bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual Assignment of Adult Diffuse Gliomas into the EM/PM Molecular Subtypes Using a TaqMan Low-Density Array
Authors: Li Jiuyi , Xue Yang , Wenger Anna , Sun Yingyu , Wang Zheng , Zhang Chuanbao , Zhang Yunqiu , Fekete Boglarka , Rydenhag Bertil , Jakola Asgeir Store , Jiang Tao , Carén Helena , Fan Xiaolong 
Published: September 2019

Abstract

Purpose:
We aimed to develop a diagnostic platform to capture the transcriptomic resemblance of individual adult diffuse gliomas of WHO grades II to IV to neural development and the genomic signature associated with glioma progression.

Experimental Design:
Based on the EM/PM classification scheme, we designed a RT-PCR–based TaqMan low-density array (TLDA) containing 44 classifier and 4 reference genes. Samples of a training dataset (GSE48865), characterized by RNA-sequencing, were utilized to optimize the TLDA design and to develop a support vector machine (SVM)-based prediction model. Complemented with Sanger sequencing for IDH1/2, and low coverage whole genome sequencing (WGS), the TLDA and SVM prediction model were tested in a validation (31 gliomas) and a test (121 gliomas) dataset.

Results:
Independent of morphologically defined subtypes and grades, gliomas can be individually assigned into the EM and PM glioma subtypes with the respective areas under ROC curves at 0.86 and 0.85 in the validation dataset. The EM gliomas showed a medium overall survival (OS) of 15.6 months, whereas the medium OS for PM gliomas was not reached (HR = 3.55; 95% confidence interval, 1.96–6.45). The EM and PM gliomas showed distinct patterns of genomic alterations, with IDH mutation and 1p19q codeletion in the PM gliomas and gain of chromosome 7/loss of chromosome 10 in the EM gliomas. Extensive chromosomal abnormalities marked the progression of PM gliomas.

Conclusions:
The integration of EM/PM subtyping, IDH sequencing, and low coverage WGS may improve the risk stratification and selection of treatment regimens for patients with glioma.
A Phase I Study of the Combination of Rituximab and Ipilimumab in Patients with Relapsed/Refractory B-Cell Lymphoma
Authors: Tuscano Joseph M. , Maverakis Emanual , Groshen Susan , Tsao-Wei Denice , Luxardi Guillaume , Merleev Alexander A. , Beaven Anne , DiPersio John F. , Popplewell Leslie , Chen Robert , Kirschbaum Mark , Schroeder Mark A. , Newman Edward M. 
Published: September 2019

Abstract

Purpose:
Based on the potential for ipilimumab (I) to augment T-cell activation, we hypothesize that ipilimumab would augment the efficacy of rituximab (R) in patients with relapsed/refractory (R/R) CD20+non-Hodgkin's lymphoma (NHL). This phase I study aimed to identify a recommended phase 2 dose, document toxicities, and preliminarily assess efficacy and potential predictive biomarkers.

Patients and Methods:
Thirty-three patients with R/R CD20+B-cell lymphoma received R at 375 mg/m2weekly for 4 weeks and I at 3 mg/kg on day 1 and every 3 weeks for four doses. Responding patients went on to maintenance with each agent given every 12 weeks. To facilitate correlative analysis, the expansion phase randomized patients to simultaneous R+I versus R with I delayed 2 weeks.

Results:
Toxicity was manageable; no dose-limiting toxicity was observed at the doses studied. When considering the entire cohort, efficacy was modest, with an objective response rate (ORR) of 24% and median progression-free survival (PFS) of 2.6 months. However, in follicular lymphoma patients, the ORR was 58% with a median PFS of 5.6 months. The randomized comparison of R with R+I demonstrated that R+I resulted in more effective B-cell depletion (BCD). Both B-cell depletion and the ratio of CD45RA−regulatory T cell (Treg) to Treg were associated with response at all time points.

