology and using data of a segment of Beijing Jingtong freeway in Beijing, China. The model execution results are compared with the field data associated with the same freeway segment, and highly consistent results are achieved. The proposed methodology is expected to be adopted by traffic engineers to evaluate freeway operations and develop effective management strategies.

Trabectedin for reversing platinum resistance and resensitization to platinum in patients with recurrent ovarian cancer.

AIMS: We evaluated trabectedin in patients with platinum-resistant/refractory and partially platinum-sensitive recurrent ovarian cancer and the outcomes after reintroduction of platinum. METHODS: Twenty-seven patients (platinum-resistant/refractory n = 24/PPS; n = 3) treated with trabectedin were retrospectively analyzed. RESULTS: Trabectedin resulted in an objective response rate (ORR) of 18.2% with a 59.1% of disease control rate (ORR plus stable disease). The median progression-free and overall survival were 3.0 and 21.3 months, respectively. Subsequently, 17 patients were retreated with platinum and yield an ORR of 41.2% and DCR of 47.0%. The median progression-free and overall survival after platinum rechallenge were 5.0 and 14.7 months, respectively. CONCLUSION: Our results suggest that trabectedin may contribute to resensitize tumor cells to platinum rechallenge.

A New Switched State Jump Observer for Traffic Density Estimation in Expressways Based on Hybrid-Dynamic-Traffic-Network-Model.

When faced with problems such as traffic state estimation, state prediction, and congestion identification for the expressway network, a novel switched observer design strategy with jump states is required to reconstruct the traffic scene more realistically. In this study, the expressway network is firstly modeled as the special discrete switched system, which is called the piecewise affine system model, a partition of state subspace is introduced, and the convex polytopes are utilized to describe the combination modes of cells. Secondly, based on the hybrid dynamic traffic network model, the corresponding switched observer (including state jumps) is designed. Furthermore, by applying multiple Lyapunov functions and S-procedure theory, the observer design problem can be converted into the existence issue of the solutions to the linear matrix inequality. As a result, a set of gain matrices can be obtained. The estimated states start to jump when the mode changes occur, and the updated value of the estimated state mainly depends on the estimated and the measured values at the previous time. Lastly, the designed state jump observer is applied to the Beijing Jingkai expressway, and the superiority and the feasibility are demonstrated in the application results.

Multicenter analysis of neoadjuvant docetaxel, carboplatin, and trastuzumab in HER2-positive breast cancer.

PURPOSE: In an era where neoadjuvant dual blockade is emerging as the standard of care for early and locally advanced HER2-positive breast cancer, we aimed to identify predictors of response to single-blockade chemotherapy. METHODS: This retrospective analysis reviewed all the incident stage I-III HER2-positive breast cancer patients who received neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) in three institutions. pCR was defined as the absence of invasive tumor in breast and axillary nodes (ypT0/isypN0). RESULTS: From 2008 to 2015, 84 patients receiving neoadjuvant TCH were identified within our institutions. The mean age at diagnosis was 51.8 years. 59.5% of the patients were hormone receptor (HR) positive, lymph node involvement occurred in 67.9%, and clinical distribution was 2.4, 65.5, and 32.1% for stage I, II, and III, respectively. pCR rate was 47.6%; there was a significantly lower response in HR-positive patients compared to HR-negative ones (34 vs 67.6%, p = 0.005). pCR rate was associated with tumor size, whereas differences did not reach significance either for stage or for nodal status. Multivariate analysis found that only HR status was associated with response (p = 0.003). At a median follow-up of 31.7 months, disease-free survival, distant disease-free survival, and overall survival were 78.6, 85.7, and 94%, respectively. Breast-conserving surgery was performed in 44% of the patients. Overall, TCH was well tolerated, with low rates of grade 3-4 adverse events, and neither late toxicities nor cardiac dysfunctions were reported. CONCLUSIONS: Neoadjuvant TCH, an anthracycline-free single-blockade regimen, achieved a pCR of 47.6%. Further molecular analyses are required in order to identify stronger predictive markers of pCR and thus for an accurate selection of patients who do not benefit from dual blockade.

Renal cell cancer metastases to esophagus and stomach successfully treated with radiotherapy and pazopanib.

