tbuckley/cabot-search huggingface dataset:
A Longitudinal Study of Peripubertal Serum Organochlorine Concentrations and Semen Parameters in Young Men: The Russian Children’s Study
Authors: Lidia Mínguez-Alarcón, Oleg Sergeyev, Jane S. Burns, Paige L. Williams, Mary M. Lee, Susan A. Korrick, Luidmila Smigulina, Boris Revich, Russ Hauser
Journal: Environmental Health Perspectives (2016)

Exposures to endocrine-disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters.We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men.From 2003 through 2005, 516 boys were enrolled at age 8-9 years and followed for up to 10 years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At 18-19 years, 133 young men provided 1 or 2 semen samples (256 samples) collected approximately 1 week apart, which were analyzed for volume, sperm concentration, and motility. Unadjusted and adjusted linear mixed models were used to examine the associations of quartiles of lipid-standardized concentrations of dioxins [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated dibenzo-p-dioxins (PCDDs)], furans, polychlorinated biphenyls (PCBs), and corresponding toxic equivalents (TEQs) with semen parameters.The median (range) for TCDD was 2.9 (0.4-12.1) pg/g lipid and PCDD TEQ was 8.7 (1.0-36.0) pg TEQ/g lipid. Higher quartiles of TCDD and PCDD TEQs were associated with lower sperm concentration, total sperm count, and total motile sperm count (p-trends ≤ 0.05). The highest quartile of peripubertal serum TCDD concentrations was associated with a decrease (95% CI) of 40% (18, 66%), 29% (3, 64%), and 30% (2, 70%) in sperm concentration, total sperm count, and total motile sperm count, respectively, compared with the lowest quartile. Similar associations were observed for serum PCDD TEQs with semen parameters. Serum PCBs, furans, and total TEQs were not associated with semen parameters.Higher peripubertal serum TCDD concentrations and PCDD TEQs were associated with poorer semen parameters. Citation: Mínguez-Alarcón L, Sergeyev O, Burns JS, Williams PL, Lee MM, Korrick SA, Smigulina L, Revich B, Hauser R. 2017. A longitudinal study of peripubertal serum organochlorine concentrations and semen parameters in young men: the Russian Children's Study. Environ Health Perspect 125:460-466; http://dx.doi.org/10.1289/EHP25.
Weekly Carfilzomib, Cyclophosphamide and Dexamethasone (wCCyd) in Elderly Newly Diagnosed Multiple Myeloma Patients: Results of a Phase 2 Study
Authors: Sara Bringhen, Davide Rossi, Alessandra Larocca, Paolo Corradini, Piero Galieni, Alessandra Malfitano, Simona Aschero, Massimo Offidani, Anna Marina Liberati, Mariella Genuardi, Gianluca Gaidano, Carmela Palladino, Fabiana Gentilini, Mario Boccadoro, Pieter Sonneveld, Antonio Palumbo
Journal: Blood (2015)
The role of radiation therapy as part of local-regional treatment in breast cancer patients with metastatic disease at diagnosis
Authors: W. Khodari, A. Vataire, S. Delaloge, F. André, C. Uzan, J. Garbay, A. Dunant, R. Arriagada, H. Marsiglia, C. Bourgier
Journal: Journal of Clinical Oncology (2008)

1085 Background: Until recently, patients (pts) with stage IV breast cancer at diagnosis (BC) were generally treated with exclusive systemic therapy. There is recent retrospective evidence of the potential benefits of local surgery as part of the treatment plan. We attempted to evaluate, in a large retrospective series, local control (LC) rates achieved by loco-regional radiation therapy (LRRT) alone or in combination with surgery. Methods: We retrospectively reviewed the prospectively registered data of all pts treated at the Institut Gustave Roussy since 1990, for BC with evidence of distant metastases at diagnosis and who have received a loco-regional treatment. Survival curves were determined by the Kaplan-Meier method and Cox models were used for adjusted comparisons. Results: Between 1990 and 2003, 239 BC pts met the inclusion criteria. Median follow-up 6.5 years, median age: 55 years; ER-positive 68%, visceral metastases 51%. Primary chemotherapy was given in 86% of pts. Pts were categorized for loco-regional treatment as having received LRRT only (group 1; n=147) or breast and axillary surgery ± LRRT (group 2; n=92). Hormone therapy was given in 57% of ER positive BC pts until disease progression. LC rates at 3-years FU, metastases-progression-free survival (MPFS) and overall survival (OS) rates are shown in Table 1. Conclusions: Our results suggest that loco-regional treatment is an important part of the treatment of BC pts with metastases at diagnosis. Radiation therapy alone or in association with surgery provides an excellent local control. Better MPFS and OS rates in group 2 may be related to more favorable prognostic factors at diagnosis influencing the treatment choice. Group 1 LRRT Group 2 Surgery Hazard ratio of event in the surgery vs LRRT group (95% confidence interval) * p Number of patients 147 92 >1 metastase site 41% 21% 0.0009 Median tumor size (mm) 60 45 0.05 >N1 32% 16% 0.007 Grade 3 43% 31% 0.08 LC 89% 91% 3.07 (0.94;10.05)* 0.06* MPFS 20% 39% 1.05 (0.72;1.53)* 0.82* OS 39% 57% 1.05 (0.70;1.57)* 0.83* * Adjusted on prognostic factors No significant financial relationships to disclose.
Case 33-1972
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Bernard M. Jacobson, Robert E. Scully
Journal: New England Journal of Medicine (1972)

