bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gonadal Functioning and Perceptions of Infertility Risk Among Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study
Authors: Lehmann Vicky , Chemaitilly Wassim , Lu Lu , Green Daniel M. , Kutteh William H. , Brinkman Tara M. , Srivastava Deo Kumar , Robison Leslie L. , Hudson Melissa M. , Klosky James L. 
Published: February 2019

PURPOSE To describe perceptions of infertility risk among adult survivors of childhood cancer, to test the concordance of survivors’ risk perceptions and their adult fertility status, and to identify explanatory factors (sociodemographic factors, gonadotoxic treatments, reproductive history, sexual dysfunction) associated with these outcomes. PATIENTS AND METHODS Adult childhood cancer survivors (N = 1,067; without children or a history of pregnancies) completed questionnaires that asked about infertility risk perceptions and participated in physical evaluations, including biomarkers of gonadal functioning (eg, semen analysis, blood hormone levels, menses). Multivariable regression models tested associations between explanatory factors and risk perceptions as well as concordance of perceptions and fertility status. RESULTS Most childhood cancer survivors (61.9%) perceived themselves at increased risk for infertility, which was significantly associated with sociodemographic factors (older age, white ethnicity, being married/partnered, higher education), gonadotoxic treatments, fertility concerns, previous unsuccessful attempts to conceive, and sexual dysfunction (all P < .05). Laboratory-evaluated impaired gonadal function was found in 24.3% of female and 55.6% of male survivors, but concordance with survivors’ risk perceptions was low (Cohen’s κ < .19). Most survivors with discordant perceptions overestimated risk (ie, perceived being at risk, though fertility status seemed normal; 19.7% of male and 43.6% of female survivors), whereas a minority underestimated risk (ie, perceived no risk but were impaired/infertile; 16.3% of male and 5.3% of female survivors). Factors related to discordance included sociodemographics, gonadotoxic treatments, fertility concerns, and sexual dysfunction (all P < .05). CONCLUSION Although childfree survivors may correctly consider themselves at risk for infertility on the basis of their previous treatments, such risk perceptions were discordant from laboratory-evaluated fertility status among many survivors in adulthood. Thus, repeated fertility-related communication throughout survivorship is essential, because treatment-indicated risk does not equal fertility status after treatment. Offering fertility testing to those who were at risk and/or those with fertility-related concerns is recommended.
First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers
Authors: Sikic Branimir I. , Lakhani Nehal , Patnaik Amita , Shah Sumit A. , Chandana Sreenivasa R. , Rasco Drew , Colevas A. Dimitrios , O’Rourke Timothy , Narayanan Sujata , Papadopoulos Kyriakos , Fisher George A. , Villalobos Victor , Prohaska Susan S. , Howard Maureen , Beeram Muralidhar , Chao Mark P. , Agoram Balaji , Chen James Y. , Huang Jie , Axt Matthew , Liu Jie , Volkmer Jens-Peter , Majeti Ravindra , Weissman Irving L. , Takimoto Chris H. , Supan Dana , Wakelee Heather A. , Aoki Rhonda , Pegram Mark D. , Padda Sukhmani K. 
Published: February 2019

PURPOSE To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis. PATIENTS AND METHODS Adult patients with solid tumors were treated in four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort. RESULTS Sixty-two patients were treated: 11 in part A, 14 in B, 22 in C, and 15 in the biopsy cohort. Part A used doses that ranged from 0.1 to 3 mg/kg. On the basis of tolerability and receptor occupancy studies that showed 100% CD47 saturation on RBCs, 1 mg/kg was selected as the priming dose. In subsequent groups, patients were treated with maintenance doses that ranged from 3 to 45 mg/kg, and most toxicities were mild to moderate. These included transient anemia (57% of patients), hemagglutination on peripheral blood smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg. Two patients with ovarian/fallopian tube cancers had partial remissions for 5.2 and 9.2 months. CONCLUSION 5F9 is well tolerated using a priming dose at 1 mg/kg on day 1 followed by maintenance doses of up to 45 mg/kg weekly.
Primary CNS Lymphoma in India: A 17-Year Experience From the All India Institute of Medical Sciences
Authors: Patekar Mukesh , Adhikari Narayan , Biswas Ahitagni , Raina Vinod , Kumar Lalit , Mohanti Bidhu Kalyan , Gogia Ajay , Sharma Atul , Batra Atul , Bakhshi Sameer , Garg Ajay , Thulkar Sanjay , Sharma Meher Chand , Vishnubhatla Sreenivas , Baghmar Saphalta , Sahoo Ranjit Kumar 
Published: February 2019

