tbuckley/cabot-search huggingface dataset:
Water Concentration Analysis of the Surgical Margin—Response
Authors: Gerwin J. Puppels
Journal: Cancer Research (2017)

In his letter, Dr. Murali refers to our recent publication in Cancer Research in which we used high-wave number Raman spectroscopy to show that Raman spectroscopy can be used for demarcation of the tumor border, which is a pressing clinical need.Therefore, our work addresses a situation in which it has already been established that a tumor is present and that it needs to be surgically removed. When the aim is cure, it means the patient benefits from a complete resection of the tumor with adequate margins between the resection surface and the tumor.We fully concur with Dr. Murali that in principle, the fingerprint region contains more spectroscopic information and that it might be advantageous to use also this part of the Raman spectrum if otherwise the clinical goal cannot be achieved.We disagree that our results are in contrast with Dr. Murali's findings. If high-wave number Raman spectroscopy suffices to reach the intended clinical goal, then there is absolutely no reason to make the instrumentation more complex by also adding the fingerprint region. Complexity will get in the way of actual translation into clinical practice, and it will take longer before Raman technology reaches the clinic for the benefit of patients.The spectra included in the letter of Dr. Murali are ample evidence of this. They contain instrumentation artifacts and as a consequence are hardly recognizable as Raman spectra. In the fingerprint region, we assume this is due to filtering artifacts in the fiber optics and/or to background subtraction artifacts. In the high-wave number region, half of the waterband is missing due to spectrometer/detector limitations. So also for this reason, these results cannot serve as a sound comparison with our results.See the original Letter to the Editor, p. 3121G.J. Puppels is the managing director at and has ownership interest (including patents) in RiverD International B.V. No other potential conflicts of interest were disclosed.
Abstract 244: A Novel Method for the Generation of Induced Pluripotent Stem Cells From Human Peripheral Blood
Authors: Han-Mo Yang, Ju-Young Kim, Yoo-Wook Kwon, Hyo-Soo Kim
Journal: Circulation Research (2015)

Background: In terms of the generation of induced pluripotent stem(iPS) cells, one of the important issues for clinical applications is cell source. Human peripheral blood is one of the easily accessible cell sources. However, isolated peripheral blood cells have shown low gene transfection efficiency and inconveniences requiring specific methods to isolate. Here, we report a novel population of peripheral blood-derived stem cells, which can be easily reprogrammed to iPS cells. Methods and Results: We cultured peripheral blood mononuclear cells (PBMC) from human peripheral blood and seeded on the fibronectin-coated plate. We observed adherent cells from as early as 5 days after the start of culture and those cells gradually formed colonies. We were able to isolate these cells with very high efficiency. Furthermore, we have also confirmed that these cells can be differentiated to osteogenic, adipogenic, and myogenic-lineage cells. Therefore, we named these cells circulating multipotent adult stem cell. We were successful in generating iPS cells with these cells. These cells showed enhanced efficiency of gene transduction, compared to the human dermal fibroblast. We obtained reprogrammed colonies in 8 days after 4 factor virus transduction without feeder cells. We identified our iPS cells had similar features to embryonic stem cell in morphology, gene expression, epigenetic state and ability to differentiate into the three germ layers. We obtained more than 46 iPS cell lines from PBMC of patients with cardiovascular disease and normal volunteers. Conclusions: Our study showed new methods to isolate stem cells from peripheral blood and to generate iPS cells with high efficacy. This result suggests that our new approach could be one of ideal methods for clinical application of iPS cells in future.
Efficacy of Octreotide in the Therapy of Severe Nonproliferative and Early Proliferative Diabetic Retinopathy: A Randomized Controlled Study
Authors: Karen M. Gehrs
Journal: Diabetes Care (2001)

