tbuckley/cabot-search huggingface dataset:
Large-scale transcriptomic analysis reveals that pridopidine reverses aberrant gene expression and activates neuroprotective pathways in the YAC128 HD mouse
Authors: Rebecca Kusko, Jennifer Dreymann, Jermaine Ross, Yoonjeong Cha, Renan Escalante-Chong, Marta Garcia-Miralles, Liang Juin Tan, Michael E. Burczynski, Ben Zeskind, Daphna Laifenfeld, Mahmoud Pouladi, Michal Geva, Iris Grossman, Michael R. Hayden
Journal: Molecular Neurodegeneration (2018)

Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of transcriptional pathways. Pridopidine, a small molecule in development for treatment of HD, has been shown to improve motor symptoms in HD patients. In HD animal models, pridopidine exerts neuroprotective effects and improves behavioral and motor functions. Pridopidine binds primarily to the sigma-1 receptor, (IC50 ~ 100 nM), which mediates its neuroprotective properties, such as rescue of spine density and aberrant calcium signaling in HD neuronal cultures. Pridopidine enhances brain-derived neurotrophic factor (BDNF) secretion, which is blocked by putative sigma-1 receptor antagonist NE-100, and was shown to upregulate transcription of genes in the BDNF, glucocorticoid receptor (GR), and dopamine D1 receptor (D1R) pathways in the rat striatum. The impact of different doses of pridopidine on gene expression and transcript splicing in HD across relevant brain regions was explored, utilizing the YAC128 HD mouse model, which carries the entire human mHtt gene containing 128 CAG repeats. RNAseq was analyzed from striatum, cortex, and hippocampus of wild-type and YAC128 mice treated with vehicle, 10 mg/kg or 30 mg/kg pridopidine from the presymptomatic stage (1.5 months of age) until 11.5 months of age in which mice exhibit progressive disease phenotypes. The most pronounced transcriptional effect of pridopidine at both doses was observed in the striatum with minimal effects in other regions. In addition, for the first time pridopidine was found to have a dose-dependent impact on alternative exon and junction usage, a regulatory mechanism known to be impaired in HD. In the striatum of YAC128 HD mice, pridopidine treatment initiation prior to symptomatic manifestation rescues the impaired expression of the BDNF, GR, D1R and cAMP pathways. Pridopidine has broad effects on restoring transcriptomic disturbances in the striatum, particularly involving synaptic transmission and activating neuroprotective pathways that are disturbed in HD. Benefits of treatment initiation at early disease stages track with trends observed in the clinic.
Comparative effectiveness of sentinel lymph node biopsy for patients with ductal carcinoma in situ.
Authors: Shi-Yi Wang, Pei-Yin Hung, Brigid K. Killelea, Sarah Schellhorn Mougalian, Suzanne B. Evans, Tannaz Sedghi, Cary Philip Gross
Journal: Journal of Clinical Oncology (2018)

e12602 Background: Although consensus guidelines recommend against the performance of sentinel lymph node biopsy (SLNB) in women with ductal carcinoma in situ (DCIS) undergoing breast conserving surgery (BCS), many patients still receive it. The purpose of this study was to examine benefits and harms associated with SLNB in this population. Methods: We identified women from the Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset aged 67–94 diagnosed 1998–2013 with DCIS who underwent BCS, with follow up through 2014. We assessed the incidence of subsequent mastectomy (measured by mastectomy that occurred more than 9 months after DCIS diagnosis, a proxy of recurrence), ipsilateral invasive breast cancer recurrence (reported by SEER), breast cancer mortality, and side effects (including lymphedema, wound infection, seroma, and pain). We used Mahalanobis matching and Cox proportional hazards models to estimate the associations between SLNB and outcomes. Statistical significance was determined by p-value < 0.01 due to multiple comparisons. Results: Our sample consisted of 12,553 beneficiaries with DCIS, 1,859 (14.8%) of whom underwent SLNB. After Mahalanobis matching (median follow-up of 50 months), SLNB was not associated with subsequent mastectomy (3.9% vs. 3.7%, p = .77), ipsilateral invasive cancer recurrence (2.9% vs 3.5%, p = .22), or breast cancer mortality (0.9% vs 0.7%, p = .542), but was significantly associated with lymphedema (6.0% vs 3.7%, p < .001) and seroma (9.4% vs 7.4%, p = .009). Multivariate analyses of the matched sample showed that SLNB use was not associated with the incidence of subsequent mastectomy (adjusted hazard ratio [AHR] 1.15; 99% confidence interval [CI] 0.78-1.67), ipsilateral invasive recurrence (AHR: 0.84; 99% CI 0.55-1.28), or breast cancer mortality (AHR: 1.24; 99% CI 0.55-2.81), but was significantly associated with occurrence of any side effects (AHR: 1.21; 99% CI 1.03-1.43), lymphedema (AHR: 1.31; 99% CI 1.04-1.65), and seroma (AHR: 1.31; 99% CI 1.02-1.69). Conclusions: Using SLNB to detect nodal involvement for older women with DCIS does not improve outcomes but leads to more side effects. Our findings suggest surgeons can safely avoid SLNB in this population.
Women’s Voices in Cardiology
Authors: Roxana Mehran
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
New Test Identifies <i>Candida auris</i>
Authors: Rebecca Voelker
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Clinical Trial Participants’ Views of the Risks and Benefits of Data Sharing
Authors: Michelle M. Mello, Van Lieou, Steven N. Goodman
Journal: New England Journal of Medicine (2018)