PURPOSE The information about the outcome of primary CNS lymphoma (PCNSL) in India is scarce, because there is no population-based or large hospital-based data. MATERIALS AND METHODS This is a retrospective study that spanned 17 years (2001 to 2017) to study the outcome of PCNSL at the All India Institute of Medical Sciences (AIIMS), which is a tertiary care center in Northern India. RESULTS Only one of 99 patients was positive for HIV serology. Diffuse large B-cell lymphoma was the most common histology (97.7%). The median patient age was 50 years (range, 13 to 70 years), and the ratio of men to women was 1.9. The median duration of symptoms before diagnosis was 3.5 months (range, 0.5 to 48 months), and 58.5% had a performance status (PS) of 3 or more. Multiple intracranial lesions were present in 81.8% of patients. Surgical resection was performed in 45%, and approximately 22% of patients were ineligible for treatment. Most patients (n = 73) were treated with high-dose methotrexate (HDMTX)–based regimens (ie, methotrexate, vincristine, and procarbazine with or without rituximab). Pharmacokinetic monitoring of methotrexate was not available at our center. HDMTX-related mortality was 3.9%. The median follow-up duration, event-free survival (EFS), and overall survival (OS) were 34 months, 20.4 months, and 31.7 months, respectively. Addition of rituximab (n = 27) to MVP resulted in a higher objective response rate (88.9% v 73.9% without rituximab; P = .12), complete remission (81.5% v 56.5%; P = .03), 2-year EFS (57.3% v 40.4%; P = .02), and 2-year OS (61.6% v 53.4%; P = .056). CONCLUSION This is the largest study of PCNSL from India. The patients were immunocompetent and young but presented with a high-burden disease that precluded treatment in approximately 22%. The treatment with HDMTX appears safe without pharmacokinetic monitoring. The outcome is comparable to those observed in the West, and rituximab use showed additional benefit. There are notable barriers with respect to management of PCNSL in the real world, and efforts are required to improve the outcome more.
NADPH Oxidase Mediates Membrane Androgen Receptor–Induced Neurodegeneration
Authors: Tenkorang Mavis A A , Duong Phong , Cunningham Rebecca L 
Published: February 2019

AbstractOxidative stress (OS) is a common characteristic of several neurodegenerative disorders, including Parkinson disease (PD). PD is more prevalent in men than in women, indicating the possible involvement of androgens. Androgens can have either neuroprotective or neurodamaging effects, depending on the presence of OS. Specifically, in an OS environment, androgens via a membrane-associated androgen receptor (mAR) exacerbate OS-induced damage. To investigate the role of androgens on OS signaling and neurodegeneration, the effects of testosterone and androgen receptor activation on the major OS signaling cascades, the reduced form of NAD phosphate (NADPH) oxidase (NOX)1 and NOX2 and the Gαq/inositol trisphosphate receptor (InsP3R), were examined. To create an OS environment, an immortalized neuronal cell line was exposed to H2O2 prior to cell-permeable/cell-impermeable androgens. Different inhibitors were used to examine the role of G proteins, mAR, InsP3R, and NOX1/2 on OS generation and cell viability. Both testosterone and DHT/3-O-carboxymethyloxime (DHT)–BSA increased H2O2-induced OS and cell death, indicating the involvement of an mAR. Furthermore, classical AR antagonists did not block testosterone’s negative effects in an OS environment. Because there are no known antagonists specific for mARs, an AR protein degrader, ASC-J9, was used to block mAR action. ASC-J9 blocked testosterone’s negative effects. To determine OS-related signaling mediated by mAR, this study examined NOX1, NOX2, Gαq. NOX1, NOX2, and the Gαq complex with mAR. Only NOX inhibition blocked testosterone-induced cell loss and OS. No effects of blocking either Gαq or G protein activation were observed on testosterone’s negative effects. These results indicate that androgen-induced OS is via the mAR–NOX complex and not the mAR–Gαq complex.
Attenuation of Weight Loss Through Improved Antilipolytic Effect in Adipose Tissue Via the SGLT2 Inhibitor Tofogliflozin
Authors: Yoshida Akihiro , Matsubayashi Yasuhiro , Nojima Toshiaki , Suganami Hideki , Abe Takahiro , Ishizawa Masahiro , Fujihara Kazuya , Tanaka Shiro , Kaku Kohei , Sone Hirohito 
Published: February 2019

Abstract

Context
Although calorie loss from increased urinary glucose excretion continues after long-term treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is), the mechanisms of the attenuated weight loss due to SGLT2is are not well known.

