tbuckley/cabot-search huggingface dataset:
Obesity as a prognostic factor for incidence and survival in female patients diagnosed with breast cancer.
Authors: Islam Elsayed Ramadan
Journal: Journal of Clinical Oncology (2013)

e12567 Background: The incidence of obesity in females ≥15 years of age in Egypt is one of the highest all over the world (33%)we investigated the impact of increased BMI on breast cancer incidence and survival. Methods: we reviewed files for 1873 female patients with breast cancer, presented at ACOD, from Jan. 1996 to Dec. 2005. , only 907 were eligible BMI of every patient was calculated and four groups were formed.The duration of follow-up was calculated from the date of registration to the date of death or last follow-up. The locoregional control period was between the end of treatment and failure of local control at 5 years or death or last follow-up OS was measured as the interval between the beginning of treatment and death or last follow-up evaluation. Results: patients were classified into 4 groups, the first group included 100 patients of BMI less than 18.5, the second group including 299 patients of BMI more than or equal to 18.5 and less than 25, the third group including 336 patients of BMI more than or equal to 25 and less than 30, and the fourth group including 172 patients of BMI more than 30. the highest peak of breast cancer incidence was in the age group 55-65 years (32.4%), while the lowest incidence was in the age group more than 65 (8.6%). Obese patients had the tendency to have breast cancer in younger age than normal weight patients with a mean of 38.6 years vs. 58.6 years. results showed that over weight patients constituted more than 37% while obese patients only constituted 19 %, normal weight 33% and underweight 11%. In our study, the majority of cases were staged as stage II and III (42.6 and 45.9 % respectively). Only 10.2% of patients in our series were recorded with stage IV; most of them were obese.Patients with increased BMI, in our study, had a significantly lower DFS ( p &lt; 0.013).there was a statistically significant correlation between overall survival and BMI of patients (p=0.0015); there was an increase in mortality with increasing BMI. Conclusions: Our results report an increase in the incidence of breast cancer in overweight and obese patients in our population. Patients with high BMI were diagnosed at younger age, had more advanced stage and a statistically significant lower DFS &amp; OS as compared to normal weight patients.
Capturing sleep–wake cycles by using day-to-day smartphone touchscreen interactions
Authors: Jay N. Borger, Reto Huber, Arko Ghosh
Journal: npj Digital Medicine (2019)

Body movements drop with sleep, and this behavioural signature is widely exploited to infer sleep duration. However, a reduction in body movements may also occur in periods of intense cognitive activity, and the ubiquitous use of smartphones may capture these wakeful periods otherwise hidden in the standard measures of sleep. Here, we continuously captured the gross body movements using standard wrist-worn accelerometers to quantify sleep (actigraphy) and logged the timing of the day-to-day touchscreen events ('tappigraphy'). Using these measures, we addressed how the gross body movements overlap with the cognitively engaging digital behaviour (from n = 79 individuals, accumulating ~1400 nights). We find that smartphone use was distributed across a broad spectrum of physical activity levels, but consistently peaked at rest. We estimated the putative sleep onset and wake-up times from the actigraphy data to find that these times were well correlated to the estimates from tappigraphy (R2 = 0.9 for sleep-onset time and wake-up time). However, actigraphy overestimated sleep as virtually all of the users used their phones during the putative sleep period. Interestingly, the probability of touches remained greater than zero for ~2 h after the putative sleep onset, and ~2 h before the putative wake-up time. Our findings suggest that touchscreen interactions are widely integrated into modern sleeping habits-surrounding both sleep onset and waking-up periods-yielding a new approach to measuring sleep. Smartphone interactions can be leveraged to update the behavioural signatures of sleep with these peculiarities of modern digital behaviour.
Developing a predictive model for disease status in breast cancer patients using Th1 and Th2 serum cytokine profiles
Authors: S. Khoo, T. Kao, Z. A. Dehqanzada, C. E. Storrer, K. A. Harris, Y. H. Jama, C. D. Shriver, S. Ponniah, G. E. Peoples
Journal: Journal of Clinical Oncology (2006)