Presentation of CaseA 67-year-old man was admitted to the hospital because of lymphadenopathy.He had been well until one month previously, when anorexia and right-sided abdominal pain developed, followed by the passage of grossly bloody stools. On admission to the hospital physical examination was negative except that the edge of the liver was felt 2 cm below the right costal margin. Extensive studies, including sigmoidoscopic examination, an air-contrast barium-enema examination and a gastrointestinal series, revealed only an axial hiatus hernia and a few diverticula of the sigmoid colon. Pyuria was found, and culture of the urine yielded an abundant . . .
Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia
Authors: Xiaoli Wei, Jie Gao, Ronnie H. Fang, Brian T. Luk, Ashley V. Kroll, Diana Dehaini, Jiarong Zhou, Hyeon Woo Kim, Weiwei Gao, Weiyue Lu, Liangfang Zhang
Journal: Biomaterials (2016)
First line with paclitaxel dose dense in patients with advanced soft tissue sarcoma (aSTS): Phase II, prospective trial—National Medical Center “20 Noviembre”, ISSSTE, México.
Authors: Josue Mora Perez, Fernando Aldaco, Guadalupe Cervantes, Aura Valles, Laura Torrecillas
Journal: Journal of Clinical Oncology (2016)

e22532 First line with paclitaxel dose dense in patients with advanced soft tissue sarcoma (aSTS): Phase II, prospective trial. National Medical Center “20 Noviembre”, ISSSTE. México. Background: With limited efficacy, first line chemotherapy has not been changed in the last 30 years. Dose dense chemotherapy increase overall survival and progression free survival in some types of cancer (breast and ovarian cancer). Hypothetically, dose dense chemotherapy could achieve better outcomes in soft tissue sarcomas; however, dose dense doxorubicin failed to improve disease control in aSTS. We evaluated an alternative regimen with dose dense paclitaxel in patients who were not candidates for conventional doxorubicin. Methods: This is an open label, single center/arm prospective trial, approved by local ethics committee. Informed consent was obtained for all subjects. Inclusion criteria: Pts with metastatic or recurrent soft tissue sarcoma, naïve chemotherapy, ECOG 0-2, measurable lesion, adequate organ function. Treatment: Paclitaxel 175 mg/m2 d1, q2w up to 10 cycles plus filgrastim 300 mcg d2-5. Primary endpoint: Response rate (assessed every 4 weeks) and safety. Secondary end point: PFS and overall survival. Results: From Sep 2104 – Jun 2015 nine pts were enrolled, median age was 54y (38-71), female 77%, ECOG 0/1 88%, STS Grade 3: 66%, liposarcoma 33%, Leiomyosarcoma 33%, MHF 22%, other 11%. Efficacy: complete or partial response 0%, stable disease 33%, Progression disease 64%. Median number of cycles: 6 (2-10). Dose intensity 100%. Toxicity G1/2: alopecia 100%, neuropathy 40%. PFS 2.1m (1-12m), overall survival 7.1m (89% pts received pegylated liposomal doxorubicin as second line). Efficacy Liposarcoma (3 pts): stable disease 100%, PFS 8.6m, and overall survival: NR Conclusions: Paclitaxel Dose dense showed a disappointing progression free survival and response rate as first line chemotherapy in pts with aSTS. Recruitment was stopped after the first interim analysis. Dose dense paclitaxel showed some level of activity in liposarcoma and could be evaluated in furthers studies
Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine and Melphalan (FM) Reduced Intensity Conditioning (RIC) for High-Risk AML/MDS.
Authors: B. Oran, R. Saliba, S. Giralt, D. Couriel, A. Carrasco-Yalan, C. Hosing, M. Shahjahan, E. de Meis, A. Anagnostopoulos, P. Anderlini, S. Ghosh, I. Khouri, R. Champlin, M. de Lima
Journal: Blood (2005)
Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic Spectrum
Authors: Elena J. Tucker, Sonia R. Grover, Anne Bachelot, Philippe Touraine, Andrew H. Sinclair
Journal: Endocrine Reviews (2016)

