tbuckley/cabot-search huggingface dataset:
Modeling Grid Cell Distortions with a Grid Cell Calibration Mechanism
Authors: Daniel Strauß, Zhenshan Bing, Genghang Zhuang, Kai Huang, Alois Knoll
Journal: Cyborg and Bionic Systems (2024)

The medial entorhinal cortex of rodents is known to contain grid cells that exhibit precise periodic firing patterns based on the animal’s position, resulting in a distinct hexagonal pattern in space. These cells have been extensively studied due to their potential to unveil the navigational computations that occur within the mammalian brain and interesting phenomena such as so-called grid cell distortions have been observed. Previous neuronal models of grid cells assumed their firing fields were independent of environmental boundaries. However, more recent research has revealed that the grid pattern is, in fact, dependent on the environment’s boundaries. When rodents are placed in nonsquare cages, the hexagonal pattern tends to become disrupted and adopts different shapes. We believe that these grid cell distortions can provide insights into the underlying neural circuitry involved in grid cell firing. To this end, a calibration circuit for grid cells is proposed. Our simulations demonstrate that this circuit is capable of reproducing grid distortions observed in several previous studies. Our model also reproduces distortions in place cells and incorporates experimentally observed distortions of speed cells, which present further opportunities for exploration. It generates several experimentally testable predictions, including an alternative behavioral description of boundary vector cells that predicts behaviors in nonsquare environments different from the current model of boundary vector cells. In summary, our study proposes a calibration circuit that reproduces observed grid distortions and generates experimentally testable predictions, aiming to provide insights into the neural mechanisms governing spatial computations in mammals.
Development of Wrist Separated Exoskeleton Socket of Myoelectric Prosthsis Hand for Symbrachydactyly
Authors: Yuki Inoue, Yuki Kuroda, Yusuke Yamanoi, Yoshiko Yabuki, Hiroshi Yokoi
Journal: Cyborg and Bionic Systems (2024)

In recent years, the functionality of myoelectric prosthetic hands has improved as motors have become smaller and controls have become more advanced. Attempts have been made to reproduce the rotation and flexion of the wrist by adding degrees of freedom to the wrist joint. However, it is still difficult to fully reproduce the functionality of the wrist joint owing to the weight of the prosthesis and size limitations. In this study, we developed a new socket and prosthetic hand control system that does not interfere with the wrist joint motion. This allows individuals with hand defects who previously used prosthetic hands with fixed wrist joints to freely use their remaining wrist functionality. In the pick-and-place experiment, where blocks were moved from higher to lower locations, we confirmed that the proposed system resulted in a lower elbow position compared with the traditional prosthesis, and the number of blocks transported increased. This significantly reduced the compensatory motion of the elbow and improved the user's performance compared with the use of a conventional prosthetic hand. This study demonstrates the usefulness of a new myoelectric prosthetic hand that utilizes the residual functions of people with hand deficiencies, which have not been utilized in the past, and the direction of its development.
Benefit of perioperative chemotherapy in the patients with loco-regional recurrence of HR-positive HER2-negative breast cancer: A multi-institutional retrospective cohort study.
Authors: Yukinori Ozaki, Emi Tokuda, Fumikata Hara, Shinsuke Sasada, Yasuaki Sagara, Masataka Sawaki, Chizuko Kanbayashi, Takashi Yamanaka, Tatsuya Onishi, Yoshitaka Fujiki, Akihiko Suto, Yuko Takahashi, Eriko Tokunaga, Tomoyuki Aruga, Rikiya Nakamura, Tomomi Fujisawa, Shigehira Saji, Hiroji Iwata, Tadahiko Shien
Journal: Journal of Clinical Oncology (2024)