10078 Background: Using the Luminex multiplex assay, we have reported significant correlations between serum levels of MCP-1, eotaxin, and IL-6 and disease characteristics in breast cancer (BCa) patients. We now examine the potential of utilizing a general cytokine profile to develop a statistical model to predict certain disease states in these patients. Methods: Sera from 36 BCa patients (24 node-negative, 12 node-positive, 12 normals) were analyzed using the Luminex assay for levels of 21 cytokines (IL-1α, 1b, 2, 4, 5, 6, 8, 10, 12, 13, 15, 17, IFN-γ, G-CSF, GM-CSF, TNF-α, IP-10, MIP-1α, RANTES, MCP-1, eotaxin). Logistic regression models were used to assess if a binary outcome variable (Y) can be predicted by using serum cytokine levels (X). The area under a receiver operating characteristic (ROC) curve (c) was used to assess the potential utility of a biomarker. The larger the value of c, the better the biomarker. Results: MCP-1 was found to be a possible predictor of the presence of BCa while other potential biomarkers were IL-13, MIP-1α and eotaxin. The higher the MCP-1 level, the greater the likelihood that the patient would have BCa. Similar relationships applied to the other potential biomarkers. Among BCa patients, GM-CSF seemed to be a good predictor of nodal status with lower levels of GM-CSF predicting positive nodes. Other potential biomarkers with a similar expression pattern for nodal status were MCP-1, IL-6 and IL-5. Due to small sample sizes, we were unable to examine a potential “panel” of cytokines to develop a prognostic algorithm based on serum analysis. Conclusions: MCP-1, which was previously shown to be elevated in BCa, may also have some predictive value linking the presence of disease and disease severity as measured by nodal status. Other prominent cytokines from earlier studies (MIP-1α, eotaxin, IL-6) also displayed some possible predictive value. Our results warrant studying a larger population in order to establish a unified prognostic formula for BCa based on serum cytokine levels. [Table: see text] No significant financial relationships to disclose.
Cetuximab, fluorouracil (5-FU), cisplatin, and docetaxel as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Interim results of a randomized phase II clinical trial (CeFCiD).
Authors: Maren Knoedler, Andreas Dietz, Thomas Christoph Gauler, Viktor Gruenwald, Jan Stoehlmacher, Stephan Knipping, Orlando Guntinas-Lichius, Norbert Frickhofen, Michael Schroeder, Georg Maschmeyer, Volker Rethwisch, Boris Haxel, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2013)

e17021 Background: This study investigates efficacy and toxicity of docetaxel added to cetuximab, cisplatin and 5-FU for patients with R/M SCCHN. We here report a planned second interim analysis to compare response rates between arms in order to decide on continuing to full accrual. Methods: Inclusion criteria were: stage III/IV R/M SCCHN and ECOG 0-1. Patients were randomized to arm A: cetuximab (standard dose) plus a maximum of 6 cycles of docetaxel (40 mg/m², day 1+8), cisplatin (40 mg/m², day 1+8) and 5-FU (2000 mg/m², day 1+8) or to arm B: cetuximab (standard dose), cisplatin (100 mg/m², day 1) and 5-FU (1000 mg/m², day 1-4). Treatment was administered until progression or intolerability. The endpoint of this analysis was RR. Results: A first interim analysis for toxicity after treatment of 20 patients per arm revealed more hematologic and gastrointestinal grade III/IV toxicities in the experimental arm. Therefore dose reductions of cisplatin from 40 to 30 mg/m² and 5-FU from 2,000 to 1,000 mg/m² had been introduced. A secondary toxicity analysis with 40 patients per arm observed reduced treatment related toxicities. Currently 100 patients could be assessed for response: arm A: 82 % male, median age 58 years, arm B: 82 % male, median age 60 years. Best overall RR was 41 % (3 CR, 18 PR) in arm A compared to 45 % (4 CR, 19 PR) in arm B. The DCR was 75 % in arm A and 80 % in arm B. Conclusions: After introducing dose reductions toxicity is manageable. Comparable response rates were seen in both arms. CeFCiD continues per protocol for evaluation of the primary endpoint PFS. Enrollment is estimated to be completed in Aug 2013. Clinical trial information: CeFCiD-1108.
Use of the SFMA as a measure of overall functionality in patients undergoing hematopoietic stem cell transplantation (HSCT).
Authors: Charlotte Shatten, William Allen Wood, Robert Butler, Claudio Battaglini
Journal: Journal of Clinical Oncology (2013)