Premature ovarian insufficiency (POI) is one form of female infertility, defined by loss of ovarian activity before the age of 40 and characterized by amenorrhea (primary or secondary) with raised gonadotropins and low estradiol. POI affects up to one in 100 females, including one in 1000 before the age of 30. Substantial evidence suggests a genetic basis for POI; however, the majority of cases remain unexplained, indicating that genes likely to be associated with this condition are yet to be discovered. This review discusses the current knowledge of the genetic basis of POI. We highlight genes typically known to cause syndromic POI that can be responsible for isolated POI. The role of mouse models in understanding POI pathogenesis is discussed, and a thorough list of candidate POI genes is provided. Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.
Spinal cord injury induces astroglial conversion towards neuronal lineage
Authors: Harun Najib Noristani, Jean Charles Sabourin, Hassan Boukhaddaoui, Emilie Chan-Seng, Yannick Nicolas Gerber, Florence Evelyne Perrin
Journal: Molecular Neurodegeneration (2016)

Neurons have intrinsic capability to regenerate after lesion, though not spontaneously. Spinal cord injury (SCI) causes permanent neurological impairments partly due to formation of a glial scar that is composed of astrocytes and microglia. Astrocytes play both beneficial and detrimental roles on axonal re-growth, however, their precise role after SCI is currently under debate.We analyzed molecular changes in astrocytes at multiple stages after two SCI severities using cell-specific transcriptomic analyses.We demonstrate that astrocyte response after injury depends on both time after injury and lesion severity. We then establish that injury induces an autologous astroglial transdifferentiation where over 10 % of astrocytes express classical neuronal progenitor markers including βIII-tubulin and doublecortin with typical immature neuronal morphology. Lineage tracing confirmed that the origin of these astrocytes is resident mature, rather than newly formed astrocytes. Astrocyte-derived neuronal progenitors subsequently express GABAergic, but not glutamatergic-specific markers. Furthermore, we have identified the neural stem cell marker fibroblast growth factor receptor 4 (Fgfr4) as a potential autologous modulator of astrocytic transdifferentiation following SCI. Finally, we establish that astroglial transdifferentiation into neuronal progenitors starts as early as 72 h and continues to a lower degrees up to 6 weeks post-lesion.We thus demonstrate for the first time autologous injury-induced astroglial conversion towards neuronal lineage that may represent a therapeutic strategy to replace neuronal loss and improve functional outcomes after central nervous system injury.
Clinical approach to non-neutropenic fever in pediatric oncology patients.
Authors: Raya Hamad Saab, Bilal Ali Abou Ali, Nader Hirmas, Rima Hanna Wakim, Samar Muwakkit, Miguel Abboud, Hassan Mohamed El Solh
Journal: Journal of Clinical Oncology (2014)