Objective
To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue.

Design and Participants
An integrated analysis was performed using data from two phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of the levels of fasting insulin (f-IRI) and fasting free fatty acids (f-FFAs).

Results
Data from 774 patients with type 2 diabetes (mean age, 58.5 years; glycosylated hemoglobin, 8.1%; body mass index, 25.6 kg/m2; estimated glomerular filtration rate, 83.9 mL/min/1.73m2; 66% men) were analyzed. Weight loss plateaued between weeks 24 and 52 after decreasing significantly. f-IRI levels decreased significantly from baseline to week 24, and the decrease was maintained until Week 52. f-FFA levels significantly increased, peaked at week 24, then declined from weeks 24 to 52. Adipo-IR levels declined progressively throughout the 52 weeks (−3.6 mmol/L·pmol/L and −6.2 mmol/L·pmol/L at weeks 24 and 52, respectively; P < 0.001 baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline Adipo-IR levels were independently associated with greater weight loss at week 52.

Conclusion
The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis, leading to attenuating future weight loss induced by an SGLT2i in patients with type 2 diabetes.
Story of the Eastern Chamber: Dilemmas of Vernacular Language and Political Authority in Eighteenth-Century Chosŏn
Authors: Wang Sixiang 
Published: February 2019

Abstract
The earliest extant playscript in Korea stands as an enigma. It is an anonymous work written to celebrate a wedding arranged by King Chŏngjo. Called Story of the Eastern Chamber, the play evokes not only the Chinese Story of the Western Chamber through titular reference but also the Chinese vernacular tradition as a whole. Written entirely in Chinese characters, the text weaves vernacular Korean words into the syntax of Chinese baihua vernacular, an unusual form which upsets the conventional diglossic binary of literary Chinese (hanmun) and vernacular Korean (hangŭl). This essay situates the text in a late Chosŏn discourse of linguistic difference marked by pronounced anxieties about the temporal and spatial contingency of language. Some late Chosŏn writers, including the text’s putative author, Yi Ok, embraced difference to carve out a localized literary space in Chosŏn Korea. For King Chŏngjo, it threatened the textual foundation of royal authority. Eastern Chamber spoke to these dilemmas by imagining a linguistic space where vernacular Korean usage could be represented as a literary language in the Chinese script, reconciling kingly authority with local specificity.
North Korea’s Marxism-Leninism: Fraternal Criticisms and the Development of North Korean Ideology in the 1960s
Authors: Stock Thomas 
Published: February 2019

Abstract
During the 1960s, as the Sino-Soviet conflict raged on, North Korea, for the first time in its history, officially began to reject the USSR’s ideological leadership and instead tread its own path under the slogan of self-reliance. As a result, those forces aligned with the Soviet Union, especially East Germany, heavily criticized North Korea’s new ideological path. Drawing on the East German archives, this study seeks to understand the nature of fraternal criticisms and their implications for the development of North Korean ideology in the 1960s. Scholars typically stress North Korean ideology’s departure from Marxism-Leninism, sometimes suggesting a departure as early as the 1950s. The present study, based on a thorough reading of archival documents and North Korean materials, challenges such portrayals, arguing that North Korea remained in the Marxist-Leninist tradition even while contesting Soviet orthodoxy. Developments in North Korean ideology were far more gradual than is usually assumed, building on what came before. These developments were by no means revolutionary or removed from the global intellectual environment. The Soviets and East Germans could understand North Korean heterodoxy and engage with it in Marxist-Leninist terms, just as North Korea did with Soviet Marxism-Leninism—there was no fundamental ideological split.
A wave of WNT signaling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells
Authors: Martyn Iain , Brivanlou Ali H. , Siggia Eric D. 
Published: February 2019