7119 Background: The 6 minute walk test (6MW) has been used in research as a measure of overall functionality and has been related to prognosis and quality of life (QOL) in cancer patients. For some clinics, the use of other functional tests may be a timely and space saving option. The selective functional movement assessment (SFMA) is a short, systematic evaluation of 7 fundamental movement patterns which can be conducted in patient rooms. The SFMA can make clinicians aware of deficient, painful movement patterns that may indicate impairment and motor control deficits. The SFMA may help identify functional impairments for pre- and peri-transplant interventions in patients undergoing HSCT. Methods: Patients were assessed prior to HSCT. A composite score (range: 19-38) was given to patients based SFMA performance. A lower score represented improved movement profiles. 6MW was tested by standardized protocol on an established route. Pearson correlations were calculated to evaluate the relationship between 6MW and SFMA. Results: We evaluated 32 patients (10 autologous, 11 myeloablative allogeneic, 11 reduced intensity allogeneic). One patient was unable to complete all portions of the SFMA due to physical limitations; all patients completed the 6MW. The mean SFMA composite score was 24.9± 3. ≥50% of patients exhibited deficient movement patterns during forward flexion and deep squat. Other patterns that showed a high level of deficiency (&gt; 30% of all patients) were back extension, single leg stance, shoulder mobility, and cervical rotation. The mean 6MW was 477± 94 m. There was a moderate negative correlation between 6MW and SFMA composite score (r =-0.46, p&lt;0.001), implying that a shorter 6MW was associated with more deficient movements. Conclusions: The SFMA could be useful for quantifying overall functionality in settings where the 6MW is not ideal. The SFMA may also be useful for identification of functional issues that may be addressed before or during HSCT by interventions to limit disability and maintain QOL. Further research should evaluate the SFMA results pre to post transplant to assess changes in fundamental movement deficits. The use of the SFMA’s prognostic ability should also be evaluated.
Dewan Wahedun Nabi
Authors: Shahrina Nabi Mianoor
Journal: BMJ (2019)

Dewan Wahedun Nabi (“Waheed”) completed his MBBS qualifications in Rajshahi Medical College, Bangladesh in 1967. He came to the UK in the 1970s to achieve further postgraduate qualifications.

He used to say that his first ambition had been to be a professional football player, but his father encouraged him to switch to cricket, as this was considered a “gentleman’s sport”; unfortunately he broke his arm and concentrated on his studies.

Waheed did his training in Yorkshire and the West Midlands. He gained membership of the Royal College of Psychiatrists in 1983 and the Diploma in Psychological Medicine soon after. He was appointed consultant psychiatrist for old age at Rotherham District General Hospital in 1992. He was extremely proud to be awarded fellowship of the RCPsych in 2004. He retired in 2008 but …
Association of Psychiatric Comorbidity With the Risk of Premature Death Among Children and Adults With Attention-Deficit/Hyperactivity Disorder
Authors: Shihua Sun, Ralf Kuja-Halkola, Stephen V. Faraone, Brian M. D’Onofrio, Søren Dalsgaard, Zheng Chang, Henrik Larsson
Journal: JAMA Psychiatry (2019)

A previous register-based study reported elevated all-cause mortality in attention-deficit/hyperactivity disorder (ADHD), but cause-specific risks and the potential associations of psychiatric comorbidities remain unknown.
Therapeutic target expression in advanced prostate cancer patients submitted for comprehensive molecular profiling.
Authors: Brian Wright, Matthew Jerome McGinniss, Anatole Ghazalpour, Christopher Roberts, Ryan P Bender, Rebecca A Feldman, Lori Brisbin, Gargi D. Basu
Journal: Journal of Clinical Oncology (2012)

e15209 Background: Approximately 30,000 men die from advanced PCa annually. The prognosis of this disease stresses a need for novel therapeutic and clinical strategies. Methods: We analyzed targeted genes and proteins in 141 patient specimens using IHC (for as many as 29 different biomarkers), FISH for EGFR, ALK, c-Myc, Her2neu and TOP2A, sequencing for BRAF, c-ckit, EGFR, KRAS, and PIK3CA, and RNA expression microarray. Therapeutic associations from the published literature were then assigned based on the differentially expressed biomarkers. Due to amount of tumor tissue present in the specimen, physician test requests and other factors, the number of biomarkers interrogated varied from case to case. Results: Therapeutic associations based on IHC results included:) 92% HER2 negative (potential lack of benefit from HER2 targeted therapy); 85% AR high (potential benefit from anti-androgen therapy); 79% ERCC1 negative (potential benefit from platinum-based therapies); 70% TS negative (potential benefit from fluorouracil),54% PTEN negative (suggesting activation of PIK3CA pathway), 66% RRM1 low (potential benefit from gemcitabine); 64% TOPO2A low (potential lack of benefit from anthracyclines); 44% TOPO1 high (potential benefit from irinotecan) 34% MGMT high (potential lack of benefit from temozolomide); 28% SPARC high (potential benefit from nab-paclitaxel). Potential therapeutic associations based on FISH and Sequencing included: 82% HER2 negative by FISH (potential minimal benefit to HER2 targeted therapy), 13% EGFR positive by FISH and a majority 90% and 81% wild-type for KRAS (exons 2, 3) and BRAF (exons 11, 15), respectively, indicating potential benefit from EGFR targeted therapies. Interestingly, two drug pumps, PGP and MRP1 were 85% negative and 91% positive, respectively. Conclusions: Advanced PCa is an aggressive disease where a one-size-fit-all approach is not effective. Our data confirms that these tumors are heterogeneous at the molecular level and has important therapeutic implications. When developing biomarker enriched clinical trials or advanced treatment planning, a comprehensive molecular profile may provide important insights not otherwise considered.
Outcome of risk-adapted therapy for pediatric acute lymphoblastic leukemia in Egypt.
Authors: Iman A. Sidhom, Abir Mokhles, Sonya Soliman, Khaled Shaaban, Sherine Salem, Dina Yassin, Hala Hassanein, Nayera Hamdy, Waffa Rashed, Amr El-Nashar, Hadeel Magdi, Alaa Elhaddad
Journal: Journal of Clinical Oncology (2013)