e21031 Background: There are no clear guidelines on standard management of fever in non-neutropenic pediatric oncology patients. Methods: We analyzed the clinical characteristics and outcome of febrile non-neutropenic episodes in pediatric oncology patients at a single institution in Lebanon in 2012. Results: A total of 151 episodes occurred in 45 patients. Twenty episodes (13%) were triaged as high-risk and directly admitted for inpatient administration of broad-spectrum antibiotics. These included 11 patients presenting with sepsis, 5 presenting with fever during induction phase for acute leukemia, and 4 presenting with concomitant vomiting and/or diarrhea requiring intravenous hydration. In this “high-risk” group, 4 had positive blood cultures (20%). The remaining 131 patients were triaged as “low-risk”, and managed with once daily intravenous Ceftriaxone in outpatient setting. Of those, two patients (1.5%) had bacteremia (S. pneumoniae, and S. epidermidis). Notably, 27 patients (20%) were eventually admitted for inpatient management: 14 (10%) for a localized infection, 9 (7%) for febrile neutropenia, and 4 (3%) for positive urine culture for resistant organisms requiring inpatient antibiotic regimens. Other suspected infections included upper respiratory tract in 33 (25%), acute otitis media in 9 (7%), tonsillitis in 8 (6%), and gastroenteritis in 6 (4%), while no focus was identified in 48 (36%). Notably, there were 18 positive urine cultures (14%) by clean-catch specimen, ranging from 1,100 to 100,000 CFU/ml, of unknown clinical significance. In addition, 6 patients (4.6%) had a single positive blood culture for skin flora, judged to be skin contaminants not warranting further therapy. Conclusions: Clinically significant bacteremia occurred in 20% (4/20) of high-risk triaged episodes, and 1.5% (2/131) low-risk triaged episodes. 20% of low-risk triaged episodes eventually led to admission, suggesting that close follow-up and empiric treatment may be indeed warranted for this population. We also found frequent positive urine cultures of undetermined significance, raising the need for further investigation of this finding, to avoid overtreatment and emergence of resistant organisms.
Severe drug interactions and potentially inappropriate medication usage in elderly patients with cancer.
Authors: Ali Alkan, Arzu Yasar, Ebru Karcı, Elif Berna Koksoy, Muslih Urun, Filiz Cay Senler, Yuksel Urun, Hakan Ergun, Hakan Akbulut
Journal: Journal of Clinical Oncology (2016)

10056 Background: Due to more comorbidities, polypharmacy is common in elderly patients and drug interactions are inevitable. Prevalence and clinical impacts of drug interactions and using potentially inappropriate medications (PIM) have been studied in geriatric patients. However, these are not well defined in oncology practice. The purpose of this study is to define the prevalence of PIMs and drug interactions (DIs) in elderly cancer patients and investigate the factors associated with them Methods: Patients more than 65 years of age in both inpatient and outpatient clinics were evaluated. Patient, disease characteristics and medications used were collected by self reports and medical records. Drug interactions were checked and PIM was defined with 2012 update of Beers criteria. Severe drug interactions are defined with category D or X DIs. Results: 445 elderly patients (286 outpatient, 159 inpatient), with a median age of 70 (65- 89) were evaluated. Severe DIs were present in 156(35.1%) of patients, 81(28.3%) and 75(47.2%) for outpatient and inpatients, respectively (p<0.001). PIMs were present in 117(26.6%) of the patients, 40(14.2%) and 77(48.4%) for outpatient and inpatients, respectively (p<0.001). In multivariate analysis; polypharmacy (≥5 drugs), inpatient status and diagnosis of lung cancer were associated with severe DIs. Polypharmacy, inpatient status and bad performance score (ECOG 3-4) were associated with PIMs (Table). Conclusions: Nearly one third of the elderly cancer patients are exposed to severe drug interactions and PIMs. More strategies should be developed in this group of patients to minimize the medications prescribed and prevent severe DIs. Multivariate analysis of factors associated with D or x category drug interaction and PIM usage. D or X interaction PIM OR CI (95%) p OR CI (95%) p Polypharmacy 3.8 2.3- 6.3 <0.001 3.8 2.1- 6.9 <0.001 Inpatient 2.7 1.4- 4.9 0.001 5.3 2.7- 10.5 <0.001 Performance score (3-4) 1.4 0.6- 3.4 0.43 3.5 1.4- 8.4 0.005 Lung Cancer 2.1 1.2- 3.6 0.006 Comorbidity 1.4 0.7- 2.7 0.24 1.2 0.6- 2.7 0.52 Metastatic disease 1.2 0.7- 2.1 0.43 1.3 0.7- 2.5 0.36 Anemia 1.3 0.7- 2.1 0.29 1.2 0.6- 2.2 0.47 Low albumin level 1.2 0.6- 2.1 0.49 1.1 0.5- 2.2 0.71
PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR
Authors: Albert Claude, Alexandre Rothen
Journal: The Journal of Experimental Medicine (1940)