Conclusions:
The combination of R+I has manageable toxicity and encouraging efficacy in R/R follicular lymphoma. The ratio of CD45RA−Tregs to total Tregs, and peripheral BCD should be studied further as potential predictors of response.
Impact of Autologous Transplantation in Patients with Multiple Myeloma with t(11;14): A Propensity-Score Matched Analysis
Authors: Saini Neeraj , Ma Junsheng , Milton Denái R. , Patel Romil , Varma Ankur , Bashir Qaiser , Delgado Ruby , Mukherjee Akash , Rondon Gabriela , Popat Uday R. , Hosing Chitra M. , Nieto Yago , Kebriaei Partow , Alousi Amin M. , Ahmed Sairah , Tang Guilin , Mehta Rohtesh , Srour Samer , Khouri Issa F. , Iyer Swaminathan , Weber Donna M. , Thomas Sheeba K. , Lee Hans C. , Manasanch Elisabet E. , Patel Krina K. , Orlowski Robert Z. , Champlin Richard E. , Qazilbash Muzaffar H. 
Published: September 2019

Abstract

Purpose:
Patients with multiple myeloma with t(11;14) have been considered to have standard-risk disease. However, several recent reports have shown contradictory results. We identified 95 patients with multiple myeloma with t(11;14) on FISH studies, who underwent upfront autologous hematopoietic stem cell transplant (auto-HCT) at our center. We compared their outcome with a group of standard-risk patients with multiple myeloma who had diploid cytogenetics by both conventional cytogenetics (CC) and FISH (n = 287).

Experimental Design:
To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis. A total of 160 patients, 80 in each group, were identified. Patients in the 2 groups were matched for age, International staging system stage at diagnosis, serum creatinine at presentation, disease status at auto-HCT, type of preparative regimens, dose of melphalan used for conditioning, and induction and maintenance regimens.

Results:
Patients in t(11;14) group had a post auto-HCT overall response rate (ORR) of 97.5% (78/80), compared with 100% (80/80) in the standard-risk control group (P = 0.50). Complete response rate in the t(11;14) group was 35% (28/80), compared with 45% (36/80) in the standard-risk control group (P = 0.26). The 4-year PFS rates were 40.8% (95% CI, 29.6%–56.1%) and 51.1% (95% CI, 39.4%–66.3%) in the t(11;14) and standard-risk control groups, respectively (P = 0.14). The 4-year OS rates were 74.9% (95% CI, 63.3%–88.7%) and 88.3% (95% CI, 80.4%–97.0%) in the t(11;14) and standard-risk control groups, respectively (P = 0.17). Also, patients with t(11;14) with concurrent cytogenetics had significantly poor PFS and OS compared with a propensity matched standard-risk control group.

Conclusions:
Our study confirms that t(11;14) multiple myeloma undergoing upfront autologous transplantation had similar outcomes as patients with multiple myeloma with normal cytogenetic and FISH studies. Existence of additional genomic aberrations by CC or FISH was associated with a worse outcome.
Combination of PPARγ Agonist Pioglitazone and Trabectedin Induce Adipocyte Differentiation to Overcome Trabectedin Resistance in Myxoid Liposarcomas
Authors: Frapolli Roberta , Bello Ezia , Ponzo Marianna , Craparotta Ilaria , Mannarino Laura , Ballabio Sara , Marchini Sergio , Carrassa Laura , Ubezio Paolo , Porcu Luca , Brich Silvia , Sanfilippo Roberta , Casali Paolo Giovanni , Gronchi Alessandro , Pilotti Silvana , D'Incalci Maurizio 
Published: September 2019

Abstract

Purpose:
This study was aimed at investigating whether the PPARγ agonist pioglitazone—given in combination with trabectedin—is able to reactivate adipocytic differentiation in myxoid liposarcoma (MLS) patient-derived xenografts, overcoming resistance to trabectedin.

Experimental Design:
The antitumor and biological effects of trabectedin, pioglitazone, and the combination of the two drugs were investigated in nude mice bearing well-characterized MLS xenografts representative of innate or acquired resistance against trabectedin. Pioglitazone and trabectedin were given by daily oral and weekly i.v. administrations, respectively. Molecular studies were performed by using microarrays approach, real-time PCR, and Western blotting.

