bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Novel Prostate-Specific Membrane Antigen-Targeted Near-Infrared Imaging Agent for Fluorescence-Guided Surgery of Prostate Cancer
Authors: Kularatne Sumith A. , Thomas Mini , Myers Carrie H. , Gagare Pravin , Kanduluru Ananda K. , Crian Christa J. , Cichocki Brandy N. 
Published: September 2018

Abstract

Purpose:
The ability to locate and remove all malignant lesions during radical prostatectomy leads not only to prevent biochemical recurrence (BCR) and possible side effects but also to improve the life expectancy of patients with prostate cancer. Fluorescence-guided surgery (FGS) has emerged as a technique that uses fluorescence to highlight cancerous cells and guide surgeons to resect tumors in real time. Thus, development of tumor-specific near-infrared (NIR) agents that target biomarkers solely expressed on prostate cancer cells will enable to assess negative tumor margins and affected lymph nodes.

Experimental Design:
Because PSMA is overexpressed in prostate cancer cells in &gt;90% of the prostate cancer patient population, a prostate-specific membrane antigen (PSMA)-targeted NIR agent (OTL78) was designed and synthesized. Optical properties, in vitro and in vivo specificity, tumor-to-background ratio (TBR), accomplishment of negative surgical tumor margins using FGS, pharmacokinetics (PKs) properties, and preclinical toxicology of OTL78 were then evaluated in requisite models.

Results:
OTL78 binds to PSMA-expressing cells with high affinity, concentrates selectively to PSMA-positive cancer tissues, and clears rapidly from healthy tissues with a half-time of 17 minutes. It also exhibits an excellent TBR (5:1) as well as safety profile in animals.

Conclusions:
OTL78 is an excellent tumor-specific NIR agent for use in fluorescence-guided radical prostatectomy and FGS of other cancers.
A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies
Authors: Rasco Drew W. , Papadopoulos Kyriakos P. , Pourdehnad Michael , Gandhi Anita K. , Hagner Patrick R. , Li Yan , Wei Xin , Chopra Rajesh , Hege Kristen , DiMartino Jorge , Shih Kent 
Published: September 2018

Abstract

Purpose:
Avadomide is a novel, small-molecule therapeutic agent that modulates cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory activities. This first-in-human phase I study (NCT01421524) evaluated the safety and clinical activity of avadomide in patients with advanced solid tumors, non-Hodgkin lymphoma (NHL), and multiple myeloma.

Patients and Methods:
Thirty-four patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3 design (0.5–3.5 mg, 28-day continuous dosing cycles). The primary objectives were to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of avadomide. The secondary objective was to determine preliminary avadomide efficacy. Exploratory objectives included evaluation of pharmacodynamic effects of avadomide.

Results:
DLTs were reported in 2 patients, and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common TEAEs (≥15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5 and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response, and 2 had partial responses. Although no objective responses were observed in patients with solid tumors, 5 of 6 patients with brain cancer experienced nonprogression of ≥6 months. A dose-dependent relationship between Aiolos degradation in peripheral B and T cells occurred within 5 hours of the first dose of avadomide administered, starting at 0.5 mg.

Conclusions:
Avadomide monotherapy demonstrated acceptable safety and favorable pharmacokinetics in patients with solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were observed in NHL.
Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non–Small Cell Lung Cancer
Authors: Corredor Germán , Wang Xiangxue , Zhou Yu , Lu Cheng , Fu Pingfu , Syrigos Konstantinos , Rimm David L. , Yang Michael , Romero Eduardo , Schalper Kurt A. , Velcheti Vamsidhar , Madabhushi Anant 
Published: September 2018

Abstract

Purpose:
The presence of a high degree of tumor-infiltrating lymphocytes (TIL) has been proven to be associated with outcome in patients with non–small cell lung cancer (NSCLC). However, recent evidence indicates that tissue architecture is also prognostic of disease-specific survival and recurrence. We show a set of descriptors (spatial TIL, SpaTIL) that capture density, and spatial colocalization of TILs and tumor cells across digital images that can predict likelihood of recurrence in early-stage NSCLC.

