bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-053: Towards new cryptophycins as promising payloads for ADC
Authors: Brun Marie-Priscille , Bouchard Hervé , Clerc François , Zhang Jidong , Abecassis Pierre-Yves , Amara Céline , Beys Eric , Efremenko Florence , Nicolazzi Céline , Pascual Marie-Hélène , Pasquier Olivier , Krick Alain , Berne Pierre-François , Gauzy Laurence , Karst Nathalie , Huille Sylvain , Henry Christophe , Lefebvre Anne-Marie , Sassoon Ingrid 
Published: July 2016

Abstract
Cryptophycins are a class of macrocyclic depsipeptides produced as secondary metabolites by cyanobacteria of the genus Nostoc and were found to bind to microtubules at the vinca site. The natural product C-1 isolated in 1990 and the synthetic derivative C-52 displayed potent in vitro and in vivo antitumor activity in preclinical models. Cryptophycin C-52 (LY355703) produced marginal antitumor activity at MTD in two phase II lung cancer trials and was therefore discontinued.
Considering its higher potency versus other tubulin binders such as maytansine and auristatin, this chemical series was selected for an ADC approach. Several conjugates were evaluated in vitro and in vivo based on the conjugation of C52 derivatized at the para-benzylic position of the macrocycle. As described in this study, this optimization led to the discovery of cryptophycin ADC which displayed potent antitumor activity in vivo. However, these conjugates were found unstable in mice plasma while being stable in the plasma of non-rodent species. This species-dependent instability was shown to be the result of a mice plasmatic metabolization of C52 macrocycle once conjugated to the antibody. We therefore designed and synthesized new cryptophycin ADC which exhibited improved plasmatic stability when tested in mice and enhanced therapeutic index in comparison with C52 ADC.
In conclusion, these data demonstrated the potent in vitro and in vivo antitumor activity of these new cryptophycin ADC and warrant further development of this cytotoxic payload for an ADC approach.
Citation Format: Marie-Priscille Brun, Hervé Bouchard, François Clerc, Jidong Zhang, Pierre-Yves Abecassis, Céline Amara, Eric Beys, Florence Efremenko, Céline Nicolazzi, Marie-Hélène Pascual, Olivier Pasquier, Alain Krick, Pierre-François Berne, Laurence Gauzy, Nathalie Karst, Sylvain Huille, Christophe Henry, Anne-Marie Lefebvre, Ingrid Sassoon. Towards new cryptophycins as promising payloads for ADC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-053.
Abstract LB-264: Landscape of tumor-infiltrating T-cell repertoire of human cancers
Authors: Li Bo , Liu Taiwen , Wang Binbin , Wang Jinzeng , Shukla Sachet , Dou Ruoxu , Hodi Stephen , Wu Catherine , Hacohen Nir , Liu Jun , Liu X. Shirley 
Published: July 2016

Abstract
T cells play a critical role in antitumor immunity and are the primary targets in many immunotherapies. However, the study of tumor-infiltrating T cells has been complicated by the extremely diverse repertoire of T cell receptors, characterized by the complementarity determining region 3 (CDR3). Here using our newly developed algorithm, we studied the CDR3 sequences of tumor infiltrating T cells in 9,142 RNA-seq samples across 29 diseases. In total, we assembled over 600 thousands CDR3 sequences, covering the α, β, γ, δ chains. TRBV genes usage, CDR3 sequence length and conservation of infiltrating T cells resembled those in the peripheral blood of healthy donors in many tumors, except brain and kidney cancers. About 20% of the CDR3 calls were shared in multiple individuals. T cell clonotypes carrying these CDR3 sequences are known as the ‘public T cells’. In this work, we found that public T cell CDR3 amino acid (AA) sequences are shorter compared to the private ones and the middle 3 positions of the private CDR3 sequences were enriched for hydrophobic AAs. This finding potentially suggests that private T cell clonotypes in the tumors have greater potential to recognize neoantigens. We defined clonotype per kilo-reads (CPK) to measure the diversity of T cell repertoire and identified a strong positive association between CPK and tumor mutation load, implying that neoantigens may diversify the infiltrating T cell population. In addition, we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers based on their strong associations with CPK. Finally, we identified 3 potential immunogenic somatic mutations based on their co-occurrence with CDR3 sequences. One of them, PRAMEF4 F300V, was predicted to bind strongly to both MHC-I and MHC-II, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigen and the tumor-reactive T-cell clonotype.
Citation Format: Bo Li, Taiwen Liu, Binbin Wang, Jinzeng Wang, Sachet Shukla, Ruoxu Dou, Stephen Hodi, Catherine Wu, Nir Hacohen, Jun Liu, X. Shirley Liu. Landscape of tumor-infiltrating T-cell repertoire of human cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-264.
An assessment of human-elephant conflict and associated ecological and demographic factors in Nilambur, Western Ghats of Kerala, southern India
Authors: Rohini C. K. , Aravindan T. , Vinayan P. A. , Ashokkumar M. , Das K.S. Anoop 
Published: July 2016