Renal cell cancer has been rarely reported as a cause of gastric or esophageal metastases. They usually present with gastrointestinal bleeding and most cases have been managed surgically or endoscopically. We report the case of a 38-year-old man with a 4-year history of metastatic renal cell carcinoma admitted to the emergency room with melena and anemia. At endoscopy, three esophageal polypoid lesions (middle and distal thirds) and a 7 cm mass in the gastric fundus were identified. Biopsy revealed esophageal mucosa infiltrated by renal cell carcinoma. Radiotherapy was administered (30 Gy in 10 fractions), followed by pazopanib, with excellent tolerance and without new bleeding episodes. Computed tomography scan showed complete disappearance of the esophageal and fundic lesions at 3 months follow-up. Twenty-four months after being initiated on pazopanib, there is no radiological evidence of disease. This is the first reported case showing complete remission of gastric and esophageal metastases after treatment with radiotherapy and pazopanib.

Predictors of Disease Progression and Adverse Clinical Outcomes in Patients With Moderate Aortic Stenosis Using an Artificial Intelligence-Based Software Platform.

Patients with moderate aortic stenosis (AS) have a greater risk of adverse clinical outcomes than that of the general population. How this risk compares with those with severe AS, along with factors associated with outcomes and disease progression, is less clear. We analyzed serial echoes (from 2017 to 2019) from a single healthcare system using Tempus Next (Chicago, Illinois) software. AS severity was defined according to American Heart Association/American College of Cardiology guidelines. Outcomes of interest included death or heart failure hospitalization. We used Cox proportional hazards models and logistic regression to identify predictors of clinical outcome and disease progression, respectively. From 82,805 echoes for 61,546 patients, 1,770; 914; 565; and 1,463 patients had no, mild, moderate, or severe AS, respectively. Both patients with moderate and those with severe AS experienced a similar prevalence of adverse clinical outcomes (p = 0.45) that was significantly greater than that of patients without AS (p <0.01). In patients with moderate AS, atrial fibrillation (hazard ratio 3.29, 95% confidence interval 1.79 to 6.02, p <0.001) and end-stage renal disease (hazard ratio 3.34, 95% confidence interval 1.87 to 5.95, p <0.001) were associated with adverse clinical outcomes. One-third of patients with moderate AS with a subsequent echo (139/434) progressed to severe AS within 1 year. In conclusion, patients with moderate AS can progress rapidly to severe AS and experience a similar risk of adverse clinical outcomes; predictors include atrial fibrillation and low left ventricular ejection fraction. Machine learning algorithms may help identify these patients. Whether these patients may warrant earlier intervention merits further study.

Advanced penile lymphoma: Case report and review of the literature.

Primary penile lymphomas are extremely rare. They are aggressive neoplasms that can present as double-or triple-hit lymphomas, and because the associate with a high risk of central nervous system dissemination, treatment consists of high-dose chemotherapy regimens plus intrathecal prophylaxis. Pathology can be confused with squamous cell carcinoma of the penis, leading to inappropriate treatments and unnecessary amputations. We report the case of a patient diagnosed with clinical Stage IV penile non-Hodgkin lymphoma that was treated with a complete and durable response. In addition, we review the available literature on penile lymphoma.

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer.

Novel chemo-immunotherapy (chemo-IO) combinations should be evaluated, which may be suitable for cisplatin-unfit or fluoropyrimide-ineligible patients with recurrent or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) to guarantee higher and deeper responses than IO alone. The aim of the present study was to review our experience using pembrolizumab-carboplatin-paclitaxel (pembro + CP) in patients with R/M SCCHN. This was a retrospective study of patients with R/M SCCHN who received pembro + CP in any-line via a compassionate-use program. The present study evaluated safety using Common Terminology Criteria for Adverse Events v4.0, compliance, overall response rate (ORR) and disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors 1.1, duration of treatment, progression-free survival (PFS) and overall survival (OS). Between March 2020 and August 2021, 10 patients were identified (median age, 64 years; female, 60%; Eastern Cooperative Oncology Group 2, 80%). A total of 8 patients received pembro + 3-weekly carboplatin-paclitaxel (3wkCP). A total of 2 patients received pembro + weekly carboplatin-paclitaxel (wkCP). Patients received a median of 3 lines (range, 0-6) of systemic therapy prior to pembro + CP and 80% received IO in previous lines. Grade 1-2 adverse events (AEs) occurred in 100% of patients. Grade 3-5 AEs occurred in 30% of patients [all grade 3 (anemia, neutropenia, thrombopenia, hypertension)]. The mean numbers of pembro + wkCP and pembro + 3wkCP cycles were 2.5 and 6. The ORR (n=7) was 14% (1/7) with one complete response. The DCR was 43% (3/7). The median PFS (n=7) and OS (n=10) times since pembro + CP were 5 months (95% CI, 1-9) and 6 months (95% CI, 0.5-14), respectively. In this small retrospective series of heavily pretreated patients, pembro + CP was well tolerated, and compliance was high. Studies should be conducted to prospectively evaluate the safety and efficacy of this combination in patients with R/M SCCHN.

Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck.

Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min-Max: 31-86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.

A Novel Reconstruction Method for Temperature Distribution Measurement Based on Ultrasonic Tomography.

The precise temperature distribution measurement is crucial in many industrial fields, where ultrasonic tomography (UT) has broad application prospects and significance. In order to improve the resolution of reconstructed temperature distribution images and maintain high accuracy, a novel two-step reconstruction method is proposed in this article. First, the problem of solving the temperature distribution is converted to an optimization problem and then solved by an improved version of the equilibrium optimizer (IEO), in which a new nonlinear time strategy and novel population update rules are deployed. Then, based on the low-resolution and high-precision images reconstructed by IEO, Gaussian process regression (GPR) is adopted to enhance image resolution and keep the reconstruction errors low. After that, the number of divided grids and the parameters of IEO are also further studied to improve the reconstruction quality. The results of numerical simulations and experiments indicate that high-resolution images with low reconstruction errors can be reconstructed effectively by the proposed IEO-GPR method, and it also shows excellent robust performance. For a complex three-peak temperature distribution, a competitive accuracy with 3.10% and 2.37% error at root-mean-square error and average relative error is achieved, respectively. In practical experiment, the root-mean-square error of IEO-GPR is 0.72%, which is at least 0.89% lower than that of conventional algorithms.

Enhanced Detection of Heart Valve Disease Using Integrated Artificial Intelligence at Scale.

BACKGROUND: Undertreatment of heart valve disease creates unnecessary patient risk. Poorly integrated healthcare data systems are unequipped to solve this problem. A software program using a rules-based algorithm to search the electronic health record for heart valve disease among patients treated by healthcare systems in the United States may provide a solution. METHODS: A software interface allowed concurrent access to picture archiving communication systems, the electronic health record, and other sources. The software platform was created to programmatically run a rules engine to search structured and unstructured data for identification of moderate or severe heart valve disease using guideline-reported values. Incidence and progression of disease as well as compliance with a care pathway were assessed. RESULTS: In 2 health institutions in the United States 60,145 patients had 77,215 echocardiograms. Moderate or severe aortic stenosis (AS) was identified at a rate of 9.1% of patients (5474 and 6910 echocardiograms) in this population. The precision and accuracy of the algorithm for the detection of moderate or severe AS was 92.9% and 98.6%, respectively. Thirty-five percent of patients (441/1265) with moderate stenosis and a subsequent echocardiogram progressed to severe stenosis (mean interval, 358 days). In 1 sample 70.3% of moderate AS patients lacked a 6-month echocardiogram or appointment. The platform enabled 100% accountability for all patients with severe AS. CONCLUSIONS: A rules-based software program enhances detection of heart valve disease and can be used to measures disease progression and care pathway compliance.

Clinical Predictors of Mortality in Patients with Moderate to Severe Mitral Regurgitation.