I read with interest the article by Grant et al. (1) regarding the effects of octreotide on severe nonproliferative and early proliferative diabetic retinopathy. However, I have a few observations and questions for Grant et al. First, I noticed that the baseline Early Treatment of Diabetic Retinopathy Study (ETDRS) scores of the two groups were not compared. Did these two groups have baseline ETDRS scores that were not significantly different? The results of the study cannot be interpreted without the knowledge of the baseline ETDRS scores of the two groups. In addition, …
Comparison of artemether-lumefantrine and chloroquine with and without primaquine for the treatment of Plasmodium vivax infection in Ethiopia: A randomized controlled trial
Authors: Tesfay Abreha, Jimee Hwang, Kamala Thriemer, Yehualashet Tadesse, Samuel Girma, Zenebe Melaku, Ashenafi Assef, Moges Kassa, Mark D. Chatfield, Keren Z. Landman, Stella M. Chenet, Naomi W. Lucchi, Venkatachalam Udhayakumar, Zhiyong Zhou, Ya Ping Shi, S. Patrick Kachur, Daddi Jima, Amha Kebede, Hiwot Solomon, Addis Mekasha, Bereket Hailegiorgis Alemayehu, Joseph L. Malone, Gunewardena Dissanayake, Hiwot Teka, Sarah Auburn, Lorenz von Seidlein, Ric N. Price
Journal: PLoS Medicine (2017)

Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia.Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia.Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y.ClinicalTrials.gov NCT01680406.
Obstructive Sleep Apnea
Authors: Jay S. Balachandran, Sanjay R. Patel
Journal: Annals of Internal Medicine (2014)

This issue provides a clinical overview of Obstructive Sleep Apnea focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.
Inflammatory Markers and Onset of Cardiovascular Events
Authors: Matteo Cesari, Brenda W.J.H. Penninx, Anne B. Newman, Stephen B. Kritchevsky, Barbara J. Nicklas, Kim Sutton-Tyrrell, Susan M. Rubin, Jingzhong Ding, Eleanor M. Simonsick, Tamara B. Harris, Marco Pahor
Journal: Circulation (2003)

Inflammation plays an important role in cardiovascular disease. The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons.The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study. Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 3.6 years. Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were assessed. After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 1.27; 95% CI, 1.10 to 1.48; stroke events, per IL-6 SD increase: RR, 1.45; 95% CI, 1.12 to 1.86; CHF events, per IL-6 SD increase: RR, 1.72; 95% CI, 1.40 to 2.12). TNF-alpha showed significant associations with CHD (per TNF-alpha SD increase: RR, 1.22; 95% CI, 1.04 to 1.43) and CHF (per TNF-alpha SD increase: RR, 1.59; 95% CI, 1.30 to 1.95) events. CRP was significantly associated with CHF events (per CRP SD increase: RR, 1.48; 95% CI, 1.23 to 1.78). A composite summary indicator of inflammation showed a strong association with incident cardiovascular events, with an especially high risk if all 3 inflammatory markers were in the highest tertile.Findings suggest that inflammatory markers are independent predictors of cardiovascular events in older persons.
Falls, Functioning, and Disability Among Women With Persistent Symptoms of Chemotherapy-Induced Peripheral Neuropathy
Authors: Kerri M. Winters-Stone, Fay Horak, Peter G. Jacobs, Phoebe Trubowitz, Nathan F. Dieckmann, Sydnee Stoyles, Sara Faithfull
Journal: Journal of Clinical Oncology (2017)