Elephant conservation carries cost in the form of human-elephant conflict and affects the wellbeing of people living near ecologically important areas. Conflicts impart serious challenges towards the survival of Asian Elephants, which are categorized as Endangered in the IUCN Red List of Threatened Species. Issues of wildlife conservation are least addressed in areas with less restricted categories of protection. Hence an attempt was made to evaluate the intensity of elephant conflict and factors associated with its occurrence in villages with forest fringes of North and South Forest Divisions of Nilambur, Kerala, southern India. It was hypothesized that variables such as number of houses, area of village, livestock population, forest frontage, and presence of water source along the forest boundary abutting the village to be the underlying correlates of conflict. Field studies were conducted fortnightly from June 2014 to May 2015, by visiting farms and households of 17 selected forest fringe villages. Observational methods, questionnaire surveys and secondary data collection were employed for this purpose. A total of 277 incidents of crop depredation, 12 incidents of property damage, three human injuries, and one human death due to conflict were recorded during this period. Crop raiding was highest during post monsoon season and it was low during pre-monsoon and monsoon seasons. Multiple linear regression results suggest that forest frontage and livestock population were significant predictors of conflict incidence. Information regarding the prime causes of conflict will be helpful for planning strategies for the establishment of appropriate mitigation methods. The present study serves as baseline information which will be helpful for formulating prospective management plans.
Noteworthy additions to the flora of Uttarakhand, western Himalaya, India
Authors: Rai Ishwari D. , Singh Gajendra , Rawat Gopal S. 
Published: July 2016

During recent botanical explorations, we recorded three interesting plant species from the alpine regions (>3500m) of the Uttarakhand State in the western Himalaya. After a detailed scrutiny of the literature and herbarium specimens, we ascertain their identity and report them as additions to the flora of Uttarakhand. In this paper descriptions of these species along with their phenology, distribution, photographs, ecology and phytogeographical notes have been presented.
A century later: Tricolored Pied Flat Coladenia indrani uposathra Fruhstorfer, 1911 (Hesperiidae: Pyrginae) and Crenulate Oakblue Apporasa atkinsoni Hewitson, 1869 (Lycaenidae: Theclinae) reported from Manipur, India
Authors: Soibam Baleshwor Singh , Huidrom Hermenn , Irungbam Jatishwor Singh 
Published: July 2016

The present paper reports the rediscovery of the Tricolored Pied Flat Coladenia indrani uposathra Fruhstorfer, 1911 and Crenulated Oakblue Apporasa atkinsoni Hewitson, 1869 after about 99 years after they were sighted by Tytler (1915) in Irang river and Sebong of Manipur, North East India. C. i. uposathra was sighted a Keibul Lamjao National Park (KLNP) and Heibok hills of Imphal valley on 4th and 16th May 2014 and A. atkinsoni was sighted Munnom village at Yaingangpokpi Lokchao Wildlife Sanctuary (YLWS) on 8th December 2015. A. atkinsoni is protected under schedule II of Indian (Wildlife) Protection Act 1972. The rediscovery of such very rare species in Manipur shows that more survey is needed in hills and valley regions of Manipur to know the butterfly fauna of the region.
First record of Speculitermes chadaensis Chatterjee & Thapa, 1964 (Isoptera: Termitidae) from the Western Ghats, India
Authors: Amina Poovoli , Rajmohana K. , Bhavana K. V. 
Published: July 2016

Speculitermes chadaensis Chatterjee & Thapa, 1964, a termite species under Termitidae family is reported for the first time from the Western Ghats. A distribution map of the species is also provided.
Experience With the Wearable Cardioverter-Defibrillator in Patients at High Risk for Sudden Cardiac Death
Authors: Wäßnig Nadine K. , Günther Michael , Quick Silvio , Pfluecke Christian , Rottstädt Fabian , Szymkiewicz Steven J. , Ringquist Steven , Strasser Ruth H. , Speiser Uwe 
Published: July 2016

Background:
This study evaluated the wearable cardioverter-defibrillator (WCD) for use and effectiveness in preventing sudden death caused by ventricular tachyarrhythmia or fibrillation.