Sharing of participant-level clinical trial data has potential benefits, but concerns about potential harms to research participants have led some pharmaceutical sponsors and investigators to urge caution. Little is known about clinical trial participants' perceptions of the risks of data sharing.
Seeking a no-regrets decision: Women's rationale for choosing contralateral prophylactic mastectomy (CPM).
Authors: Diane Bloom, Stephanie B. Wheeler, Kandace P McGuire, Clara Lee, Kevin Weinfurt, Donald Rosenstein, Jennifer K Plichta, Eun-Sil Shelley Hwang
Journal: Journal of Clinical Oncology (2018)

152 Background: More women with early-stage unilateral breast cancer and low genetic risk are opting for CPM, despite their low risk of developing cancer in their healthy breast and evidence to demonstrate that CPM improves neither survival nor quality of life, while increasing the risk of surgical complications. Little is known about the factors that motivate this irreversible decision. Methods: We conducted comprehensive qualitative interviews with 42 women at low risk for contralateral breast cancer (CBC) who had CPM in the last 10 years. We recorded and transcribed the interviews and analyzed them using a grounded theory approach. Results: Contrary to hypotheses that newly diagnosed women overestimate their CBC risk, study patients knew of the low risk of cancer in their healthy breast, but still chose CPM. Statistics were unpersuasive; given healthy lifestyles and lack of risk factors, they felt unlucky to get breast cancer and feared they would be unlucky again. They believed CPM would give them more peace of mind and the fewest regrets should cancer return. Avoiding mammograms was important, given the potential for callbacks, biopsies, and more bad news. Avoiding radiation and wanting matching breasts were cited less often. Most were mainly focused on reducing their cancer risk and could not recall having critical information about CPM’s potential harms. A few knew of likely harms but misjudged their impact. When told of CPM’s higher risk of complications, most dismissed this as a disclaimer, believing they would get through surgery well. Despite experiencing negative effects of CPM, 38 of 42 stated they would make the same decision again. Conclusions: When choosing CPM, most women felt confident in making their decision, although many had incomplete knowledge of potential long-term impacts. Nevertheless the majority of women who chose CPM did not regret their decision, suggesting that women who elect CPM are selecting a treatment option that is consistent with their long-term personal values and preferences. While important to ensure women know potential long-term harms, our findings suggest they may not necessarily be dissuaded from CPM by more data, though they may be better prepared for it’s aftermath.
Frequency of locoregional recurrence among locally advanced HER2-positive breast cancer treated with modern multimodality therapy.
Authors: Lior Zvi Braunstein, Michelle Stempel, Emily Craig Zabor, Erin F. Gillespie, Atif J. Khan, Oren Cahlon, Beryl McCormick, Simon N. Powell, Monica Morrow
Journal: Journal of Clinical Oncology (2018)