Experimental Design:
The association between recurrence in early-stage NSCLC and SpaTIL features was explored on 301 patients across four different cohorts. Cohort D1 (n = 70) was used to identify the most prognostic SpaTIL features and to train a classifier to predict the likelihood of recurrence. The classifier performance was evaluated in cohorts D2 (n = 119), D3 (n = 112), and D4 (n = 112). Two pathologists graded each sample of D1 and D2; intraobserver agreement and association between manual grading and likelihood of recurrence were analyzed.

Results:
SpaTIL was associated with likelihood of recurrence in all test sets (log-rank P &lt; 0.02). A multivariate Cox proportional hazards analysis revealed an HR of 3.08 (95% confidence interval, 2.1–4.5, P = 7.3 × 10−5). In contrast, agreement among expert pathologists using tumor grade was moderate (Kappa = 0.5), and the manual TIL grading was only prognostic for one reader in D2 (P = 8.0 × 10−3).

Conclusions:
A set of features related to density and spatial architecture of TILs was found to be associated with a likelihood of recurrence of early-stage NSCLC. This information could potentially be used for helping in treatment planning and management of early-stage NSCLC.
See related commentary by Peled et al., p. 1449
Padrão Sazonal da Precipitação e Circulação na América do Sul Associado à Oscilação Decadal do Pacífico no Período 1970-2003
Authors: Lima Bruna Simões , Silva Carlos Batista da , Silva Maria Elisa Siqueira 
Published: September 2018

Vários estudos apontam que os padrões da temperatura da superfície do mar sobre os oceanos Pacífico e Atlântico contribuem para modular os padrões atmosféricos da América do Sul. As perturbações associadas à Oscilação Decadal do Pacífico, ODP, atingem toda a bacia oceânica e têm o potencial de impactar o clima de várias partes do globo. O presente estudo tem como objetivo caracterizar os padrões sazonais de circulação e precipitação sobre a América do Sul durante as fases negativa e positiva da ODP, entre 1970 e 2003, a partir dos dados da reanálise I do NCEP-NCAR e do Global Precipitation Climatology Center, GPCC. Durante a fase negativa da ODP, ocorre a intensificação dos alíseos sobre o nordeste da América do Sul e do escoamento de norte, na região central do continente, sendo estes processos mais intensos durante a estação chuvosa, do que na estação seca. Durante a fase positiva da ODP, ocorre o enfraquecimento dos alíseos no nordeste da América do Sul e do escoamento de norte, mas, ainda assim, o impacto climático durante a estação chuvosa é mais intenso do que na estação seca. Os dados de precipitação do GPCC indicam que durante a fase negativa da ODP ocorrem anomalias negativas de precipitação sobre o centro-leste da América do Sul e anomalias positivas sobre a região sudeste. Durante a fase positiva da ODP, o padrão de anomalias de precipitação se inverte.
Revision of Testechiniscus Kristensen, 1987 (Heterotardigrada: Echiniscidae) refutes the polar-temperate distribution of the genus
Authors: GĄSIOREK PIOTR , STEC DANIEL , ZAWIERUCHA KRZYSZTOF , KRISTENSEN REINHARDT MøBJERG , MICHALCZYK ŁUKASZ 
Published: September 2018

The family Echiniscidae comprises limno-terrestrial heterotardigrades with a strongly sclerotised dorsum, typically covered with plates. Among other members of the Echiniscus evolutionary line, the genus Testechiniscus Kristensen, 1987 stands out with well-developed ventral armature and polygonal sculpturing of the dorsal plates. It has alleged bipolar distribution (with satellite alpine records in the Holarctic). Thanks to fresh material from terra typica (Svalbard), we integratively redescribe (i.e. using light and electron microscopy imaging, morphometry, and molecular methods) the nominal species for the genus, Testechiniscus spitsbergensis (Scourfield, 1897). A comparison of the neotype series with a number of Holarctic records revealed morphological variability suggesting that the species may encompass several taxa, which, most likely, will be possible to delineate primarily with molecular tools. Moreover, based on material from Simien Mountains (Northern Ethiopia), we describe a new sibling subspecies, Testechiniscus spitsbergensis tropicalis ssp. nov. Extensive morphometric datasets are provided for the genus members for the first time. A new generic definition is proposed, embracing the two subspecies of T. spitsbergensis and T. laterculus (Schuster et al., 1980), but excluding two circum-Antarctic species, T. macronyx (Richters, 1907) and T. meridionalis (Murray, 1906). The later species are likely to be erected in the future as separate genera, and their autapomorphies are described here. In the light of our findings, the genus Testechiniscus should be recognised as a native element of the Northern Hemisphere, with mainly circum-Arctic distribution and additional, insular alpine records from the Nearctic, Palearctic and Eastern Afrotropic.
A Hierarchy of Idealized Monsoons in an Intermediate GCM
Authors: Zhou Wenyu , Xie Shang-Ping 
Published: September 2018