1. The tumor-producing fraction, isolated from Chicken Tumor I by means of differential centrifugation at high speed, has been investigated as regards its power to absorb ultraviolet light. A characteristic absorption spectrum was found, with a maximum at λ2575. The absorbing power of the material in that region was largely due to the presence of nucleic acid, or of a closely related compound. 2. Inactivation of the purified tumor fraction with ultraviolet light depressed the absorbing power of the material, especially in the region of 2600–2500Å. These changes were those which nucleic acid would present under the same conditions. 3. Inactivation of the tumor agent with acid or alkali was accompanied by decomposition of the tumor nucleoprotein and passage of free nucleic acid into solution. 4. Partial or complete inactivation of the tumor agent by heat, at 50° or 65deg;C., was attended by liberation of nucleic acid of low molecular weight. 5. The parallelism between tumor-producing activity and the integrity of the tumor ribonucleoprotein suggests that the nucleoprotein may be an essential part of the active principle.
AASLD Abstracts 1353-1605
Journal: Hepatology (2008)

Background and aims: NF-κB is an important regulator of cell proliferation and survival.NF-κB consists of five subunits (p50, p52, p65 (RelA), RelB and c-Rel) and increasing evidence suggests that they have individual functions in normal and diseased livers.The aim of this study was to investigate the role of the c-Rel subunit of NF-κB in liver disease.We found evidence that c-Rel is critically involved in hepatocyte proliferation.Methods: Mice hepatocytes were isolated with a pronase perfusion of the livers and a low-speed centrifugation.[3H]Thymidine incorporation was measured 72 hr after hepatocytes were isolated.In addition, FACS cell cycle analysis by propidium iodide staining was performed on freshly isolated hepatocytes.The role of c-Rel in proliferation in vivo was studied during recovery from chronic carbon tetrachloride (CCl4)-induced liver injury and partial hepatectomy and livers were stained for different markers of proliferation (BrdU, PCNA and mitotic bodies).The expression of growth regulating genes was studied with Taq-Man Low Density Array (TLDA) and real-time PCR.Results: Incorporation of [3H]thymidine was 70% higher in wildtype than c-Rel knockout mice indicating a deficiency in basal hepatocyte proliferation.Flow cytometry of propidium iodide-stained nuclei demonstrated a significant difference in DNA content between wildtype and c-Rel knockout indicative of a cell cycle arrest in G1.During recovery from chronic CCl4-induced liver injury, staining for PCNA and mitotic bodies revealed significant lower levels of hepatocyte proliferation in c-Rel knockout mice.These mice also showed lower hepatocyte proliferation levels at 72 hrs after partial hepatectomy in BrdU and PCNA-stained sections (14-and 4-fold lower, successively).Transcript levels of FoxM1b associated with hepatocyte regeneration were significantly lower in c-Rel knockout mice.Conclusion: Our finding reveals that c-Rel is an important factor in control of hepatocyte proliferation in the liver following injury and regeneration.This novel function of c-Rel makes it a potential therapeutic target to stimulate hepatocyte regeneration in patients with liver fibrosis.Increasing c-Rel in livers of hepatectomy patients could enhance the liver regeneration in the remnant liver.
Real-Time Monitoring of Vaccination Campaign Performance Using Mobile Phones — Nepal, 2016
Authors: David H. Oh, Alya Dabbagh, James L. Goodson, Peter M. Strebel, Sanjita Thapa, Jagat Narain Giri, Sagar Ratna Shakya, Sudhir Khanal
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In 2012, the Global Vaccine Action Plan* established a goal to achieve measles and rubella elimination in five of the six World Health Organization (WHO) regions (194 countries) by 2020 (1). Measles elimination strategies aim to achieve ≥95% coverage with 2 routine doses of measles-containing vaccine (2), and implement supplementary immunization activities (SIAs)† in settings where routine coverage is low or where there are subpopulations at high risk. To ensure SIA quality and to achieve ≥95% SIA coverage nationally, rapid convenience monitoring (RCM) is used during or immediately after SIAs (3,4). The objective of RCM is to find unvaccinated children and to identify reasons for nonvaccination in areas with persons at high risk, to enable immediate implementation of corrective actions (e.g., reassigning teams to poorly vaccinated areas, modifying the timing of vaccination, or conducting mop-up vaccination activities). This report describes pilot testing of RCM using mobile phones (RCM-MP) during the second phase of an SIA in Nepal in 2016. Use of RCM-MP resulted in 87% timeliness and 94% completeness of data reporting and found that, although 95% of children were vaccinated, 42% of areas required corrective vaccination activities. RCM-MP challenges included connecting to mobile networks, small phone screen size, and capturing Global Positioning System (GPS) coordinates. Nonetheless, use of RCM-MP led to faster data transmission, analysis, and decision-making and to increased accountability among levels of the health system.