tbuckley/cabot-search huggingface dataset:
Characteristics of surface electromyography of sternocleidomastoid in infants with congenital muscular torticollis
Authors: Xuan Zhou, Qing Du, Li Zhao, Pinquan Shen, Peijie Chen, Nan Chen, Xiaoyan Yang, Juping Liang
Journal: BMJ (2015)

Objective
To investigate the characteristics of surface electromyography (sEMG) of bilateral sternocleidomastoid in infants with congenital muscular torticollis (CMT).


Methods
Sixty CMT infant patients (CMT group) and 15 healthy infants (control group) were enrolled in this study. The CMT patients were divided into left and right CMT subgroups according to the affected side. The sEMG signals of bilateral sternocleidomastoid during cervical neutral, left and right rotation and lateral flexion posture in the supine position were collected, and the root mean square (RMS) was analyzed.


Results
The RMS value of the affected and unaffected sternocleidomastoid was(8.7±4.4)and (16.3±6.4), respectively in CMT group during cervical neutral in the supine position, and the RMS value of the affected side was significantly lower than that of the unaffected side(t=11.118, P 0.05)in control group during cervical neutral in the supine position. During cervical rotation and lateral flexion, there were no significant differences in the RMS values of bilateral sternocleidomastoid, and the RMS values of bilateral sternocleidomastoid were significantly increased, but there was no significant difference in the increased RMS value of bilateral sternocleidomastoid in control group(P>0.05).


Conclusion
The sEMG characteristics in infants with CMT show that the amount of motor units of the affected sternocleidomastoid which is activated, raised and involved in motions are less, and the muscle excitability is poor. The sEMG characteristics of left and right CMT are consistent.


Key words: 
Electromyography; Infant; Torticollis
Rehabilitation improves the cognition and activity of daily living of patients with vascular dementia
Authors: Ri-guang Hu, Pei-jun Sun, Xian-xiu Liu, Jian-bo Bi, Guang-xia Liang, Li-ying Wang
Journal: BMJ (2006)

Sixty-fourth patients with vascular dementia were recruited in the study and randomly assigned in rehabilitation (medication plus rehabilitation)and control group (medication alone).The treatment period lasted for 12 weeks,the scorings of mini mental statement examination(MMSE) and activity of daily living scale (ADL) were compared before and 4,8,12 weeks after treatment in both group.The scorings of MMSE and ADL in rehabilitation group and control group were both improved after treatment(P ＜0.05),but the scorings in rehabilitation group were better than those in control group(P＜0.05).

Key words: 
Dementia,vascular; Rehabilitation
A CD3 x FRα T-cell engaging bispecific antibody for efficient killing of ovarian cancer cells with minimal cytokine release.
Authors: Ben Buelow, Brian Avanzino, Aarti Balasubramani, Andrew Boudreau, Laura Davison, Priya Ganesan, Katherine Harris, Sharon Hartstein, Harbani Malik-Chaudhry, Duy Pham, Kirthana Prabhakar, Udaya Rangaswamy, Sowmya Saiganesh, Ute Schellenberger, Harshad Ugamraj, Hannes Kehm, Nathan Trinklein, Suhasini Iyer
Journal: Journal of Clinical Oncology (2020)