BACKGROUND: Mitral regurgitation is the most common form of valvular heart disease worldwide, however, there is an incomplete understanding of predictors of mortality in this population. This study sought to identify risk factors of mortality in a real-world population with mitral regurgitation. METHODS: All patients with moderate or severe mitral regurgitation were identified at a single center from January 1, 2016 to August 31, 2017. Multivariate regression was performed to evaluate variables independently associated with all-cause mortality. RESULTS: A total of 490 patients with moderate (76.3%) or severe (23.7%) mitral regurgitation due to primary (20.8%) or secondary (79.2%) etiology were identified. The mean age was 66.7 years; 50% were male. At a median follow-up of 3.1 years, the incidence of all-cause mortality was 30.1%, heart failure hospitalization 23.1%, and mitral valve intervention 11.6%. Of 117 variables, multivariate analysis demonstrated 5 that were independently predictive of mortality: baseline creatinine (hazard ratio [HR] 1.2; 95% CI, 1.0-1.3; P = .02), right atrial pressure by echocardiogram (HR 1.3; 95% CI, 1.07-1.55; P = .008), hemoglobin (HR 0.65; 95% CI, 0.52-0.83; P = .001), hospitalization for heart failure (HR 1.6; 95% CI, 1.1-2.4; P = .015), and mitral valve intervention (HR 0.40; 95% CI, 0.16-0.83; P = .049). CONCLUSION: In this retrospective, pragmatic analysis of patients with moderate or severe mitral regurgitation, admission for heart failure exacerbation, elevated right atrial pressure, renal dysfunction, anemia, and lack of mitral valve intervention were independently associated with increased risk of all-cause mortality. Whether these risk factors may better identify select patients who may benefit from more intensive monitoring or earlier intervention should be considered in future studies.

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study.

BACKGROUND: Axitinib monotherapy obtained approval in pre-treated mRCC patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified. PATIENTS AND METHODS: Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months vs. disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed. RESULTS: In total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 vs. 26.5 months; P = .009). In LR vs. RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 vs. 10.9 months P < .001). The safety profile was manageable and consistent with known data. CONCLUSIONS: This study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib.

Application of suppressive subtractive hybridization to the identification of genetic differences between two Lactococcus garvieae strains showing distinct differences in virulence for rainbow trout and mouse.

Lactococcus garvieae is the causative microbial agent of lactococcosis, an important and damaging fish disease in aquaculture. This bacterium has also been isolated from vegetables, milk, cheese, meat and sausages, from cow and buffalo as a mastitis agent, and even from humans, as an opportunistic infectious agent. In this work pathogenicity experiments were performed in rainbow trout and mouse models with strains isolated from human (L. garvieae HF) and rainbow trout (L. garvieae UNIUDO74; henceforth referred to as 074). The mean LD(50) value in rainbow trout obtained for strain 074 was 2.1 × 10(2) ± 84 per fish. High doses of the bacteria caused specific signs of disease as well as histological alterations in mice. In contrast, strain HF did not prove to be pathogenic either for rainbow trout or for mice. Based on these virulence differences, two suppressive subtractive hybridizations were carried out to identify unique genetic sequences present in L. garvieae HF (SSHI) and L. garvieae 074 (SSHII). Differential dot-blot screening of the subtracted libraries allowed the identification of 26 and 13 putative ORFs specific for L. garvieae HF and L. garvieae 074, respectively. Additionally, a PCR-based screening of 12 of the 26 HF-specific putative ORFs and the 13 074-specific ones was conducted to identify their presence/absence in 25 L. garvieae strains isolated from different origins and geographical areas. This study demonstrates the existence of genetic heterogeneity within L. garvieae isolates and provides a more complete picture of the genetic background of this bacterium.

Adaptive road crack detection system by pavement classification.

This paper presents a road distress detection system involving the phases needed to properly deal with fully automatic road distress assessment. A vehicle equipped with line scan cameras, laser illumination and acquisition HW-SW is used to storage the digital images that will be further processed to identify road cracks. Pre-processing is firstly carried out to both smooth the texture and enhance the linear features. Non-crack features detection is then applied to mask areas of the images with joints, sealed cracks and white painting, that usually generate false positive cracking. A seed-based approach is proposed to deal with road crack detection, combining Multiple Directional Non-Minimum Suppression (MDNMS) with a symmetry check. Seeds are linked by computing the paths with the lowest cost that meet the symmetry restrictions. The whole detection process involves the use of several parameters. A correct setting becomes essential to get optimal results without manual intervention. A fully automatic approach by means of a linear SVM-based classifier ensemble able to distinguish between up to 10 different types of pavement that appear in the Spanish roads is proposed. The optimal feature vector includes different texture-based features. The parameters are then tuned depending on the output provided by the classifier. Regarding non-crack features detection, results show that the introduction of such module reduces the impact of false positives due to non-crack features up to a factor of 2. In addition, the observed performance of the crack detection system is significantly boosted by adapting the parameters to the type of pavement.

Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity.

Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome. Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity. Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6). Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection. Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.