Results:
We found that the resistance of MLS against trabectedin is associated with the lack of activation of adipogenesis. The PPARγ agonist pioglitazone reactivated adipogenesis, assessed by histologic and gene pathway analyses. Pioglitazone was well tolerated and did not increase the toxicity of trabectedin. The ability of pioglitazone to reactivate adipocytic differentiation was observed by morphologic examination, and it is consistent with the increased expression of genes such as ADIPOQ implicated in the adipogenesis process. The determination of adiponectin by Western blotting constitutes a good and reliable biomarker related to MLS adipocytic differentiation.

Conclusions:
The finding that the combination of pioglitazone and trabectedin induces terminal adipocytic differentiation of some MLSs with the complete pathologic response and cure of tumor-bearing mice provides a strong rationale to test the combination of trabectedin and pioglitazone in patients with MLS.
Differences in Genome-wide DNA Methylation Profiles in Breast Milk by Race and Lactation Duration
Authors: Davis Lynn Brittny C. , Bodelon Clara , Pfeiffer Ruth M. , Yang Hannah P. , Yang Howard H. , Lee Maxwell , Laird Peter W. , Campan Mihaela , Weisenberger Daniel J. , Murphy Jeanne , Sampson Joshua N. , Browne Eva P. , Anderton Douglas L. , Sherman Mark E. , Arcaro Kathleen F. , Gierach Gretchen L. 
Published: September 2019

Abstract
Black women in the United States are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive stage influences a woman's risk for, and potentially contributes to racial disparities in, breast cancer. Breast milk samples and demographic, behavioral, and reproductive data, were obtained from cancer-free, uniparous, and lactating U.S. black (n = 57) and white (n = 82) women, ages 19–44. Genome-wide DNA methylation analysis was performed on extracted breast milk DNA using the Infinium HumanMethylation450 BeadChip. Statistically significant associations between breast cancer risk factors and DNA methylation beta values, adjusting for potential confounders, were determined using linear regression followed by Bonferroni Correction (P &lt; 1.63 × 10−7). Epigenetic analysis in breast milk revealed statistically significant associations with race and lactation duration. Of the 284 CpG sites associated with race, 242 were hypermethylated in black women. All 227 CpG sites associated with lactation duration were hypomethylated in women who lactated longer. Ingenuity Pathway Analysis of differentially methylated promoter region CpGs by race and lactation duration revealed enrichment for networks implicated in carcinogenesis. Associations between DNA methylation and lactation duration may offer insight on its role in lowering breast cancer risk. Epigenetic associations with race may mediate social, behavioral, or other factors related to breast cancer and may provide insight into potential mechanisms underlying racial disparities in breast cancer incidence.
Cinetorhynchus gabonensis, a new species of hinge-beak shrimp (Crustacea: Decapoda: Rhynchocinetidae) from the eastern Atlantic
Authors: ĎURIŠ ZDENĚK , ŠOBÁŇOVÁ ANNA , WIRTZ PETER 
Published: September 2019

A new species of the rhynchocinetid genus Cinetorhynchus, C. gabonensis sp. n. from the Atlantic waters of Gabon, is described based on morphological and molecular comparisons and its distinctive colour pattern. This is the second known species of the genus in the eastern Atlantic, and the third species in the Atlantic as the whole. The new species is more closely related to the western Atlantic C. manningi, both having quadrispinose ambulatory dactyli (i.e. with unguis + 3 ventral spinules), but differs from the latter by the presence of an arthrobranch on the three anterior pereiopods (vs only on the first pereiopod in C. manningi). The branchial formula of the new species is consistent with most of the Indo-West Pacific congeners, and with the amphi-Atlantic C. rigens; the latter possessing trispinose ambulatory dactyli. Other distinctions of the new species from its congeners are in the carpal and meral spinulation of the ambulatory legs, and in the posterolateral and posteroventral armament of pleomeres IV and V. Cinetorhynchus gabonensis sp. n. differs from both known Atlantic congeners also by a specific colour pattern which is dense deep-red mottled with a pair of small white spots delineated by deep-red broad rings on the top of the third pleomere.
Connection between Sea Surface Anomalies and Atmospheric Quasi-Stationary Waves
Authors: Wolf G. , Czaja A. , Brayshaw D. J. , Klingaman N. P. 
Published: September 2019