e18050 Background: Ovarian Cancer (OvCa) is the leading cause of gynecologic cancer mortality in women. Since the introduction of platinum-based chemotherapy there has been little change in the prognosis of OvCa patients, with &lt; 30% overall survival in advanced disease, creating an urgent medical need for novel therapies. Few ovarian epithelium-specific surface proteins are suited for Ab targeting. However, studies have shown folate receptor α (FRα) to be highly over-expressed in OvCa; expression level and stage correlate, and FRα is absent or minimally expressed in normal tissues. However, naked Ab therapy has shown limited efficacy while CAR-T therapy has been plagued by toxicity and limited efficacy. ADCs have demonstrated some activity but present the risk of toxin-mediated side effects. Using Teneobio’s unique antibody discovery platform, we have developed a CD3 x FRα T-BsAb that retains the potent cytotoxicity of other T-cell redirecting therapies but with significantly reduced cytokine release. Methods: Antibodies targeting CD3 and FRα were generated via immunization of our proprietary transgenic animals. Candidate antibodies were selected by repertoire deep sequencing of B-cells from draining lymph nodes, high-throughput gene assembly, recombinant expression, and functional screening. Bispecific antibodies targeting CD3 and FRα were assembled and evaluated for their ability to selectively activate primary human T-cells and mediate killing of FRα+ tumor cells in vitro and in vivo. T-cell activation surface markers, cytokine production and tumor cell cytotoxicity were measured. Results: Primary human T-cells were activated only in the presence of both the CD3 x FRα T-BsAb and FRα (either recombinant or cell-surface protein). Potent and selective cytotoxicity against FRα+ tumor cells was observed in co-cultures of primary human T-cells and OvCa tumor cell lines. Strikingly, our T-BsAb mediated comparable tumor cell cytotoxicity to CD3 x FRα T-BsAbs containing a high affinity anti-CD3 domain but with significantly reduced cytokine production. Our Ab showed preliminary evidence of tumor growth inhibition in xenograft models of OvCa in vivo. Conclusions: We have created a novel CD3 x FRα T-BsAb that mediates T-cell killing of FRα+ tumor cells with minimal production of cytokines. This molecule may improve safety, efficacy, and offer opportunities for combination therapy to treat OvCa.
Distinct genomic and immune microenvironment between thymomas and thymic carcinomas.
Authors: Kaicheng Wang, Suxia Lin, Xue Hou, Yongdong Liu, Meichen Li, Jing Chen, Na Wang, Fang Wang, Jing Bai, Yaping Xu, Likun Chen
Journal: Journal of Clinical Oncology (2020)

e13529 Background: Thymomas and thymic carcinomas which uniformly known as thymic epithelial tumors (TETs) are rare intrathoracic malignancies and a limited studies have been reported addressing the molecular biology and immune discrepancy. The main purpose of this study was to depict the genomic and transcriptomic landscape of thymomas and thymic carcinomas, as well as elucidate the differentiated immune microenvironment. Methods: Totally 15 thymomas and 7 thymic carcinomas patients were enrolled from January 2014 to July 2018. Treatment-naïve tissue samples were collected, and we also obtained matched peripheral blood mononucleocytes as negative control. DNA and RNA were co-extracted and performed with whole exon and transcriptome sequencing. The immune cell infiltration scores were estimated using ssGSEA algorithm. Results: Exome sequencing revealed that GTF2I mutation occurred in all of type A thymomas but was absent in the aggressive subtypes. The median tumor mutation burden of thymomas was 0.12/Mb, significantly lower than thymic carcinomas (median: 1.02/Mb, p = 0.001). Copy number variation was more common in thymic carcinomas than thymomas (83.3% vs 9.1%, p = 0.005). Top mutational signatures enriched in both thymomas and thymic carcinomas included age and Aristolochic acid exposure, while the APOBEC signature was more common in thymomas than thymic carcinomas (81.8% vs 16.7%, p = 0.03). As a confirmed immune escape event, loss of heterozygosity of human leukocyte antigen was identified in 9.1% of thymomas and 50% of thymic carcinomas. Via unsupervised clustering of immune infiltration, all tissue samples were classified into high- and low-infiltration subgroups. Remarkably, up to 71.4% of samples from thymic carcinomas and only 6.7% of samples from thymomas were defined as low immune cell infiltration. In consideration of specific immune cell types, macrophage ( p = 0.01) and neutrophil ( p = 0.02) were enriched in thymic carcinomas while CD56+ NK cell ( p = 0.005) was enriched in thymomas, indicating the evidential discrepancy about immune cell infiltration between two subtypes of TETs. Conclusions: This study elucidated the molecular and immune microenvironment discrepancy between two subtypes of TETs. From molecular perspective, thymomas and thymic carcinomas are entirely different diseases with different etiology and characterized by distinct immune infiltration, and thus should be managed with disparate therapeutic strategies. Findings in this study may also be useful in future targets development and exploration of immunotherapies in TETs.
CFL1 to promote proliferation and invasiveness and to regulate NF-κB-mediated inflammatory factors in hepatocellular carcinoma.
Authors: Chunyan Zhang, Qian Dai, Xiaolu Ma, Wenjing Yang, Lihua Lv, Jie Zhu, Yan Zhou, Baishen Pan, Beili Wang, Xinrong Yang, Wei Guo
Journal: Journal of Clinical Oncology (2020)