10044 Background: With modern risk directed therapy, &gt;80% of children with acute lymphoblastic leukemia (ALL) in western countries are cured. The 5-year event free survival (EFS) and relapse free survival (RFS) of pediatric ALL patients in Egypt were 65% and 75% respectively in a previous study using an intensive treatment protocol for all patients. Aim: To improve cure rates of Egyptian children with ALL using risk adapted therapy. Methods: From July 2007 to December 2010, 706 patients aged 1-18 years with newly diagnosed ALL were treated at Children Cancer Hospital Egypt with a risk directed ALL protocol adopted from St Jude Total Study XV. Results: B-precursor phenotype was encountered in 75.8% and T-cell in 24.2%. Based on initial presentation and response to therapy measured by minimal residual disease (MRD), 42.6%, 45.8% and 11.6% of the patients were classified as low, intermediate and high risk respectively. The 5-year RFS and EFS were 88.2 ± 1.5% and 76.5 ± 1.7% respectively. Adverse events included 4.4% induction deaths, 2.5% failure to achieve induction remission (1.4% remained refractory), 6.8% deaths in remission, 9.2% relapses (3.1% hematological, 1.8% combined hematological and CNS, 4% isolated CNS, 0.3% isolated testicular), 0.9% abandonment of therapy and one patient had secondary myeloid leukemia. The median follow up for patients alive in CR was 43months (range 24–65). The 5-year RFS of the low, intermediate and high risk groups were 92.2 ± 2.4%, 85.3 ± 2.2% and 82.7 ± 4.8% respectively (p=0.001), while the 5-year EFS were 87.6 ± 2.5%, 78.2 ± 2.5% and 57.9 ± 5.7% respectively (p&lt;0.001). Prognostic factors that had statistically significant unfavorable impact on both EFS and RFS by univariate analysis were age ≥10 years, TLC ≥100x10 9 /L, T-cell phenotype, risk groups, MRD d42 ≥1% and MRD W7 ≥0.1%, while MRD d15 ≥1% had statistically significant unfavorable outcome on EFS only. By multivariate analysis, TLC and MRD W7 had prognostic significance on EFS and RFS, MRD d42 on EFS, while MRD d15 had marginal significance on EFS (p=0.055). Conclusions: Risk adapted therapy was effective in improving ALL survival among patients at our institution compared with previous trials, although the outcome remains lower than that in high income countries.
Functional association of a CD40 gene single-nucleotide polymorphism with the pathogenesis of coronary heart disease
Authors: Cheryl S Sultan, Michael Weitnauer, Martin Turinsky, Thorsten Kessler, Maik Brune, Christian A Gleissner, Florian Leuschner, Andreas H Wagner, Markus Hecker
Journal: Cardiovascular Research (2019)