Methods:
From April 2010 through October 2013, 6043 German WCD patients (median age, 57 years; male, 78.5%) were recruited from 404 German centers. Deidentified German patient data were used for a retrospective, nonrandomized analysis.

Results:
Ninety-four patients (1.6%) were treated by the WCD in response to ventricular tachyarrhythmia/fibrillation. The incidence rate was 8.4 (95% confidence interval, 6.8–10.2) per 100 patient-years. Patients with implantable cardioverter-defibrillator explantation had an incidence rate of 19.3 (95% confidence interval, 12.2–29.0) per 100 patient-years. In contrast, an incidence rate of 8.2 (95% confidence interval, 6.4–10.3) was observed in the remaining cardiac diagnosis groups, including dilated cardiomyopathy, myocarditis, and ischemic and nonischemic cardiomyopathies. Among 120 shocked patients, 112 (93%) survived 24 hours after treatment, whereas asystole was observed in 2 patients (0.03%) with 1 resulting death.

ConclusionS:
This large cohort represents the first nationwide evaluation of WCD use in patients outside the US healthcare system and confirms the overall value of the WCD in German treatment pathways.
Precipitation Effects on Motor Vehicle Crashes Vary by Space, Time, and Environmental Conditions
Authors: Tamerius J. D. , Zhou X. , Mantilla R. , Greenfield-Huitt T. 
Published: July 2016

Abstract
Numerous studies have shown that precipitation has a significant impact on motor vehicle crashes. Hourly weather radar data with a 4-km resolution and over 600 000 crashes from 2002 to 2012 in Iowa are used to assess the effects of precipitation on motor vehicle crashes. Using a matched pairs analysis, this study finds that the relative accident risk (RAR) across the state during the study period was 1.69 [1.66, 1.71]. However, RAR increased to as high as 3.7 [3.6, 4.0] and as low as 1.1 [1.0, 1.2] for frozen and liquid precipitation types, respectively. RAR also varied significantly by hour of the day, with RAR near 2 in the late afternoon and 1.3 during the early morning hours, suggesting an interaction effect between precipitation and traffic volume and/or density on crash risk. The study also shows that interstates and major highways tend to have higher RAR than smaller roads, and it was able to identify locations that are particularly sensitive to precipitation with regard to crashes. This study can be used to inform future studies on the effects of weather and climate change on crashes.
Minimal Margin Extracapsular Dissection
Authors: McMullen Caitlin P. , Smith Richard V. , Ow Thomas J. , Tassler Andrew , Schiff Bradley A. 
Published: July 2016

Objective: Extracapsular dissection (ECD) has become an accepted, less invasive alternative for the removal of select benign parotid lesions that may reduce complications. Minimal margin extracapsular dissection (MECD) with dissection on or closer to the tumor capsule may be a reasonable alternative to ECD. The objective of this study is to review the complications and safety of the MECD technique at a single institution. Subjects and Methods: Medical records for patients who underwent MECD for suspected benign parotid lesions were reviewed. Outcome measurements included intraoperative findings, complications, and recurrences. Results: Forty patients underwent a MECD for suspected benign parotid lesions. The average tumor size was 2.2 cm. Frozen section revealed low-intermediate grade mucoepidermoid carcinoma in 2 (5%) cases, requiring completion of a superficial parotidectomy at the same setting. There was 1 case of temporary facial nerve weakness and no cases of Frey syndrome. No tumor recurrences were observed within the follow-up period (average 3.5 years.) Conclusion: In the hands of an experienced surgeon, MECD may be a viable alternative to formal superficial parotidectomy. This study reports low rates of nerve weakness and Frey syndrome. Long-term follow-up is necessary to determine the ultimate risk of recurrence.
Regional Variation in the Mechanical and Microstructural Properties of the Human Anterior Cruciate Ligament
Authors: Skelley Nathan W. , Castile Ryan M. , Cannon Paul C. , Weber Christian I. , Brophy Robert H. , Lake Spencer P. 
Published: July 2016