e16669 Background: Cofilin1 (CFL1) is an actin-binding protein that plays an essential role in cytoskeleton regulation. However, its function in hepatocellular carcinoma (HCC) is largely unknown. The aim of study was to investigate the role of CFL1 in HCC. Methods: We used qRT-PCR and western blot assays to detect CFL1 expression. The role of CFL1 in regulating HCC cell growth and invasion were assessed by forced expression and downregulation. A tissue microarray study containing 189 HCC cases was conducted to evaluate the clinical relevance and prognostic significance of CFL1. Results: The expression level of CFL1 in high metastasis cell lines was significantly higher than that in low metastasis lines ( P &lt; 0.05). Knockdown of CFL1 reduced the proliferation and invasion activities of Huh7 and MHHC97H cells ( P &lt; 0.05). Western blot revealed that the cytoplasmic level of the p65 subunit of NF-κB was significantly elevated along with reduced nuclear levels and NF-κB-targeted genes MMP9, BCL2, EZH2, COX2 and VCAM1 levels significantly inhibited n HCC cells silenced for CFL1. Immunohistochemistry in a primary tissue array revealed that CFL1 expression correlated with Tumor encapsulation and microvascular invasion ( P &lt; 0.05). High CFL1 expression patients had significantly higher recurrence and deaths rates (recurrence: 72.9% vs. 42.9%, death: 20.8% vs. 51.1%) than low CFL1 expression patients ( P &lt; 0.001). Conclusions: CFL1 regulate the proliferation and dissemination of HCC and TNF-α induced NF-κB nuclear translocation. CFL1 may serve as a prognostic marker in HCC and might be a promising therapeutic target for suppressing metastasis.
Dormancy in Cryptococcus neoformans: 60 years of accumulating evidence
Authors: Alexandre Alanio
Journal: Journal of Clinical Investigation (2020)

Cryptococcus neoformans is an opportunistic yeast that is present worldwide and interacts with various organisms. In humans, it is responsible for cryptococcosis, a deadly invasive fungal infection that represents around 220,000 cases per year worldwide. Starting from the natural history of the disease in humans, there is accumulating evidence on the capacity of this organism to enter dormancy. In response to the harsh host environment, the yeast is able to adapt dramatically and escape the vigilance of the host's immune cells to survive. Indeed, the yeast exposed to the host takes on pleiotropic phenotypes, enabling the generation of populations in heterogeneous states, including dormancy, to eventually survive at low metabolic cost and revive in favorable conditions. The concept of dormancy has been validated in C. neoformans from both epidemiological and genotyping data, and more recently from the biological point of view with the characterization of dormancy through the description of viable but nonculturable cells.
Impact of metabolic syndrome on clinicopathological characteristics and survival of patients with colorectal cancer
Authors: Xin Zhang, Bo Jiang, Likun Zan, Jing Ju, Cunzhi Han, Yan Wang, Lili Du
Journal: BMJ (2019)

Objective
To examine the impact of metabolic syndrome (MS) on the clinicopathological characteristics and prognosis of patients with colorectal cancer (CRC).


Methods
The clinical data of 650 patients with CRC admitted in Shanxi Provincial Cancer Hospital between January 2010 and December 2011 were retrospectively analyzed. Among 650 patients there were 190 cases complicated with MS (MS group) and 460 cases without MS (non-MS group), the clinicopathological features and prognosis were compared between two groups.


Results
The serum insulin and insulin-like growth factor-1 (IGF-1) levels in MS group were significantly higher than those in non-MS group [(9.2±4.7) vs.(6.8±4.7)μIU/L, t=8.88, P<0.01 and (200.2±44.1) vs.(136.7±63.2)mg/L,t=12.63, P<0.01]. The proportions of stage T3 and T4 cancer, extra-regional lymph node metastasis (ELN), and TNM stage Ⅲ and Ⅳ patients in MS group were significantly higher than those in non-MS group [(83.2% (158/190) vs. 72.6% (334/460), χ2=8.19, P=0.04; 9.5% (18/190) vs. 4.8%(22/460),χ2=8.61, P=0.04; 56.3% (107/190) vs. 45.2%(208/460), χ2=8.22, P=0.04, respectively]. The 5-year disease-free survival (DFS) in MS group was significantly lower than that in non-MS group [57.9%(99/171)vs. 66.1%(279/422), P<0.01]. Multivariate analysis indicated that MS(HR=1.623, 95%CI:1.511-1.963, P=0.03), IGF(HR=1.382, 95%CI:1.031-1.765, P=0.02) and, ELN(HR=4.270, 95%CI:2.177-7.463, P<0.01)were independent factors affecting the prognosis of CRC patients.


Conclusion
Metabolic syndrome is one of the risk factors affecting the prognosis of CRC patients.