AbstractLarge-scale, quasi-stationary atmospheric waves (QSWs) are known to be strongly connected with extreme events and general weather conditions. Yet, despite their importance, there is still a lack of understanding about what drives variability in QSW. This study is a step toward this goal, and it identifies three statistically significant connections between QSWs and sea surface anomalies (temperature and ice cover) by applying a maximum covariance analysis technique to reanalysis data (1979–2015). The two most dominant connections are linked to El Niño–Southern Oscillation and the North Atlantic Oscillation. They confirm the expected relationship between QSWs and anomalous surface conditions in the tropical Pacific and the North Atlantic, but they cannot be used to infer a driving mechanism or predictability from the sea surface temperature or the sea ice cover to the QSW. The third connection, in contrast, occurs between late winter to early spring Atlantic sea ice concentrations and anomalous QSW patterns in the following late summer to early autumn. This new finding offers a pathway for possible long-term predictability of late summer QSW occurrence.
Analysis of Potential Conflicts of Interest among Otolaryngologic Patient Advocacy Organizations in 2016
Authors: Kondamuri Neil S. , Rathi Vinay K. , Naunheim Matthew R. , Sethi Rosh V. , Miller Ashley L. , Varvares Mark A. 
Published: September 2019

Patient advocacy organizations (PAOs) are nonprofits dedicated to benefiting patients and their families through activities such as education/counseling and research funding. Although medical drug/device companies may serve as important partners, industry donations may bias the efforts of PAOs. We conducted a retrospective cross‐sectional analysis of the Kaiser Health News nonprofit database to identify and characterize otolaryngologic PAOs (n = 32) active in 2016. Among these PAOs, half (n = 16, 50.0%) focused on otologic diseases, and mean total annual revenue was $3.1 million. Among the 15 PAOs (46.9%) with publicly available donor lists, 10 (66.7%) received donations from industry. Few PAOs publicly reported the total amount donated by industry (n = 3, 9.4%) or published policies for mitigating potential financial conflicts of interest with donors (n = 3, 9.4%). Requiring drug and device companies to publicly report donations to PAOs may help patients, providers, and policy makers to better understand advocacy by these influential stakeholders.
Limited Open Reduction and Internal Fixation of Calcaneal Fractures
Authors: Bremer Anne K. , Kraler Lukas , Frauchiger Lars , Krause Fabian G. , Weber Martin 
Published: September 2019

Background: The treatment of displaced intra-articular calcaneal fractures remains a challenge and the optimal approach is still controversial. The main reason to avoid the extended lateral approach is the high complication rate due to wound healing problems. We report on 16 years of experience with a standardized limited open reduction and internal fixation technique. Methods: Between 2001 and 2017, we prospectively followed 240 consecutive patients operatively treated for a displaced intra-articular calcaneal fracture. Patients with open, multiple, bilateral, extra-articular, and Sanders IV fractures and those lost to follow-up were excluded. A lateral subtalar approach was used, with a cast for 8 weeks and full weightbearing allowed after 12 weeks. Follow-up examinations were scheduled until 24 months. Subjective and clinical assessment included gait abnormality, subtalar and ankle range of motion, and stability and alignment. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score was calculated. Alignment was analyzed on standard radiographs. In total, 131 patients were excluded. The remaining 109 patients were followed for a minimum of 24 months (34.4 ± 14.2 [range, 24-102] months). Results: The mean AOFAS score was 87 ± 13 (range, 32-100). “Excellent” and “good” results, as well as hindfoot motion with “normal/mild” and “moderate” restrictions, were seen in 80% of patients. Early reoperations were performed for insufficient reduction (2 patients), delayed wound healing (debridement, 3 patients), and hematoma (1 patient). Late revisions were arthrodesis (3 patients), medializing calcaneal osteotomy (1 patient), and implant removal (53 patients; 49%). Conclusion: The presented approach has remained unmodified for 16 years and resulted in consistently good functional results. The main disadvantage was the high rate of heel screw removal. Level of Evidence: Level IV, retrospective case series.
The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study
Authors: Wu Xia , Dai Min , Buch Heena , Bai Jianling , Long Wenwu , Long Chuyan , Tang Xianyan , Tu Hua , Zhang Renjie , Zhu Cairong , Yang Shaoqi , Cui Bota , Ji Guozhong , Zhang Faming 
Published: September 2019