526 Background: Loco-regional recurrence (LRR) in breast cancer (BC) is addressed with multimodal treatment, yet the prognosis remains unfavorable. The benefit of adjuvant chemotherapy for the hormone receptor-positive, HER2-negative (HR+HER2-) subtype of BC is controversial. Methods: We performed a multi-institutional retrospective cohort study under the Japan Clinical Oncology Group. This study focused on patients without distant metastasis who developed HR+HER2- ipsilateral breast tumor recurrence (IBTR) or other LRR (oLRR) including recurrence in skin, chest wall, or regional lymph nodes. The patients received curative surgery for LRR between 2014 and 2018. Patients were divided into two groups: the chemotherapy group and no chemotherapy group before/after LRR. We performed a Cox proportional hazards model to evaluate invasive disease-free survival (iDFS) between the two groups. Sensitivity analysis was conducted using propensity score (PS) matching and IPTW. Results: A total of 967 patients were registered from 41 institutions, and 958 patients concordant with inclusion criteria were analyzed. There were 509 patients (53%) of only IBTR and 449 patients (47%) of oLRR. Neoadjuvant/Adjuvant chemotherapy was administered to 235 patients (25%), while 722 (75%) did not receive it. Compared to the no-chemotherapy group, the chemotherapy group included a higher number of patients aged 41-60, oLRR, and recurrences during adjuvant endocrine therapy. At a median follow-up of 5.2 years (Interquartile range: 4.1-6.5), the 5-year iDFS rate was 75.4% (95% CI: 72.4-78.2). Multivariate analysis showed an improvement in iDFS for the chemotherapy group (HR: 0.70, 95% CI: 0.49-0.99, p = 0.045). Sensitivity analysis also consistently suggested the effectiveness of chemotherapy (PS matching HR 0.76, IPTW HR 0.75). In the subgroup analysis, the chemotherapy group showed more significant iDFS improvement in cases with oLRR, recurrences during adjuvant endocrine therapy for primary BC, and those without perioperative chemotherapy for primary BC. Conclusions: Our study showed improvement in iDFS in patients who received perioperative chemotherapy for HR+HER2- LRR. This improvement was particularly notable in patients with oLRR, recurrences during adjuvant endocrine therapy, and those without perioperative chemotherapy for primary BC. [Table: see text]
Oncologic outcome of response-guided axillary treatment in patients with cN1 breast cancer after primary systemic therapy.
Authors: Annemiek van Hemert, Ariane van Loevezijn, Marie-Sophie Baas, Marcel P Stokkel, Emilie Groen, Vincent van der Noort, Claudette Loo, Gabe S. Sonke, Nicola Russell, Frederieke H van Duijnhoven, Marie-Jeanne T.F.D Vrancken Peeters
Journal: Journal of Clinical Oncology (2024)

514 Background: In breast cancer, the majority of clinically node positive (cN1) patients are treated with primary systemic treatment (PST), with increasing rates of axillary pathologic complete response (pCR). Evidence supporting tailoring axillary treatment according to the response is growing. However, it is still debatable whether ALND is beneficial in cN1 patients with residual nodal disease and if any further axillary treatment is necessary in patients achieving pCR. In this study, we present the four-year oncologic outcome of cN1 patients undergoing either axillary radiation treatment or no axillary treatment according to the ‘Marking Axillary lymph nodes with Radioactive Iodine seeds’ (MARI)-protocol. Methods: Between 2014 and 2021, we prospectively enrolled patients with node positive breast cancer and 1 - 3 involved axillary lymph nodes on FDG-PET/CT pre-PST, who were treated according to the MARI-protocol. Patients with residual disease of the MARI node (ypN1) received axillary radiotherapy (RT), while patients with a pCR of the MARI node (ypN0) received no further axillary treatment. The primary endpoint was the axillary recurrence rate. Secondary endpoints include invasive disease free survival (iDFS) and overall survival (OS), calculated using the Kaplan-Meier method. Results: Of the 367 included patients, more than half (54%, n= 198) had hormonal receptor positive (HR+)/Human Epidermal growth factor 2 negative (HER2-) breast cancer; 59 patients (16%) had HR+/HER2+; 39 patients (11%) had HR-/HER2+ and 71 patients (19%) had triple negative (TN) subtype. Median age was 49 (IQR 41 – 56) years. 231 (63%) patients who had ypN1 received RT and 136 patients (37%) who achieved ypN0 received no further axillary treatment. Median follow up was 49 (IQR 32 – 70) months. Axillary recurrence rate was 3.5% ( n= 8) in patients with ypN1 and 0.7% ( n= 1) in patients with ypN0. Most axillary recurrences ( n= 6) occurred simultaneously with distant metastases in the ypN1 group. In patients with ypN1, the iDFS was 86% and the OS 93%; in ypN0 patients, the iDFS was 93% and the OS 98%. Conclusions: Response-guided axillary treatment in patients with limited nodal disease according to the MARI protocol is associated with favorable oncologic outcome without performing ALND’s. De-escalation can therefore be considered safe. [Table: see text]
Use of chemotherapy and loco-regional therapy for stage IA triple-negative breast cancer and their association with oncologic outcomes: A cancer registry study.
Authors: André Pfob, Irina Surovtsova, Daria Kokh, Jörg Heil, Maggie Banys-Paluchowski, Philipp Morakis
Journal: Journal of Clinical Oncology (2024)