Key words: 
Colorectal neoplasms; Metabolic syndrome X; Clinicopathological characteristics; Prognosis
Impact of baseline symptom burden as assessed by patient-reported outcomes (PROs) on overall survival (OS) of patients with metastatic cancer.
Authors: Atul Batra, Colleen Ann Cuthbert, Andrew Harper, Lin Yang, Devon J. Boyne, Rodrigo Rigo, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2020)

12020 Background: Patients with metastatic cancer experience variable symptom burden, but serial symptom assessments using PROs may be challenging to implement in routine clinical practices. We aimed to determine if a single measurement of symptom burden at the time of metastatic diagnosis is associated with survival. Methods: We examined prospectively collected baseline PROs of patients newly diagnosed with metastatic breast, lung, colorectal, or prostate cancer using the revised Edmonton Symptom Assessment System (ESASr) questionnaire from a large province (Alberta, Canada) between 2016 and 2019. The ESASr was categorized into physical (PH), psychosocial (PS), and total symptom (TS) domains whereby scores were classified as mild (0-3), moderate (4-6), or severe (7-10). Multivariable Cox proportional hazards models were constructed to evaluate the effect of baseline symptom scores on OS. Results: We identified 1,315 patients, of whom 57% were men and median age was 66 (IQR, 27-93) years. There were 180, 601, 240, and 294 patients with breast, lung, colorectal, and prostate cancer, respectively. Approximately one-quarter of all patients reported moderate to severe PH, PS, and TS scores, with lung cancer patients experiencing the highest symptom intensity across all domains ( P&lt;0.0001). While age did not affect symptom scores, women were more likely to report severe PH, PS, and TS scores as compared to men ( P=0.02, 0.002, and 0.007, respectively). On multivariable Cox regression analysis, older age (HR 1.02, 95% CI, 1.02-1.03, P&lt;0.0001) and female sex (HR 1.67, 95% CI, 1.39-1.99, P&lt;0.0001) were predictive of worse OS as were severe baseline PH and TS scores (see Table) . However, baseline PS scores were not related to OS. Conclusions: A single assessment of baseline symptom burden using the ESASr in patients with metastatic cancer has significant prognostic value. This may represent a feasible first step toward routine collection of PROs in real-world settings where serial symptom measurements can be challenging to implement. [Table: see text]
Clinical analyses of hematological abnormalities in systemic lupus erythematosus
Authors: Wengen Li, Jingye Liao, Chunmei He, Ke Zhang
Journal: BMJ (2014)

To explore the characteristics of hematological abnormalities in patients with systemic lupus erythematosus (SLE) through retrospective analysis. A total of 445 SLE patients were recruited and divided into 5 groups of low white blood cell, immune thrombopenic purpura, anemia, pancytopenia and control without hematological abnormalities. Among them, 351(78.9%) had hematological abnormalities and 94 (21.1%) without hematological abnormities. The prevalence of anemia, leucocytopenia, thrombocytopenia and pancytopenia were 56.0% (246/445), 27.6%(123/445), 13.5%(60/445) and 8.5%(38/445) respectively. The incidence of renal damage in anemia group was significantly higher than that in control group (P<0.01). SLE patients with hematological abnormalities had lower complement C3 levels (P<0.05) and higher systemic lupus erythematosus disease activity index (SLEDAI) (P<0.01). Anemia is the most common findings in SLE patients with hematological abnormalities who have lower complement C3 levels and higher SLEDAI.


Key words: 
Lupus erythematosus, systemic; Hematology
Type, timing, and patient characteristics associated with immune-related adverse event development in patients with advanced solid tumors treated with immune checkpoint inhibitors.
Authors: Qian Qin, Vaibhav G. Patel, Bo Wang, George Mellgard, Mahalya Gogerly-Moragoda, Xiaobo Zhong, Anish B Parikh, Amanda Leiter, Emily J. Gallagher, Matt D. Galsky, William K. Oh, Che-Kai Tsao
Journal: Journal of Clinical Oncology (2020)