Purpose Chemotherapy-induced peripheral neuropathy (CIPN) may persist after treatment ends and may lead to functional decline and falls. This study compared objective and self-report measures of physical function, gait patterns, and falls between women cancer survivors with and without symptoms of CIPN to identify targets for functional rehabilitation. Methods A secondary data analysis of 512 women cancer survivors (age, 62 ± 6 years; time since diagnosis, 5.8 ± 4.1 years) categorized and compared women self-reporting symptoms of CIPN (CIPN+) with asymptomatic women (CIPN-) on the following: maximal leg strength, timed chair stand, physical function battery, gait characteristics (speed; step number, rate, and length; base of support), self-report physical function and disability, and falls in the past year. Results After an average of 6 years after treatment, 47% of women still reported symptoms of CIPN. CIPN+ had significantly worse self-report and objectively measured function than did CIPN-, with the exception of maximal leg strength and base of support during a usual walk. Gait was slower among CIPN+, with those women taking significantly more, but slower and shorter, steps than did CIPN- (all P < .05). CIPN+ reported significantly more disability and 1.8 times the risk of falls compared with CIPN- ( P < .0001). Increasing symptom severity was linearly associated with worsening function, increasing disability, and higher fall risk (all P < .05). Conclusion This work makes a significant contribution toward understanding the functional impact of CIPN symptoms on cancer survivors. Remarkably, 47% of women in our sample had CIPN symptoms many years after treatment, together with worse function, greater disability, and more falls. CIPN must be assessed earlier in the clinical pathway, and strategies to limit symptom progression and to improve function must be included in clinical and survivorship care plans.
A heparin conjugate, LHbisD4, inhibits lymphangiogenesis and attenuates lymph node metastasis by blocking VEGF-C signaling pathway
Authors: Jeong Uk Choi, Seung Woo Chung, Taslim A. Al-Hilal, Farzana Alam, Jooho Park, Foyez Mahmud, Jee-Heon Jeong, Sang Yoon Kim, Youngro Byun
Journal: Biomaterials (2017)
Blunted Counterregulatory Hormone Responses to Hypoglycemia in Young Children and Adolescents With Well-Controlled Type 1 Diabetes
Authors: Eva Tsalikian, William Tamborlane
Journal: Diabetes Care (2010)

We thank Graveling et al. (1) for their thoughtful comments regarding our article (2). In their letter, they argue that our conclusion was not supported by the study data because the achieved level of hypoglycemia was not adequate. They point out that the mean nadir plasma glucose level in our subjects was ∼60 mg/dl, whereas plasma glucose concentrations <60 mg/dl are often required to elicit …
Keratinocyte growth factor for the treatment of the acute respiratory distress syndrome (KARE): a randomised, double-blind, placebo-controlled phase 2 trial
Authors: Daniel F McAuley, LJ Mark Cross, Umar Hamid, Evie Gardner, J Stuart Elborn, Kathy M Cullen, Ahilanandan Dushianthan, Michael PW Grocott, Michael A Matthay, Cecilia M O'Kane
Journal: The Lancet Respiratory Medicine (2017)
급성 A형간염에 의한 간내 강성도의 변화
Authors: 서연석 ( Yeon Seok Seo ), 엄순호 ( Soon Ho Um ), 서상준 ( Sang Jun Suh ), 정은석 ( Eun Suk Jung ), 장진수 ( Jin Su Jang ), 권용대 ( Yong Dae Kwon ), 박상훈 ( Sang Hoon Park ), 금보라 ( Bo Ra Keum ), 김용식 ( Yong Sik Kim ), 진윤태 ( Yoon Tae Jeen ), 전훈재 ( Hoon Jai Chun )
Journal: Clinical and Molecular Hepatology (2008)

목적: 만성 간염 환자에서 liver stiffness (LS) 측정이 간섬유화를 평가하는 데 매우 유용한 검사로 알려져 있으나, 일부 환자에서는 LS와 실제 간섬유화 단계 사이에 상당한 차이가 관찰된다. 본 연구는 간의 괴사염증 정도가 이런 두 검사 결과 사이의 차이에 관여하는가를 평가하기 위해 시행하였다. 대상과 방법: 급성 A형간염으로 본원에 입원한 환자를 대상으로 하였다. 입원 후 환자의 혈청 ALT 수치와 bilirubin 수치의 변화에 따라 환자의 입원 당시 급성 A형간염의 단계를 염증단계, 황달단계 및 회복단계로 분류하였으며, 회복단계에서 입원한 환자(입원 후 ALT 및 bilirubin 수치가 계속 감소하는 경우)는 본 연구에서 제외하였다. 입원 시 LS를 측정하였으며 상태가 호전되어 퇴원한 후 추적하였다. LS값과 급성 A형간염의 진행단계, LS 측정 당시의 혈청 AST, ALT 및 bilirubin 수치와의 상관관계를 분석하였다. 결과: 76명의 급성 A형간염 환자가 본 연구에 포함되었으며 연령의 중앙값은 29세였다(남자 46명 여자 30명). 이들 중 33명(43.4%)은 염증단계에, 43명(56.6%)은 황달단계에 입원하였다. 염증단계에 입원한 33명에서 급성 A형간염의 증상이 발생한 후 혈청 ALT가 최고치에 도달할 때까지의 기간은 7±3일이었으며, 전체 대상 환자에서 증상이 발생한 후 bilirubin이 최고치에 도달할 때까지의 기간은 11±4일이었다. 입원 중 측정한 LS값은 8.9±3.3 kPa였다. LS값은 bilirubin 수치와만 상관관계를 보였으며, LS 상승(>7.08 kPa)과 관련이 있는 인자도 bilirubin 수치뿐이었다. 급성 간염의 증상이 발생한 후 LS값은 점차 상승하다가 증상 발생 후 8~9일 정도에 최고치에 도달한 후 점차 감소하였다. 결론: 심한 간의 괴사염증은 LS를 높여 간섬유화 단계를 실제보다 과대평가할 수 있으므로 급성 악화를 동반한 만성간염 환자에서 LS를 측정한 경우 결과의 판정에 유의하여야 할 것으로 생각된다.
Abstract 233: Isoproterenol-induced Cardiac Hypertrophy And Failure In Mice: Gene Network Modeling
Authors: Christoph D Rau, Jessica Wang, Shuxun Ren, Zhihua Wang, Hongmei Ruan, Yibin Wang, Aldons J Lusis
Journal: Circulation Research (2013)