ABSTRACT
Long-range signaling by morphogens and their inhibitors define embryonic patterning yet quantitative data and models are rare, especially in humans. Here, we use a human embryonic stem cell micropattern system to model formation of the primitive streak (PS) by WNT. In the pluripotent state, E-cadherin (E-CAD) transduces boundary forces to focus WNT signaling to the colony border. Following application of WNT ligand, E-CAD mediates a front or wave of epithelial-to-mesenchymal (EMT) conversion analogous to PS extension in an embryo. By knocking out the secreted WNT inhibitors active in our system, we show that DKK1 alone controls the extent and duration of patterning. The NODAL inhibitor cerberus 1 acts downstream of WNT to refine the endoderm versus mesoderm fate choice. Our EMT wave is a generic property of a bistable system with diffusion and we present a single quantitative model that describes both the wave and our knockout data.
Obituary: Jarema Malicki (1965-2019)
Authors: Johnson Colin A. 
Published: February 2019

ABSTRACT
Jarema Malicki, a pioneer in developmental studies of the vertebrate retina, died on 4th January 2019, shortly after being diagnosed with cancer. Here, I reflect on Jarema's life and work, with a particular focus on his research interests in zebrafish as a model organism for vertebrate retinogenesis and human ciliopathies.
Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling
Authors: Forte Gabriella M. , Davie Elizabeth , Lie Shervi , Franz-Wachtel Mirita , Ovens Ashley J. , Wang Tingting , Oakhill Jonathan S. , Maček Boris , Hagan Iain M. , Petersen Janni 
Published: February 2019

ABSTRACT
AMP-activated kinase (AMPK) and target of rapamycin (TOR) signalling coordinate cell growth, proliferation, metabolism and cell survival with the nutrient environment of cells. The poor vasculature and nutritional stress experienced by cells in solid tumours raises the question: how do they assimilate sufficient nutrients to survive? Here, we show that human and fission yeast cells import ATP and AMP from their external environment to regulate AMPK and TOR signalling. Exposure of fission yeast (Schizosaccharomyces pombe) and human cells to external AMP impeded cell growth; however, in yeast this restraining impact required AMPK. In contrast, external ATP rescued the growth defect of yeast mutants with reduced TORC1 signalling; furthermore, exogenous ATP transiently enhanced TORC1 signalling in both yeast and human cell lines. Addition of the PANX1 channel inhibitor probenecid blocked ATP import into human cell lines suggesting that this channel may be responsible for both ATP release and uptake in mammals. In light of these findings, it is possible that the higher extracellular ATP concentration reported in solid tumours is both scavenged and recognized as an additional energy source beneficial for cell growth.
PCNT is critical for the association and conversion of centrioles to centrosomes during mitosis
Authors: Kim Jaeyoun , Kim Jeongjin , Rhee Kunsoo 
Published: February 2019

ABSTRACT
A centrosome consists of a pair of centrioles and pericentriolar material (PCM). We manipulated expression of PCNT, a key PCM protein, and investigated roles of PCM in centriole behavior during mitosis. Deletion of PCNT had little effect on interphase centrosomes. However, centrioles in PCNT-deleted mitotic cells prematurely separated and frequently amplified, revealing that centrioles are limited within the spindle poles by PCNT during mitosis. It is known that specific cleavage of PCNT is necessary for centriole separation during mitotic exit. We observed delayed centriole separation in the G0 phase when a non-cleavable mutant form of PCNT was removed or when PCNT was artificially cleaved by TEV protease. Furthermore, a daughter centriole converts to a mother centriole only after experiencing both mitotic exit and specific PCNT cleavage. Based on these results, we propose that a centriole pair disengages upon entering mitosis but remains associated with the surrounding PCM proteins throughout mitosis. During mitotic exit, specific cleavage of PCNT induces PCM disintegration. As a result, a daughter centriole separates from the mother centriole and converts to a young mother centriole.
Nathusius' bats optimize long-distance migration by flying at maximum range speed
Authors: Troxell Sara A. , Holderied Marc W. , Pētersons Gunārs , Voigt Christian C. 
Published: February 2019