524 Background: We aimed to evaluate the role of adjuvant chemotherapy and loco-regional therapy for stage IA (pT1, pN0) triple-negative breast cancer (TNBC) in a real-world setting. Methods: We identified patients with pT1, pN0 TNBC diagnosed between 2009 and 2021 within the clinical cancer registry of Baden-Wuerttemberg, Germany. Overall survival (OS) was assessed using Kaplan-Meier statistics and multivariate Cox regression models (adjusted for age, use of chemotherapy, local therapy (breast conserving therapy [breast conserving surgery + radiotherapy] vs. mastectomy), and tumor histologic subtype). Results: A total of 1191 patients with a median follow-up of 43.8 months were identified: 0.9% (11 of 1191) with pT1mi stage, 10.0% (119 of 1191) with pT1a, 24.0% (286 of 1191) with pT1b, and 65.0% (775 of 1191) with pT1c. Use of adjuvant chemotherapy was 9.1% (1 of 11) in pT1mi stage, 41.2% (49 of 119) in pT1a, 66.8% (191 of 286) in pT1b, and 69.8% (541 of 775) in pT1c. Multivariate Cox regression analysis revealed no significant influence for the use of adjuvant chemotherapy on OS in pT1a and pT1b patients (for pT1a HR 1.27, 95% CI 0.19 to 8.50, for pT1b HR 1.07, 95% CI 0.50 to 2.30) but for patient age in the pT1b group (HR 4.71, 95% CI 2.26 to 9.8, for age ≥70 vs. &lt;70 years). For pT1c patients, there was significant influence for the use of adjuvant chemotherapy on OS (HR 0.55, 95% CI 0.38 to 0.8), for local therapy (HR 0.41, 95% 0.25 to 0.69, for breast conserving therapy vs. mastectomy only), and patient age (HR 2.33, 95% CI 1.61 to 3.39 for age ≥70 vs. &lt;70 years). Notably, for pT1c patients aged &lt;70years, local therapy (HR 0.32, 95% CI 0.15-0.69), in favor of breast conserving therapy) but not use of chemotherapy (HR 1.11, 95% CI 0.56-2.19) was associated with OS. Conclusions: This data suggests that OS in stage IA TNBC is strongly influenced by local therapy and patient age, but not use of chemotherapy. Larger studies with longer-term follow-up are welcomed to fully inform this discussion.
Associations between HIV infection status, psychosocial factors, and adjuvant endocrine therapy adherence among South African women with early-stage breast cancer.
Authors: Daniel O'Neil, Charmaine Blanchard, Molly Ream, Keletso Mmoledi, Nontlantla Mkwanazi, Victor Shandukani, Paul Ruff, Michael Antoni, Maureen Joffe
Journal: Journal of Clinical Oncology (2024)

522 Background: South African (SA) women living with comorbid estrogen receptor positive (ER+) breast cancer (BC) and HIV have higher mortality than other SA women with ER+ BC. We aimed to evaluate for associations between HIV status, psychosocial factors, and adjuvant endocrine therapy (AET) adherence as a potential contributor to this disparity. Methods: From Chris Hani Baragwanath Hospital, Johannesburg, we enrolled adult women with stage I-III ER+ BC in remission and currently prescribed tamoxifen or an aromatase inhibitor to a prospective cohort study. We performed AET pill counts at enrollment, 12 weeks, and 24 weeks, and calculated adherence ratios from the difference in pills between visits divided by the number of days between visits. Women completed questionnaires on sources of social support, beliefs about medication, health literacy, and self-efficacy at enrollment and questionnaires about mental health (depression, anxiety, and acute stress) symptom burden and AET-related side effects at the 12- and 24-week visits. We also collected household wealth data and clinical data on BC and HIV. AET adherence ratios were compared between women with and without comorbid HIV using Wilcoxon rank sum testing. We also used structural equation modeling techniques to refine and evaluate an a priori model of AET adherence with latent variables for mental health, socioeconomic (SES) status, healthcare savvy, and AET side effect burden and subgroup analyses of the resulting model in women with and without HIV. Results: Between April 26, 2022, and July 11, 2023, we enrolled 239 women, 63 (26.4%) of whom had co-morbid HIV. Adherence data was available from 106 women at 12 and 24 weeks, from 22 women at 12 weeks only, and from 111 women at 24 weeks only. Comparing women with and without HIV, median AET adherence ratio was 0.88 vs 0.89, respectively (p = 0.65). Our final model of AET adherence achieved good fit (comparative fit index = 0.96, RMSEA 90% CI: 0.03-0.06). In the full cohort, SES quintile showed a trend towards association with AET adherence (β 0.02, SE 0.01, p=0.09); mental health, healthcare savvy, and side effect burden latent variables were not significantly associated with adherence. In the subgroup of women living with HIV, SES quintile (β 0.04, SE 0.02, p=0.08) and mental health (β -0.02, SE 0.01, p=0.10) showed trends toward association with adherence; these relationships did not persist for women without HIV. Conclusions: HIV status is not predictive of AET adherence among SA women with ER+ BC, but in women with both diagnoses, decreasing SES status and increasing mental health symptoms trended towards an association with decreased adherence. Interventions to improve the mental health of SA breast cancer patients living with HIV may promote AET adherence.
Development and validation of RSClin N+ tool for hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer.
Authors: Lajos Pusztai, Jess R Hoag, Kathy S. Albain, William E. Barlow, Salomon M. Stemmer, Allison Meisner, Gabriel N. Hortobagyi, Steven Shak, Daniel F. Hayes, James M. Rae, Frederick Baehner, Priyanka Sharma, Kevin Kalinsky
Journal: Journal of Clinical Oncology (2024)