Heart failure is highly heterogeneous and as a result, relatively few insights into the pathways and drivers of heart failure have been identified using system-wide methods such as genome-wide association studies (GWAS). We have developed a resource, the Hybrid Mouse Diversity Panel (HMDP) for high resolution GWAS and systems genetics in mice. Eight week old female mice from 93 unique inbred strains of the HMDP were given 20 μg/g/day of isoproterenol through an abdominally implanted Alzet micropump. Three weeks post-implantation, all mice were sacrificed, along with age-matched controls. The mice exhibited widely varying degrees of hypertrophy and heart functioning. A portion of the left ventricle was processed and arrayed on an Illumina Mouse Ref 8.0 platform. We used Maximal Information Component Analysis, a novel method of network construction which allows for non-linear relationships between genes as well as non-binary partitioning of genes into sub-networks to subdivide the expression data into a series of modules. In order to identify modules which may contribute to Isoproterenol-induced hypertrophy and failure, we examined the correlation of each module to clinically relevant cardiac traits traits such as organ weights and echocardiographic parameters. We identified several modules with strong correlations to multiple heart failure-related clinical traits, including one module of 41 genes which contained several genes of interest, including Lgals3, a diagnostic marker for heart failure. Utilizing eQTL hotspot analysis, we have identified a locus which is involved in the regulation of this module. A gene within this locus, Magi2, regulates the turnover of the β-adrenergic receptor and represents a likely candidate for the response to isoproterenol.
Correlation of immune phenotype with IDH mutation in diffuse glioma
Authors: Anna Sophie Berghoff, Barbara Kiesel, Georg Widhalm, Dorothee Wilhelm, Orsolya Rajky, Sebastian Kurscheid, Philip Kresl, Adelheid Wöhrer, Christine Marosi, Monika E Hegi, Matthias Preusser
Journal: Neuro-Oncology (2017)

Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors.Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database.TIL and PD-L1 expression were observed in approximately half of WHO grade II/III gliomas. IDH-wt status was associated with significantly higher TIL infiltration and PD-L1 expression among all (grades II-IV) cases (n = 174, P < 0.001) and within the cohort of glioblastomas (n = 131, P < 0.001). In low-grade glioma (LGG) and glioblastoma cohorts of TCGA, significantly higher PD-L1 gene expression levels were evident in IDH-wt compared with IDH-mut samples (LGG: N = 516; P = 1.933e-11, GBM: N = 161; P < 0.009). Lower PD-L1 gene expression was associated with increased promoter methylation (Spearman correlation coefficient -0.36; P < 0.01) in the LGG cohort of TCGA. IDH-mut gliomas had higher PD-L1 gene promoter methylation levels than IDH-wt gliomas (P < 0.01).The immunological tumor microenvironment of diffuse gliomas differs in association with IDH mutation status. IDH-wt gliomas display a more prominent TIL infiltration and higher PD-L1 expression than IDH-mut cases. Mechanistically this may be at least in part due to differential PD-L1 gene promoter methylation levels. Our findings may be relevant for immune modulatory treatment strategies in glioma patients.
Skin and subcutaneous tissue disorders (SSTDs) in patients (pts) with HER2-positive metastatic breast cancer (MBC) in the phase III trial CLEOPATRA of pertuzumab or placebo with trastuzumab and docetaxel.
Authors: David Miles, Andrea Lacasia, Luen Lee, Kenneth Dana, Sarah Heeson, Adam Knott, Chia C. Portera, Sandra M. Swain
Journal: Journal of Clinical Oncology (2015)