AbstractA hierarchy of idealized monsoons with increased degrees of complexity is built using an intermediate model with simplified physics and idealized land–sea geometry. This monsoon hierarchy helps formulate a basic understanding about the distribution of the surface equivalent potential temperatureθe, which proves to provide a general guide on the monsoon rainfall. The zonally uniform monsoon in the simplest aquaplanet simulations is explained by a linearized model of the meridional distribution ofθe, which is driven by the seasonally varying solar insolation and damped by both the monsoon overturning circulation and the local negative feedback. The heat capacities of the surface and the atmosphere give rise to an intrinsic time scale that causes the monsoon migration to lag behind the sun and reduces the monsoon extent and intensity. Monsoons with a zonally confined continent can be understood based on the zonally uniform monsoon by considering the ocean influence on the land through the westerly jet advection, which reduces the monsoon extent and induces zonal asymmetry. Monsoon responses to more realistic factors such as land geometry, albedo, and ocean heat flux are consistently predicted by their impacts on the surfaceθedistribution. The soil moisture effect, however, does not fully fit into the surfaceθeargument and provides additional control on monsoon rainfall by inducing regional circulation and rainfall patterns.
Usefulness of surgical pleth index-guided analgesia during general anesthesia: a systematic review and meta-analysis of randomized controlled trials
Authors: Won Young Ju , Lim Byung Gun , Kim Young Sung , Lee Mido , Kim Heezoo 
Published: September 2018

Objective Previous studies comparing surgical pleth index (SPI)-guided and conventional analgesia have shown differing results. Therefore, we compared the intraoperative opioid requirement, extubation time, postoperative pain scores, and perioperative adverse events between these two modalities. Methods A comprehensive literature search was conducted to identify randomized controlled trials comparing the intraoperative opioid requirement and other outcomes between the two modalities. The mean difference (MD) or the pooled risk ratio and corresponding 95% confidence interval (CI) were used for analysis. A heterogeneity (I2) assessment was performed. Results Six randomized controlled trials comparing 463 patients were included. Intraoperative opioid consumption was significantly lower in the SPI-guided than conventional analgesia group (standardized MD, −0.41; 95% CI, −0.70 to −0.11; I2 = 53%). No significant intergroup difference was observed in the pain score on the first postoperative day or the incidence of perioperative adverse events. The extubation time was considerably shorter in the SPI-guided than conventional analgesia group (MD, −1.91; 95% CI, −3.33 to −0.49; I2 = 67%). Conclusions Compared with conventional analgesia, SPI-guided analgesia can reduce intraoperative opioid consumption and facilitate extubation. Moreover, no intergroup difference was observed in the degree of postoperative pain or incidence of perioperative adverse events.
Can a linear external fixator stand as a surgical alternative to open reduction in treating a high-grade supracondylar humerus fracture?
Authors: Rinat Barak , Dujovny Eytan , Bor Noam , Rozen Nimrod , Rubin Guy 
Published: September 2018

Objective High-grade pediatric supracondylar humerus fractures are commonly treated with closed reduction and internal fixation with percutaneous pinning. When this fails, open reduction followed by internal fixation is the widely accepted procedure of choice. Use of a lateral external fixator was recently described as an optional procedure, but evidence is scarce. Methods We investigated the outcomes of upper limbs treated by either open reduction with internal fixation or closed reduction and external fixation. Results Twenty-one patients completed the long-term follow-up; 11 underwent open reduction, and 10 underwent external fixation. Most patients in both groups reported excellent satisfaction. In both groups, the modified Disabilities of the Arm, Shoulder, and Hand score was extremely low and the average elbow range of motion was almost identical. Radiographic analysis consisting of Baumann’s angle and the carrying angle revealed no statistical difference between the two groups. Discussion Optional treatment using a linear external fixator for complex nonreducible supracondylar humerus fractures yielded acceptable clinical and radiographic results, as with open reduction. Our sample size was small, but the promising results may assist in the implementation of an alternative surgical procedure, especially in more complicated cases involving flexion-type fractures or severe soft tissue damage and swelling.
A Mouse Model of Delayed Rotator Cuff Repair Results in Persistent Muscle Atrophy and Fatty Infiltration
Authors: Wang Zili , Liu Xuhui , Davies Michael R. , Horne Devante , Kim Hubert , Feeley Brian T. 
Published: September 2018