Background: Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it. Methods: A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed. Results: A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p = 0.000 and 56.80% vs. 41.45%, p = 0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT. Conclusions: This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.
Patients’ attitudes to discontinuing not-indicated long-term antidepressant use: barriers and facilitators
Authors: Eveleigh Rhona , Speckens Anne , van Weel Chris , Oude Voshaar Richard , Lucassen Peter 
Published: September 2019

Background: Long-term antidepressant use has increased exponentially, though this is not always according to guidelines. Our previous randomized controlled trial (RCT) showed that participants using antidepressants long term without a proper indication were apprehensive to stop: only half were willing to attempt to discontinue their antidepressant use. The objective of this study was to explore participants’ barriers and facilitators for stopping long-term antidepressant use without a current proper indication. Methods: Semistructured interviews with participants from the intervention group of our RCT, a cluster-RCT in general practice in the Netherlands. The latter study was a stop trial with patients on long-term antidepressant use without a current indication (no psychiatric diagnosis). Participants of the intervention group of the RCT had been provided with advice to stop antidepressants. Participants of the current interview study were purposively sampled (from the intervention group of the RCT) to ensure diversity in age, sex, and intention to discontinue the antidepressant. Analysis was performed as an iterative process, based on the constant comparative method. Data collection proceeded until saturation was reached. Results: A total of 16 participants were interviewed. Fear (of recurrence, relapse, or to disturb the equilibrium) was the most important barrier; prior attempts fueled these anticipations. Also prominent as a barrier was the notion that antidepressants are necessary to counter a deficiency of serotonin. Facilitators were information on duration of usage given at the time of first prescription and confidence in a successful attempt. We found many participants struggling between barriers and facilitators to discontinue and participants not discontinuing while experiencing no barriers (ambivalence). Conclusion: Fear is an important motive for patients considering discontinuation of antidepressants. Serotonin deficiency as explanation for antidepressant effectiveness promotes life-long use and hinders discontinuation of antidepressant treatment. The prospect of discontinuation at first prescription can facilitate a future discontinuation attempt. General practitioners should be aware of their patients’ fears, expectations, and attributions toward antidepressant use/discontinuation, and of new developments in taper methods.
Odontogenic Cyst From an Ectopic Supernumerary Tooth Impacted in the Orbital Floor
Authors: Naus Abbie , Hernandez Stephen , Kane Anne C. , Nuss Daniel W. 
Published: September 2019

Objectives: Supernumerary dentition has been found to occur in various areas of the head and neck. Although they are commonly found along the dental arch, there are some instances of ectopic supernumerary teeth found elsewhere in the upper aero digestive tract. This case report details an impacted molar tooth in the orbital floor. Methodology: We present an unusual case of a 30-year-old male with a chief complaint of nasal obstruction. Clinically, it was manifested with an impacted molar in the orbital floor with associated bony expansion into the maxillary and ethmoid sinuses. Results: Radiographically, CT scan revealed a benign appearing expansile mass in the left maxilla, completely occupying the sinus and extending into the nose and expanding laterally into the cheek. There appeared to be a well-formed tricuspid tooth clearly visible at the top of this lesion protruding into the left orbit. The patient underwent endoscopic surgical removal, showed findings of an impacted tricuspid in the medial and inferior walls of the orbit. Histopathologic examination confirmed a large cyst lined by thick stratified squamous epithelium and embedded with dense fibrous connective tissue, consistent with an orthokeratinized odontogenic cyst. The medial orbital wall was decompressed, and his postoperative course was uneventful with no orbital complications. Ectopic supernumerary teeth are unusual findings, particularly in association with the orbit. They are frequently impacted and as such can lead to the development of cystic lesions. As with other odontogenic cysts, surgery is usually definitive. This case study demonstrates complete removal with endoscopic surgery.