598 Background: CLEOPATRA established pertuzumab (P), trastuzumab (T), and docetaxel (D) as the first-line standard of care for pts with HER2-positive MBC. SSTDs were often observed in CLEOPATRA. We report detailed analyses of SSTDs from this phase III study. Methods: The safety population in this analysis included 396 pts in the placebo (Pla) arm (Pla+T+D) and 408 pts in the pertuzumab arm (P+T+D). SSTDs included rash (group term), pruritus, dry skin, alopecia, and nail disorders; incidence, severity (NCI-CTCAE v3.0), management, and outcome were analyzed in both treatment (tx) arms. Results: See table. The most common grade ≥ 3 SSTD in both arms of the study was rash before and after D discontinuation. Median time to onset of SSTDs was 22 days (Pla+T+D) and 20 days (P+T+D). Median duration of SSTDs was 121 days (Pla+T+D) and 96 days (P+T+D). SSTDs required medical tx in 33.8% (Pla+T+D) and 45.9% (P+T+D) of pts. Steroids were frequently used for tx of rash, antibiotics for nail disorders, and antihistamines for pruritus. Repeated episodes of any SSTD occurred in 17% (Pla+T+D) and 26% (P+T+D) of pts. SSTDs led to discontinuation of all study tx in 0.3% (Pla+T+D) and 0.2% (P+T+D) of pts; and discontinuation of D alone in 1.0% (Pla +T+D) and 3.7% (P+T+D) of pts. Conclusions: SSTDs were common in both Pla+T+D and P+T+D arms, although more frequent during D therapy. SSTDs were mostly low-grade, manageable, and rarely resulting in tx discontinuation. There is no specific tx for SSTDs and tx should be empirical, depending on the nature of the SSTD. These results will further inform clinicians on the nature and management of SSTDs for pts who receive P+T+D for the tx of HER2-positive MBC. Clinical trial information: NCT00567190. Incidence of SSTDs. All grades and most common (≥ 10 or 5%) and grade ≥ 3 (total) SSTDs Overall Exposure to Study Tx ≥ 10% After D Discontinuation ≥ 5% AE n(%) Pla+T+D n = 396 P+T+D n = 408 AE n(%) Pla+T+D n = 267 P+T+D n = 311 Alopecia 240 (60.6) 248 (60.8) Rash 21 (7.9) 56 (18.0) Rash 95 (24.0) 153 (37.5) Pruritus 15 (5.6) 42 (13.5) Nail disorder 93 (23.5) 96 (23.5) Nail disorder 13 (5.0) 13 (4.2) Pruritus 40 (10.1) 72 (17.6) Dry skin 24 (6.1) 46 (11.3) Grade ≥ 3 SSTDs 8 (2.0) 18 (4.4) 1 (0.4) 2 (0.6)
The Treatment of Hyperthyroidism
Authors: E. M. Chapman
Journal: New England Journal of Medicine (1961)

Iodine and Antithyroid DrugsIodine (I127) as a therapeutic agent in hyperthyroidism received thorough investigation and clinical trial3 between 1923 and 1943, and yet it cannot be considered a definitive form of therapy. Its oral administration produces a more rapid clinical action than any other medicine, but the effects are usually transitory. There is no advantage in excessive dosage, and maximal response may be obtained by 10 drops of saturated solution of potassium iodide (500 mg. of iodine) given once daily. Rarely does the disease go into long remission on iodine therapy alone. Symptomatic improvement with iodine begins in . . .