e12604 Background: Prior to the advent of targeted therapies, patients with HER2-amplified (HER2+) breast cancers were at high risk for locoregional recurrence (LRR). The use of HER2 targeted therapy has rendered LRR uncommon among early-stage HER2+ patients. We sought to evaluate whether locally advanced breast cancer (LABC; AJCC Stage III) outcomes have improved similarly in the modern era. Methods: Patients treated for primary HER2+ LABC from 2006 to 2014 were identified from a prospectively-collected patient database. Clinicopathologic, treatment and response characteristics were analyzed for associations with local, regional and distant recurrence. Kaplan-Meier methods estimated time to recurrence and univariable Cox regression models were employed to identify predictors of outcome. Results: Among 241 patients with HER2+ LABC, the median age was 50 years, 68% had T2 or greater tumors and 88% had nodal metastases. 57% were estrogen receptor (ER) positive. 27% received neoadjuvant chemotherapy, 92% had anti-HER2 therapy (16% with dual-HER2 blockade), and 94% received radiotherapy. Pathologic complete response (pCR) was achieved in 28% of patients receiving neoadjuvant chemotherapy (n = 65). At a median follow-up of 4.5 years, 10 patients (4.1%) had isolated-LRRs and 50 (20.7%) developed distant metastases (DM). The 5-year probability of freedom from LRR was 94% (95%CI: 92–98%) and the 5-year DM-free rate was 76% (95%CI 70-83%). With few events, no clinicopathologic features were clearly associated with LRR, including age (p = 0.06), ER status (p = 0.65), or number of involved lymph nodes (p = 0.67). Among those receiving neoadjuvant chemotherapy, pCR was significantly associated with reduced risk of DM (HR = 0.2; p = 0.011); no LRR was observed among any patient with a pCR. Conclusions: In the setting of anti-HER2 therapy, patients presenting with locoregionally advanced HER2+ breast cancer exhibit excellent local and regional control, comparable to that of their early-stage counterparts. Long-term outcomes among this population are driven largely by systemic relapses, potentially limiting the yield of increasingly-aggressive locoregional therapies.
Analysis of psychosocial distress screening and needs assessment in adult survivors of childhood cancer.
Authors: Becky N. Lowry, Kyla Alsman, Susan Krigel, Wendy Hein, Hope Krebill, Gary C. Doolittle, Rebecca Mount, Caylin Shankweiler, Cheryl Gibson
Journal: Journal of Clinical Oncology (2018)

160 Background: Childhood cancer survivors (CCS) face complex psychological late effects. The need for systematic screening for psychosocial distress has been clearly identified; however, less clarity exists around characterizing factors that might identify patients at higher risk to support targeted treatment. The purpose of this study was to examine the results of psychological screening in a clinic for adult survivors of childhood cancer using the validated NCCN Distress Screening Thermometer and modified Needs Assessment and exploring the results with other patient factors. Methods: Retrospective chart review was completed on 117 CCS seen in our Survivorship Transition Clinic (STC) between 2014 and 2017. The NCCN Distress Thermometer and Needs Assessment were administered to patients attending the STC. Results were then analyzed with a number of additional factors to explore association. These factors included intensity of treatment (by Children’s Hospital of Philadelphia Intensity of Treatment Rating scale or ITR3), gender, and age at diagnosis. Results: Of 117 patients, 54 had low intensity ITR3 scores (1 or2) and 63 had high intensity ITR3 scores (3 or 4). Mean distress score was 2.669 for the group. A weak but statistically significant association existed between ITR3 scores and distress scale scores (r = 0.2, n = 117, p = 0.022). Mean distress scale scores did not differ between men (2.26 +/- 2.09) and women (2.92 +/- 2.6) nor were they significantly related to age at diagnosis (p = 0.242). Needs assessment identified emotional, nutritional, and physical as the most frequent concerns. Care needs mostly commonly identified were feeling anxious/worried/irritable, being concerned with weight control, or problems with pain / fatigue. Conclusions: While we did not identify statistically significant differences in distress based on gender or age at diagnosis, we did find weak statistical association between higher treatment intensity and higher distress scores. Needs assessment helped guide care plan development. As childhood cancer survivor rates increase, we have an obligation to evolve our understanding of not only physical late effects but also psychological late effects.
Noncigarette Tobacco Products—Gateway or Diversion?
Authors: Michelle Ip, Holly R. Middlekauff
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
PHYSIOLOGICAL STUDIES OF EXPERIMENTAL INSULIN AND METRAZOL SHOCK
Authors: D. W. LOUGHEED, G. EDWARD HALL
Journal: American Journal of Psychiatry (1939)