e15160 Background: Development (DV) of immune-related adverse events (IRAEs) to immune checkpoint inhibitor (ICI) have been associated (asso/) with (w/) favorable treatment (tx) response, but heterogeneity in clinical presentation remains a concern. We aim to characterize the type, timing, and risk factors asso/ w/ IRAE DV in ICI-treated solid tumor (ST) patients (pts). Methods: The characteristics (char), tx course, and clinical outcomes of ST pts who received at least 2 ICI doses at our institution from 1/1/2011 to 4/29/2017 were reviewed. IRAEs were identified and graded (GR) based on CTCAE (v.4.0). Fisher’s exact test and multivariable regression analyses (MVA) were performed to study the differences between pts w/ versus without (w/o) IRAE. Results: Of the 344 pts identified, 111 pts (32%) had IRAE(s) w/ 145 total events (GR 1: 31%, GR 2: 57%, GR 3: 12%), of which 45% required systemic steroids (SS), 27% lead to ICI discontinuation (DC), and 17% lead to hospitalization (HP, Table). Median time to any IRAE was 12 weeks (w, range 1-149.5w). The most common IRAEs were endocrine (30%), gastrointestinal (GI, 28%), and skin (24%) related. On univariable analysis, antibiotic use, melanoma, and combination ICI use were asso/ w/ IRAE DV; melanoma remained significant on MRA (odds ratio, OR: 3.58 [1.68, 7.64], p = 0.0010). Pts w/ IRAE had higher disease control rate (complete/partial response + stable disease) than pts w/o IRAE (OR: 2.20 [1.29, 3.75], p = 0.0038). Conclusions: Our real-world data showed higher IRAE incidence when compared to those reported in trials, although no GR 4/5 IRAEs occurred. Melanoma was asso/ w/ IRAE DV on MRA, possibly due to the type, dose, and combination of ICIs. These findings warrant further investigation to better identify those at the highest risk to develop clinically significant IRAE. [Table: see text]
Sequential treatment with sorafenib (SOR) followed by regorafenib (REG) in patients (pts) with unresectable hepatocellular carcinoma (HCC): Interim analysis of the observational REFINE study.
Authors: Philippe Merle, Ho Yeong Lim, Richard S. Finn, Masafumi Ikeda, Masatoshi Kudo, Catherine T Frenette, Gianluca Masi, Yoon Jun Kim, René Gerolami, Masayuki Kurosaki, Kazushi Numata, Heinz-Josef Klümpen, Hong Zebger-Gong, Sabine Fiala-Buskies, Kirhan Ozgurdal, Shukui Qin
Journal: Journal of Clinical Oncology (2020)

e16680 Background: REG is approved for the treatment of pts with HCC who previously received SOR, based on results of the phase 3 RESORCE trial. The REFINE study was designed to evaluate the safety and effectiveness of REG in pts with HCC in real-world practice. Methods: This prospective, observational study aims to recruit 1000 pts with unresectable HCC for whom a decision to treat with REG was made by the treating physician prior to enrollment according to the local health authority approved label. The primary endpoint is the incidence of treatment-emergent adverse events (TEAEs) and dose modifications due to TEAEs (NCI-CTCAE v4.03). Secondary endpoints include overall survival (OS) and progression-free survival (investigator assessed). This interim analysis includes the first 500 pts on study for ≥4 months. Results: Of 500 pts enrolled and observed for ≥4 months, 498 received REG and were evaluable (data cut-off: November 11, 2019). Pts were Child-Pugh A 67%, B 11%, C 1%, and missing/not evaluable 21%. Most pts (98%; n = 490) had received prior systemic therapy; 97% (n = 482) had received prior SOR. REG was second line treatment in 81% of pts (n = 403), third line or higher in 17% (n = 87), and first line in 2% (n = 8). Of the 403 pts who received REG second line, 398 (99%) received prior SOR. Among the 482 pts who received SOR in any prior line, the median duration of prior SOR was 4.8 months (interquartile range 2.5–9.6), 45% (n = 216) had a last daily SOR dose of 800 mg, and 8% (n = 40) had a TEAE leading to SOR discontinuation (SOR-intolerant). OS by treatment line is shown in the Table. Among all treated pts, the most frequent TEAEs (any grade) were hand–foot skin reaction (HFSR; 30%), diarrhea (21%), fatigue (16%), and decreased appetite (14%). In SOR-intolerant pts (n = 40), the most frequent TEAEs (any grade) were diarrhea (25%), HFSR (20%), abdominal pain (15%), and decreased appetite (13%). Conclusions: In this interim analysis of REFINE, most pts received REG second line after SOR versus other lines of therapy. Median OS in this subgroup was longer than OS in RESORCE, but the proportion of censored pts was high. The most common TEAEs were similar to those in RESORCE in both the overall cohort and in SOR-intolerant pts. Clinical trial information: NCT03289273 . [Table: see text]