ABSTRACTAerial migration is the fastest, yet most energetically demanding way of seasonal movement between habitats. However, for many taxa, and bats in particular, we lack a clear understanding of the energy requirements for migration. Here, we examined the energetic cost and flight speed of the long-distance migratory Nathusius’ bat (Pipistrellus nathusii). We measured flight metabolism in relation to airspeed in a wind tunnel, inferred the optimal traveling speed over long distances, i.e. maximum range speed, and compared this value with flight speed measured in wild conspecifics. Body mass and wing morphologies were similar in captive and wild bats, indicating that the body condition of captive bats was similar to that of migratory bats. Nine out of the 12 captive bats exhibited a U-shaped relationship between flight metabolic power and airspeed when flying in the wind tunnel. The flight metabolic rate across all airspeeds averaged 0.98±0.28 W, which corresponds well to established allometric relationships between flight metabolic rate and body mass for bats. During summer migration, P. nathusii traveled at an average speed of 6.9±0.7 m s−1, which was significantly higher than the minimum power speed (5.8±1.0 m s−1), yet within the range of expected maximum range speed inferred from wind tunnel experiments. This suggests that P. nathusii may migrate at an energetically optimal speed and that aerial refueling does not substantially lower migratory speed in P. nathusii.
Lower leg morphology in runners: forefoot strikers have longer heels but not bigger muscles than rearfoot strikers
Authors: Wessbecher L. S. , Ahn A. N. 
Published: February 2019

ABSTRACT
Foot strike pattern used during running may relate to lower leg morphology. We tested the hypotheses that forefoot strike (FFS) runners have longer plantarflexor moment arms (r) and larger plantarflexor muscles than rearfoot strike (RFS) runners. FFS runners had 17% longer r than RFS runners, but all runners had similarly sized medial and lateral gastrocnemius (MG and LG) muscles. Because muscle size also depends on activation pattern (Ahn et al., 2011), we compared MG:LG activation bias during walking in 24 runners and 23 sedentary subjects. Half of all subjects activated their MG and LG muscles equally (‘unbiased’) while walking, while the other half activated their MG more strongly than their LG muscles (‘MG-biased’). Unbiased sedentary subjects had 16–23% smaller MG muscles compared with MG-biased sedentary subjects, unbiased runners and MG-biased runners. Muscle contraction dynamics during FFS running may balance the effects of longer plantarflexor moment arms in determining MG and LG muscle size.
Conspicuity of suspicious breast lesions on contrast enhanced breast CT compared to digital breast tomosynthesis and mammography
Authors: Aminololama-Shakeri Shadi , Abbey Craig K. , López Javier E , Hernandez Andrew M , Gazi Peymon , Boone John M , Lindfors Karen K 
Published: February 2019

Objective:
Compare conspicuity of suspicious breast lesions on contrast-enhanced dedicated breast CT (CEbCT), tomosynthesis (DBT) and digital mammography (DM).

Methods:
100 females with BI-RADS 4/5 lesions underwent CEbCT and/or DBT prior to biopsy in this IRB approved, HIPAA compliant study. Two breast radiologists adjudicated lesion conspicuity scores (CS) for each modality independently. Data are shown as mean CS ±standard deviation. Two-sided t-test was used to determine significance between two modalities within each subgroup. Multiple comparisons were controlled by the false-discovery rate set to 5%.

Results:
50% of studied lesions were biopsy-confirmed malignancies. Malignant masses were more conspicuous on CEbCT than on DBT or DM (9.7 ±0.5, n = 25; 6.8 ± 3.1, n = 15; 6.7 ± 3.0, n = 27; p &lt; 0.05). Malignant calcifications were equally conspicuous on all three modalities (CEbCT 8.7 ± 0.8, n = 18; DBT 8.5 ± 0.6, n = 15; DM 8.8 ± 0.7, n = 23; p = NS). Benign masses were equally conspicuous on CEbCT (6.6 ± 4.1, n = 22); DBT (6.4 ± 3.8, n = 17); DM (5.9 ± 3.6, n = 24; p = NS). Benign calcifications CS were similar between DBT (8.5 ± 1.0, n = 17) and DM (8.8 ± 0.8, n = 26; p = NS) but less conspicuous on CEbCT (4.0 ± 2.9, n = 25, p &lt; 0.001). 55 females were imaged with all modalities. Results paralleled the entire cohort. 69%(n = 62) of females imaged by CEbCT had dense breasts. Benign/malignant lesion CSs in dense/non-dense categories were 4.8 ± 3.7, n = 33, vs 6.0 ± 3.9, n = 14, p = 0.35; 9.2 ± 0.9, n = 29 vs. 9.4 ± 0.7, n = 14; p = 0.29, respectively.

Conclusion:
Malignant masses are more conspicuous on CEbCT than DM or DBT. Malignant microcalcifications are equally conspicuous on all three modalities. Benign calcifications remain better visualized by DM and DBT than with CEbCT. We observed no differences in benign masses on all modalities. CS of both benign and malignant lesions were independent of breast density.

Advances in knowledge:
CEbCT is a promising diagnostic imaging modality for suspicious breast lesions.