Background: Rotator cuff (RC) tears are common tendon injuries seen in orthopaedic patients. Successful repair of large and massive RC tears remains a challenge due to our limited understanding of the pathophysiological features of this injury. Clinically relevant small animal models that can be used to study the pathophysiological response to repair are limited by the lack of chronic repair models. Purpose: To develop a highly clinically relevant mouse model of delayed RC repair. Study Design: Controlled laboratory study. Methods: Three-month-old C57BL/6J mice underwent unilateral supraspinatus (SS) and infraspinatus (IS) tendon tear with immediate, 2-week delayed, or 6-week delayed tendon repair. Animals with no repair or sham surgery served as controls. Gait analysis was conducted to measure shoulder function at 2 weeks and 6 weeks after surgery. Animals were sacrificed 6 weeks after the last surgery. Shoulder joint, SS, and IS muscles were harvested and analyzed histologically. Ex vivo mechanical testing of intact and repaired SS and IS tendons was conducted. Reverse-transcriptase polymerase chain reaction was performed on SS and IS muscles to quantify atrophy, fibrosis, and fatty infiltration–related gene expression. Results: Histological and tendon mechanical testing showed that torn tendons could be successfully repaired as late as 6 weeks after transection. However, significant atrophy and fatty infiltration of muscle, with impaired shoulder function, were persistent in the 6-week delayed repair group. Shoulder function correlated with the severity of RC muscle weight loss and fatty infiltration. Conclusion: We successfully developed a clinically relevant mouse model of delayed RC repair. Six-week delayed RC repair resulted in persistent muscle atrophy and fatty infiltration with inferior shoulder function compared with acute repair. Clinical Relevance: Our novel mouse model could serve as a powerful tool to understand the pathophysiological and cellular/molecular mechanisms of RC muscle and tendon degeneration, eventually improving our strategies for treating and repairing RC tears.
No Growth Disturbance After Trochleoplasty for Recurrent Patellar Dislocation in Adolescents With Open Growth Plates
Authors: Nelitz Manfred , Dreyhaupt Jens , Williams Sean Robert March 
Published: September 2018

Background: Trochlear dysplasia is the most important risk factor for patellofemoral instability among adolescents; therefore, trochleoplasty to reshape the trochlear groove is the treatment of choice for patients with high-grade trochlear dysplasia. However, in the presence of open growth plates, there is a potential risk of injury to the distal femoral growth plate and subsequent growth disturbance. As such, most authors do not recommend trochleoplasty for skeletally immature patients. The effect of trochleoplasty on femoral growth when performed before closure of the distal femoral physis remains unclear. Hypothesis: For patients with open growth plates and an expected growth <2 years, trochleoplasty does not cause growth disturbance of the distal femur. Study Design: Case series; Level of evidence, 4. Methods: Eighteen consecutive adolescents (18 knees) with open physes and severe trochlear dysplasia underwent thin flap trochleoplasty. Pre- and postoperative radiographic examination included anteroposterior and lateral views to assess leg axis and patella alta. A preoperative radiograph of the left hand was performed to measure skeletal age. Magnetic resonance imaging was performed to evaluate trochlear dysplasia and tibial tubercle–trochlear groove distance. Evaluation included pre- and postoperative physical examination with evaluation of leg length and leg axis, Kujala score, and Tegner activity score. Results: The median age at the time of operation was 12.6 years (range, 12.2-13.3 years) for girls and 14.5 years (14.0-15.4 years) for boys. The mean follow-up after operation was 2.3 years after surgery (range, 2.0-3.0 years). At follow-up for all patients, the growth plates of the knee were closed. Impairment of growth of the distal femur was found neither clinically nor radiographically. No recurrent dislocation occurred. The median Kujala score improved significantly from 67 (range, 54-75) preoperatively to 89.5 (range, 78-96) at follow-up ( P < .01). The median visual analog scale showed significant pre- to postoperative improvement from 5 (range, 3-7) to 1 (range, 0-3) ( P < .01). The activity level according to the Tegner activity score did not change significantly. Conclusion: In this study, trochleoplasty as a treatment for patellofemoral instability of patients with open physes and an expected growth of not more than 2 years showed good clinical results without redislocation and with no growth disturbance. Therefore, for selected adolescent patients with high-grade trochlear dysplasia, trochleoplasty can be safely performed up to 2 years before the projected end of growth.
Graft Choice and the Incidence of Osteoarthritis After Anterior Cruciate Ligament Reconstruction: A Causal Analysis From a Cohort of 541 Patients
Authors: Lecoq Flore-Anne , Parienti Jean-Jacques , Murison James , Ruiz Nicolas , Bouacida Khaled , Besse Jérémy , Morin Vincent , Padiolleau Giovany , Cucurulo Thomas , Graveleau Nicolas , Hulet Christophe ,   Société Française de Chirurgie Orthopédique et de Traumatologie (SoFCOT)
Published: September 2018