508 Background: The RSClin tool was developed to provide estimates of recurrence risk and absolute chemotherapy benefit for patients with HR+/HER2- node-negative breast cancer using the 21-gene recurrence score (RS) and clinicopathologic factors. For patients with node-positive disease, we developed a new tool (RSClin N+) to increase the prognostic and predictive utility of risk estimates by combining RS with clinicopathologic factors and menopausal status. Methods: We used Cox regression to estimate 5-year risk of invasive disease or death (iDFS) and likelihood ratio (LR) tests to compare fit of RSClin N+ with RS alone and clinicopathologic factors (tumor grade, tumor size, positive lymph nodes [N1/N2], age) alone in 5283 node-positive patients treated with chemoendocrine therapy (CET) vs endocrine therapy alone (ET) in the S8814 (n=367: N1=227, N2=140, all postmenopausal) and RxPONDER (n/N1=4916) trials. Data from both studies were pooled and stratified by study for postmenopausal models; premenopausal models were fit only on RxPONDER data. Absolute CET benefit across combination of covariate values was estimated as the difference between ET and CET risk estimates. Validation of RSClin N+ was performed in 592 Nmic/N1 patients in the Clalit registry real-world dataset. Results: For pre- and postmenopausal patients, RSClin N+ provided significantly more prognostic information for iDFS than RS or clinicopathologic factors alone (LR Chi-square p&lt;0.05). In postmenopausal patients, RS and clinicopathologic factors were independently prognostic, but only RS showed interaction with CET benefit (p=0.016). Absolute CET benefit for iDFS ranged from &lt;0.1% to 21.5% as the RS increased from 0 to 50. Table shows examples of risk stratification and predicted benefit by RS within clinical low and high risk patients. In premenopausal patients, both RS and clinicopathologic factors remained prognostic but no interaction was observed between RS and CET.In external validation, RSClin N+ risk estimates were concordant with (Lin’s concordance=0.92) and prognostic for observed risk (HR 1.75; 95% CI 1.38 to 2.20). Conclusions: The RSClin N+ model provides improved estimates of prognostic risk and absolute CET benefit than clinical or genomic data alone in node-positive, HR+/HER2- breast cancer and could be used in patient counseling. [Table: see text]
Recurrence score gene axes scores and outcomes by race and ethnicity in the RxPONDER trial.
Authors: Yara Abdou, Jess R Hoag, William E. Barlow, Julie R. Gralow, Funda Meric-Bernstam, Kathy S. Albain, Daniel F. Hayes, Nancy U. Lin, Edith A. Perez, Lori J. Goldstein, Stephen K. L. Chia, Sukhbinder K. Dhesy-Thind, Priya Rastogi, Anne F. Schott, Jennifer M. Racz, Debashish Tripathy, Gabriel N. Hortobagyi, Lajos Pusztai, Priyanka Sharma, Kevin Kalinsky
Journal: Journal of Clinical Oncology (2024)