Abstract Aims Endothelial dysfunction is a major contributor to the pathogenesis of atherosclerosis. CD40–CD40 ligand interactions confer a pro-inflammatory phenotype to endothelial cells (ECs). Recently, a thymine to cytosine transition (−1T&amp;gt;C) in the Kozak sequence of the CD40 gene (rs1883832) has been associated with coronary heart disease (CHD) in an Asian population. As there are no reports yet regarding its role in other ethnic groups, this study determines if the −1T&amp;gt;C single-nucleotide polymorphism (SNP) could be a risk factor for CHD in Caucasians by performing an association study and elucidates its functional consequence in cultured ECs. Methods and results Molecular and biochemical techniques, cell adhesion assays were used for genotype-stratified human EC characterization. SNP distribution in Caucasians was examined in a hospital-based case–control CHD study and serum levels of soluble CD40 (sCD40) were quantified by ELISA. The SNP in the CD40 gene affected baseline CD40 protein abundance on ECs. There was a genotype-dependent difference in CD40-mediated expression of pro-inflammatory genes. Monocyte adhesion was highest on the surface of cells homozygous for the C allele. Homozygosity for the C allele was associated with significant 2.32-fold higher odds of developing CHD as compared to TT genotype carriers. sCD40 plasma levels were genotype-dependently elevated in CHD patients, indicating a possible prognostic value. Conclusion The C allele of the CD40 SNP provokes a pro-inflammatory EC phenotype, compensated by an enhanced CD40 shedding to neutralize excess CD40 ligand. Homozygosity for the C allele is the cause for a genetic susceptibility to atherosclerosis and its sequelae.
Prognostic role of somatostatin receptor subtypes in human prostate cancer
Authors: A. Gernone, V. Pagliarulo, S. Trabucco
Journal: Journal of Clinical Oncology (2009)

e16120 Background: Neuroendocrine differentiation (NED) in prostate carcinoma (PC) is frequently detected by immunohistochemistry as single cells in conventional adenocarcinoma. NED of PC correlates with poor prognosis and tumor progression during androgen-deprivation therapy. The aim of our study was to correlate the expression of somatostatin receptor (SSTR) 1, 2, 3, 4, 5 subtypes in primary PC with NED pattern and Overall Survival (OS). Methods. PC tissues were reviewed from 100 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2002 to 2007. 24 samples expressed hystologically chromogranin A (CgA), a marker of NED expression. Patient characteristics included: median age 68 years (range 45–83), median baseline PSA: 70 ng/ml (range 0.3–200), median ECOG Performance Status: 1 (range 0–2), Gleason score ≥ 7, medium serum level of CgA was 56.2 nmol/L (range 0.5–120). Results: The expression of SSTR subtypes (1, 2, 3, 4, 5) were investigated and our data identified four histological features. SSTR1 was expressed in 4/24 samples, SSTR 5 was detected in 2/24 samples, both SSTR1 and SSTR5 were found in 6/24 samples. OS at last follow up on July 2008 was 60%. SSTR 1–5 were undetectable in 12/24 pts with more aggressive clinical course and the OS was &lt; 10%. The PSA and CgA levels were not correlated with clinical outcome. SSTR subtypes 2, 3 an 4 were not expressed in all 24 samples. Conclusions: SSTRs expression significantly correlated with OS. The absence of SSTR 1 and 5 in more aggressive disease could represent a growth advantage in NED prostate cancer. SSTRs and somatostatin analogs are potential targets for prostate cancer treatment. No significant financial relationships to disclose.
Polyclonal Heterogeneity: The New Norm for Secondary Clinical Resistance to Targeted Monotherapy in Relapsed Leukemia?
Authors: Andrew H. Wei, Andrew W. Roberts
Journal: Cancer Discovery (2019)

Abstract Summary: In this issue, McMahon and colleagues demonstrate that secondary clinical resistance to the FLT3 inhibitor gilteritinib in relapsed acute myeloid leukemia is often polyclonal and commonly mediated by heterogeneous mutations that activate downstream RAS–MAPK pathways. These findings and recent data from others indicate that emergence of multiple clones, each with distinct mechanisms of resistance, is a common finding at secondary failure of single-agent–targeted therapies for relapsed leukemias. See related article by McMahon et al., p. 1050.
Multifunctional magnetic hairbot for untethered osteogenesis, ultrasound contrast imaging and drug delivery
Authors: Ajay Vikram Singh, Mohammad Hasan Dad Ansari, Cem Balda Dayan, Joshua Giltinan, Shuo Wang, Yan Yu, Vimal Kishore, Peter Laux, Andreas Luch, Metin Sitti
Journal: Biomaterials (2019)
Targeted Cortical Manipulation of Auditory Perception
Authors: Sebastian Ceballo, Zuzanna Piwkowska, Jacques Bourg, Aurélie Daret, Brice Bathellier
Journal: Neuron (2019)

Driving perception by direct activation of neural ensembles in cortex is a necessary step for achieving a causal understanding of the neural code for auditory perception and developing central sensory rehabilitation methods. Here, using optogenetic manipulations during an auditory discrimination task in mice, we show that auditory cortex can be short-circuited by coarser pathways for simple sound identification. Yet when the sensory decision becomes more complex, involving temporal integration of information, auditory cortex activity is required for sound discrimination and targeted activation of specific cortical ensembles changes perceptual decisions, as predicted by our readout of the cortical code. Hence, auditory cortex representations contribute to sound discriminations by refining decisions from parallel routes.