Background: Anterior cruciate ligament (ACL) reconstruction is important to prevent knee osteoarthritis. Neither of the 2 most common graft techniques—the patellar tendon (PT) or hamstring tendon (HS) graft—has demonstrated superiority in terms of the long-term osteoarthritis rate. Hypothesis: Based on the International Knee Documentation Committee (IKDC) radiographic grading system, PT grafts decrease the incidence of osteoarthritis by providing better knee stability as compared with HS grafts over 12 years of follow-up. Study Design: Cohort study; Level of evidence, 3. Methods: All adults with a first ACL rupture who underwent surgery with a PT or HS graft technique between January 2002 and December 2003 were included in the 2014 French Society of Orthopedic Surgery and Traumatology Symposium database. Baseline characteristics were collected. The primary endpoint was the occurrence of moderate to severe osteoarthritis in each group. The secondary endpoints included clinical subjective evaluations by the IKDC score and Knee injury and Osteoarthritis Outcome Score. To control the differences in baseline characteristics, the data were analyzed with propensity score matching. Results: In the cohort, 541 patients from 18 centers were included: 311 PT and 230 HS ACL reconstructions. The baseline characteristics were similar after inverse probability weighting treatment (IPWT). The occurrence of osteoarthritis was similar after IPWT (19.3% for PT and 19.6% for HS, P = .94). Age at surgery >29 years and IKDC osteoarthritis stage B at the index surgery were identified as risk factors for moderate to severe osteoarthritis. Most functional outcomes were significantly higher in the HS group; however, the difference between groups remained <10 points. Of the 106 patients who needed a medial meniscectomy, the proportion of patients with moderate to severe osteoarthritis was much higher in the HS group (43.5% vs 18.3%, P = .006). However, after IPWT, the difference was not statistically significant. Conclusion: At 12 years of follow-up, neither graft technique was superior to the other in terms of the rate of osteoarthritis.
Bioelectricity production from fermentable household waste in a dual-chamber microbial fuel cell
Authors: Chatzikonstantinou D , Tremouli A , Papadopoulou K , Kanellos G , Lampropoulos I , Lyberatos G 
Published: September 2018

In this study, the use of a dual-chamber microbial fuel cell for the production of bioelectricity from a food residue biomass (FORBI) product was investigated. Food residue biomass was produced by drying and shredding the pre-sorted fermentable fraction of household food waste collected door-to-door in the Municipality of Halandri, Athens, Greece. Different organic loads of food residue biomass expressed as chemical oxygen demand (COD) were examined (0.7, 0.9, 1.4, 2.8, 6 and 14 g COD L−1, respectively). It was observed that an increase of the initial concentration of the final extract resulted in a corresponding increase in the operating time. The microbial fuel cell potential increased from 33.3 mV to 46 mV as the concentration was increased from 0.7 to 14 g COD L−1. The best performance in terms of maximum power density (29.6 mW m−2) corresponding to a current density of 88 mA m−2 was observed for 6 g COD L−1. Setting the external resistance at its optimal value (Rext = 2 kΩ) as determined by polarisation experiments, Pyield drastically increased to 13.7 and 17.3 Joule (g FORBI)−1 in two consecutive cycles. The results demonstrate that readily biodegradable substrates, such as food residue biomass, can be effectively used for enhanced bioelectricity harvesting in a microbial fuel cell.