515 Background: Racial inequities in breast cancer outcomes remain a significant healthcare concern. In a previous analysis of the RxPONDER trial by race/ethnicity, we showed that non-Hispanic Black (NHB) women have worse outcomes compared to non-Hispanic Whites (NHW) despite similar 21-gene recurrence scores (RS). The RS is determined by an assay consisting of 16 cancer-related genes involved in invasion, ER and HER2 signaling, and proliferation. To provide a better understanding of the differences in underlying tumor biology amongst different racial/ethnic groups, we analyzed RS gene axes scores amongst each group and associations with outcomes. Methods: A total of 3,102 women were included: Hispanic (15.5%), NHB (4.7%), Asian (9.5%), and NHW (70.2%). The primary outcome was invasive disease-free survival (IDFS). This analysis extends median follow-up from 5 to 7 years and evaluates gene axes scores that are components of the RS by race/ethnicity. Impact of proliferation, ER, GRB7 (HER2), and invasion axes scores on IDFS was evaluated in Cox regression models. Results: There were no differences in RS distribution across racial/ethnic groups, and RS remained prognostic for each group with no significant variation in RS prognostic value. However, NHBs were noted to have significantly higher proliferation axis scores than NHWs (p&lt;0.001); HER2 axis scores was higher for Asians than NHWs (p&lt;0.001); and Hispanics had both higher HER2 (p=0.002) and proliferation (p=0.02) axes scores compared to NHWs. These results remained statistically significant after adjusting for age. Relative to NHWs, IDFS was worse for NHBs (HR 1.41; 95% CI 0.98-2.03) and better for Asians (HR 0.63; 95% CI 0.43-0.91) in unadjusted analysis. Adjusting for treatment arm, age, grade, menopausal status, proliferation, ER and HER2 axes scores attenuated the impact of race on IDFS for NHBs (HR 1.22; 95% CI 0.84-1.76), although the findings were unchanged for Asians (HR 0.64; 95% CI 0.44-0.93; Table). In a multivariable model, proliferation axis (HR 1.56; 95% CI 1.35-1.80) and ER axis (HR 0.81; 95% CI 0.71-0.93) were prognostic for IDFS. Conclusions: RS gene axes scores differ by race/ethnicity with higher proliferation axis scores noted in NHBs, which could partially explain their inferior outcomes noted in RxPONDER. These findings suggest that tumor biology is indeed important, however, we must dig deeper to uncover intricate factors that contribute to disparities, which is key to designing comprehensive strategies to address them. Clinical trial information: NCT01272037 . [Table: see text]
Clinical relevance of clinical treatment score post 5 years (CTS5) in HR-positive, HER2-positive breast cancer: An exploratory analysis from the HERA trial.
Authors: Soong June Bae, Sohyun Moon, Yoonwon Kook, Seung Ho Baek, Min Ji Lee, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong
Journal: Journal of Clinical Oncology (2024)

519 Background: The clinical treatment score post-5 years (CTS5) has proven valuable in assessing the necessity for extended endocrine therapy among patients with early-stage hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This study aimed to explore the potential of CTS5 as a predictive tool for long-term survival beyond five years in patients with specifically HR-positive, HER2-positive breast cancer. Methods: We collected patient-level data from the HERceptin Adjuvant (HERA) (BIG1-01; NCT00045032) trial. Our investigation focused on assessing the risk of late distant recurrence (DR) and overall survival (OS) according to the CTS5 risk score as continuous value and CTS5 stratification risk groups. Furthermore, we performed a Cox-regression analysis to determine the prognostic performance of CTS5, stratifying subgroups by age and administration of trastuzumab. Results: A total of 1,818 patients with HR-positive, HER2-positive breast cancer were included in this analysis. The CTS5 score, as a continuous variable, emerged as an independent prognostic factor for both late DR (adjusted HR, 2.04; 95% CI, 1.62-2.57; P &lt; 0.001) and OS (adjusted HR, 2.02; 95% CI, 1.58-2.58; P &lt; 0.001), respectively. In addition, multivariable analysis showed a significant association between the high-risk group and adverse outcomes in late DR (adjusted HR, 2.76; 95% CI, 1.84-4.15; P &lt; 0.001) and OS (adjusted HR, 2.45; 95% CI, 1.60-3.74; P &lt; 0.001) compared to low/intermediate group. Consistent results were observed, regardless of age or administration of HER2-targeted therapy. Conclusions: CTS5 is a useful prognostic tool for predicting late DR and OS in HR-positive, HER2-positive breast cancer patients. Extension of endocrine therapy should be actively considered in patients with CTS5 high-risk group.