Background: The anteromedial (AM) bundle of the anterior cruciate ligament (ACL) has a higher modulus and failure stress than does the posterolateral (PL) bundle. However, it is unknown how these properties vary within each bundle. Purpose: To quantify mechanical and microstructural properties of samples within ACL bundles to elucidate any regional variation across the ligament. We hypothesized that there are no differences within each bundle in contrast to cross-bundle variation. Study Design: Descriptive laboratory study. Methods: Sixteen human ACLs were dissected into AM and PL bundles. Three samples were taken from each bundle in an ordered sequence from AM (region 1 AM bundle) to PL (region 6 PL bundle). Each sample was tested in uniaxial tension, using quantitative polarized light imaging (QPLI) to quantify collagen fiber alignment. After preconditioning, samples were subjected to a stress-relaxation (SR) test followed by quasistatic ramp-to-failure (RF). Peak and equilibrium stress values were computed from the SR test and modulus quantified in the toe- and linear-regions of the RF. QPLI values describing collagen orientation (angle of polarization [AoP]) and strength of alignment (degree of linear polarization [DoLP]) were computed for the SR test and at points corresponding to the zero, transition point, and linear region of the RF. Results: Toe- and linear-region modulus values decreased from region 1 to 6. Slopes of regression lines increased for the average DoLP during RF, with significance at higher strains. The standard deviation of AoP values decreased during RF, indicating tighter distribution of orientation angles, with significant correlations at all points of the RF. During SR, stress values uniformly decreased but did not show significant linear regression by region. DoLP and AoP values changed slightly during SR and demonstrated significant linear variation by region at both peak and equilibrium points. Conclusion: Most microstructural and material properties evaluated in this study appear to follow a linear gradient across the ACL, rather than varying by bundle. Clinical Relevance: This AM-to-PL variation provides a more accurate description of functional tissue anatomy and can be used to assess and guide techniques of ACL reconstruction.
Human Factors and Health-Care Professionals Collaboration to Reduce Alarm Fatigue in ICU Settings at a Large Academic Medical Center
Authors: Mayer Celeste , Mauney Jennifer , Barnes Janey , Addison Ashley , Dicus Andrea K. , Hanlin Ryan , Hsieh Kelsy B. , Soares Sharmila , White Brittany L. 
Published: July 2016

Key stakeholders across healthcare’s complex socio-technical environment have been called by the Joint Commission to take part in the shared responsibility to improve alarm safety. This project demonstrated the value added from applying Human Factors principles to a process supporting the safety of patients and the work of health-care providers by reducing the non-actionable alarms in 4 in-patient care units. An Alarm Safety Quality Improvement project is described with specific objectives, methods and results. Results from this project demonstrated an iterative process which provided data and empowerment to the team. The data provided the unit leaders new actionable information and targeted intervention planning with associated meaningful measurements. The process has empowered units to tackle alarm fatigue with the necessary knowledge, tools, and support. The four in-patient care units that have completed this process saw a combined average weekly decrease of 14,000 alarms.
Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut
Authors: Kakihana Kazuhiko , Fujioka Yuki , Suda Wataru , Najima Yuho , Kuwata Go , Sasajima Satoshi , Mimura Iyo , Morita Hidetoshi , Sugiyama Daisuke , Nishikawa Hiroyoshi , Hattori Masahira , Hino Yutaro , Ikegawa Shuntaro , Yamamoto Keita , Toya Takashi , Doki Noriko , Koizumi Koichi , Honda Kenya , Ohashi Kazuteru 
Published: July 2016

Key Points
FMT was safely performed in SCT patients, with 3 complete responses and 1 partial response. Temporal microbiota dynamics seem linked to gut condition and effector regulatory T cells also increased during response to FMT.
Superior absorption and retention properties of foam-film silver dressing versus other commercially available silver dressing
Authors: Lee Seung Moon , Park Il Kyu , Kim Yong Soo , Kim Hyun Jung , Moon Hanlim , Mueller Stefan , Arumugam Harsha , Jeong Young-IL 
Published: July 2016

Abstract

Background
The aim of this study is to investigate the physicochemical and structural properties of Medifoam®Silver and to compare with other commercially available silver-containing polyurethane (PU) foam dressing in vitro.