Some of the physiological and biochemical changes characteristically associated with the various specific stages of the convulsions produced by the intravenous injection of metrazol have been studied in unanæsthetized rabbits. The changes in the heart-rate, systemic and pulmonary blood pressure, splanchnic volume, respiration and blood gases are of sudden onset and of marked degree. The severity of these changes is such that the possibility of a hazard being associated with the clinical use of metrazol must be borne in mind.
The first new monotherapy therapeutic PBC study in a decade? An international study evaluating the faresoid C receptor agonist obeticholic acid in PBC
Authors: KV Kowdley, VA Luketic, DE Jones, RW Chapman, AK Burroughs, GM Hirschfield, R Poupon, C Schramm, C Vincent, C Rust, A Pares, AL Mason, EN Castelloe, CI Sciacca, O Boehm, M Pruzanski, DA Shapiro
Journal: Hepatology (2011)
‘Not all drugs (and route) are same’
Authors: Abhishek Arvind Zanwar
Journal: Annals of the Rheumatic Diseases (2018)

Not all drugs (and route) are same' I read with great interest, study by French vasculitis group, the MAINRITSAN 2 trial. 1 The results of this trial again underline our limitations for search of biomarker, which can predict relapse of antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis.I have few concerns about details and analysis regarding induction regime used in the patient study group.First is about the data provided by authors about the use of cyclophosphamide for remission induction.Previous study has shown that route and cumulative dose used for remission induction can affect relapse in long term. 2 Risk of relapse is significantly lower when daily oral cyclophosphamide was used for remission induction as against pulse intravenous cyclophosphamide.It would have been clearer if authors had given and compared details of cyclophosphamide therapy used for the last flare, especially when more than 60% of group of participants have received the drug.Second, a previous study has suggested that ANCA titres predicts relapse in patients in whom rituximab was used for remission induction but this observation was not seen in patient treated with cyclophosphamide. 3In current study group, use of cyclophosphamide was more frequent than rituximab, which may have affected results of study.May be subset analysis between these two groups can be more useful.
Enough Power to Build a Strong Case for Clinical Pharmacy Services?
Authors: Lorenz Van der Linden, Isabel Spriet, Jos Tournoy
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Prognosis in young women under 40 with brain metastasis from breast cancer.
Authors: Ariana Mustillo, Jean-Pierre M. Ayoub, Louise Yelle, Marie Florescu
Journal: Journal of Clinical Oncology (2018)

1091 Background: Breast cancer brain metastases in young women is doubly devastating as both quality of life and life expectancy are significantly reduced. With new radiation technology and drugs that have emerged survival of these young women is expected to increase Methods: Using OACIS and SARDO patient databases, we identified 121 patients diagnosed with breast cancer and brain metastasis at CHUM between 2006 and 2016. We divided our group into Group A: patients whose first metastasis was in the brain and Group B: patients who developed a brain metastasis during the evolution of the metastatic breast cancer. Then, we compared young patients < 40 to those ³ 40 for each category. Results: For the 121 patients with brain metastasis, the < 40 had a significantly longer mOS 18 mo compared to 4 mo for ³ 40 (P < 0.001). With respect to timing of brain metastasis, group A had also a significantly longer survival (7 months) than group B (4 months) (P = 0.032). For group A, 2years OS was 57% for patients < 40 vs 12% for patients ³ 40 (mOS NR vs 7 months; P = 0.259). For group B, patients < 40 had a significantly longer mOS 18mo than patients ³ 40y 3 mo (P = 0.0089). There was no statistically difference in groups regarding time to first metastasis. BRCA 1/2 mutations were known for only 23 of 121 patients (19%). The BRCA 1/2 positive patients (8/23 = 35%) were well distributed between both age groups and none were treated with PARP inhibitors. Conclusions: Young women with brain metastasis from breast cancer have a better prognosis than women³ 40. Patients who had their first metastasis to the brain also had a longer survival than patients whose metastasis to the brain developed later in the disease course.