Methods
Surface and cross-section of four polyurethane foam dressings were assessed with field-emission scanning electron microscope. Thickness, density, tensile strength, elongation, absorption rate, absorption/retention capacity and water-vapor transmission (WVT) were measured to compare physical properties of various dressing materials.

Results
Among four tested dressings, Medifoam®Silver has relatively uniform and smallest pore size in both surface and cross-section. In comparison of absorption properties with other dressing materials, Medifoam®Silver has rapid absorption rate, good absorption/retention capacity and good WVT value.

Conclusions
The data further suggests that Medifoam®Silver is a promising candidate for wound healing management.
Obesity As a Risk Factor for Anthracyclines and Trastuzumab Cardiotoxicity in Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Guenancia Charles , Lefebvre Annick , Cardinale Daniela , Yu Anthony F. , Ladoire Sylvain , Ghiringhelli François , Zeller Marianne , Rochette Luc , Cottin Yves , Vergely Catherine 
Published: July 2016

PurposePatients with metabolic syndrome have a greater risk of cardiovascular disease, although their susceptibility to chemotherapy-induced cardiac disease is not well documented. The aim of this meta-analysis was to assess associations between obesity or being overweight and cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab in patients with breast cancer.MethodsWe performed a random-effects analysis and a network meta-analysis and assessed publication bias. We included 15 studies and 8,745 patients with breast cancers who were treated with anthracyclines and sequential anthracyclines and trastuzumab.ResultsCombination of obesity and being overweight was significantly associated with a greater risk of developing cardiotoxicity after anthracyclines and a sequential anthracyclines and trastuzumab regimen in patients with breast cancer. Pooled odds ratio for cardiotoxicity was 1.38 (95% CI, 1.06 to 1.80; I2= 43%; N = 8,745) for overweight or obesity (body mass index > 25 kg/m2), 1.47 (95% CI, 0.95 to 2.28; I2= 47%; n = 2,615) for obesity, and 1.15 (95% CI, 0.83 to 1.58; I2= 27%; n = 2,708) for overweight. Associations were independent of study design, year of publication, drug regimen (anthracyclines alone v sequential anthracyclines and trastuzumab), or definitions of cardiotoxicity and of overweight or obesity. There was no evidence of publication bias; however, we could not separate the contributions of obesity-related cardiovascular risk factors, such as diabetes and hypertension, from that of obesity itself in this largely unadjusted analysis.ConclusionOur findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from anthracyclines and sequential anthracyclines and trastuzumab.
Patient Navigation in Breast Cancer Treatment and Survivorship: A Systematic Review
Authors: Baik Sharon H. , Gallo Linda C. , Wells Kristen J. 
Published: July 2016

PurposePatient navigation is an intervention approach that improves cancer outcomes by reducing barriers and facilitating timely access to cancer care. Little is known about the benefits of patient navigation during breast cancer treatment and survivorship. This systematic review evaluates the efficacy of patient navigation in improving treatment and survivorship outcomes in women with breast cancer.MethodsThe review included experimental and quasi-experimental studies of patient navigation programs that target breast cancer treatment and breast cancer survivorship. Articles were systematically obtained through electronic database searches of PubMed/MEDLINE, PsycINFO, Web of Science, CINAHL, and Cochrane Library. The Effective Public Health Practice Project Quality Assessment Tool was used to evaluate the methodologic quality of individual studies.ResultsThirteen studies met the inclusion criteria. Most were of moderate to high quality. Outcomes targeted included timeliness of treatment initiation, adherence to cancer treatment, and adherence to post-treatment surveillance mammography. Heterogeneity of outcome assessments precluded a meta-analysis. Overall, results demonstrated that patient navigation increases surveillance mammography rates, but only minimal evidence was found with regard to its effectiveness in improving breast cancer treatment outcomes.ConclusionThis study is the most comprehensive systematic review of patient navigation research focused on improving breast cancer treatment and survivorship. Minimal research has indicated that patient navigation may be effective for post-treatment surveillance; however, more studies are needed to draw definitive conclusions about the efficacy of patient navigation during and after cancer treatment.