bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal 16q Genomic Loss Implicates Cadherin-11 in Retinoblastoma
Authors: Marchong Mellone N. , Chen Danian , Corson Timothy W. , Lee Cheong , Harmandayan Maria , Bowles Ella , Chen Ning , Gallie Brenda L. 
Published: May 2022

Abstract
Retinoblastoma is initiated by loss of both RB1 alleles. Previous studies have shown that retinoblastoma tumors also show further genomic gains and losses. We now define a 2.62 Mbp minimal region of genomic loss of chromosome 16q22, which is likely to contain tumor suppressor gene(s), in 76 retinoblastoma tumors, using loss of heterozygosity (30 of 76 tumors) and quantitative multiplex PCR (71 of 76 tumors). The sequence-tagged site WI-5835 within intron 2 of the cadherin-11 (CDH11) gene showed the highest frequency of loss (54%, 22 of 41 samples tested). A second hotspot for loss (39%, 9 of 23 samples tested) was detected within intron 2 of the cadherin-13 (CDH13) gene. Furthermore, deletion of the exons of CDH11 and/or WI-5835 was shown by quantitative multiplex PCR in 17 of 30 (57%) of previously untested tumors. Immunoblot analyses revealed that 91% (20 of 22) retinoblastoma exhibited either a complete loss or a decrease of the intact form of CDH11 and 8 of 13 showed a prevalent band suggestive of the variant form. Copy number of WI-5835 for these samples correlated with CDH11 protein expression. CDH11 staining was evident in the inner nuclear layer in early mouse retinal development and in small transgenic murine SV40 large T antigen–induced retinoblastoma tumors, but advanced tumors frequently showed loss of CDH11 expression by reverse transcription-PCR, suggestive of a role for CDH11 in tumor progression or metastasis. CDH13 protein and mRNA were consistently expressed in all human and murine retinoblastoma compared with normal adult human retina. Our analyses implicate CDH11, but not CDH13, as a potential tumor suppressor gene in retinoblastoma.
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Mediated Activation of Mitochondria-Associated Nuclear Factor-κB in Prostatic Carcinoma Cell Lines
Authors: Guseva Natalya V. , Taghiyev Agshin F. , Sturm Mary T. , Rokhlin Oskar W. , Cohen Michael B. 
Published: May 2022

AbstractIt has been suggested that some nuclear transcription factors may participate in the regulation of mitochondrial functions through transcriptional control of mitochondrial DNA. Very little is known about the response of transcription factors within mitochondria to the activation of death receptors. Recent publications indicate that nuclear factor-κB (NF-κB) is localized in mitochondria of mammalian cells. Because of the critical role of mitochondria in the execution of many apoptotic pathways, we suggest that NF-κB-dependent mechanisms operating at the level of mitochondria contribute to its role in regulating death receptor signaling. We have found NF-κB p65 and p50 subunits with DNA binding activity in the mitochondria of prostatic carcinoma cell lines. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) affects DNA binding activity of mitochondria-associated NF-κB but does not change the amount of p65 in mitochondria, which suggests activation of mitochondrial NF-κB without additional translocation of NF-κB subunits to mitochondria. We have also shown that TRAIL decreases mitochondrial genome encoded mRNA levels and inhibition of NF-κB prevents this decrease. TRAIL effects on mitochondrial NF-κB-DNA binding and mitochondrial genome encoded mRNA levels also depend on Bcl-2 overexpression. In addition, transcription factor activator protein-1 with DNA binding activity is also found in mitochondria of prostatic carcinoma cells and TRAIL treatment affects this binding. In summary, NF-κB is found in mitochondria of prostatic carcinoma cells, where it is thought to regulate mitochondria genome encoded mRNA levels in response to TRAIL treatment.
Exogenous Fibroblast Growth Factors Maintain Viability, Promote Proliferation, and Suppress GADD45α and GAS6 Transcript Content of Prostate Cancer Cells Genetically Modified to Lack Endogenous FGF-2
Authors: Shain Sydney A. 
Published: May 2022

Abstract
Understanding processes regulating prostate cancer cell survival is critical to management of advanced disease. We used prostate cancer cell transfectants genetically modified to be deficient in either endogenous fibroblast growth factor (FGF-1) or endogenous FGF-2 to examine FGF maintenance of transfectant survival and proliferation and FGF-2-regulated expression of transfectant growth arrest DNA damage (GADD) and growth arrest sequences (GAS) family genes (known modulators of cell cycle progression and survival) and the AS3 gene (an androgen-modulated effector of prostate cell proliferation). When propagated in the absence of exogenous FGFs, FGF-2-deficient transfectants undergo exponential death, whereas FGF-1-deficient transfectants proliferate. Exogenous FGF-1, FGF-2, FGF-7, or FGF-8 promote survival and proliferation of FGF-2-deficient transfectants and enhance FGF-1-deficient transfectant proliferation. Transfectants express FGF receptor FGFR1, FGFR2(IIIb), FGFR2(IIIc), and FGFR3 transcripts, findings consistent with the effects of exogenous FGFs. FGF-2-deficient transfectants express high levels of AS3, GADD45α, GADD45γ, GAS8, and GAS11 transcripts and moderate levels of GADD153, GAS2, GAS3, and GAS6 transcripts and lack demonstrable GAS1 or GAS5 transcripts. FGF withdrawal-mediated death of FGF-2-deficient transfectants did not significantly affect cell AS3, GADD153, GADD45γ, GAS2, GAS3, GAS7, GAS8, or GAS11 transcript content, whereas GADD45α and GAS6 transcript content was elevated. These studies establish that endogenous FGF-2 dominantly regulates prostate cancer cell survival and proliferation and that exogenous FGFs may assume this function in the absence of endogenous FGF-2. Additionally, we provide the first evidence that FGFs regulate prostate GADD45α and GAS6 transcript content. The latter observations suggest that GADD45α and GAS6 proteins may be effectors of processes that regulate prostate cancer cell survival. Additional studies are required to examine this possibility in detail.
Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study
Authors: Tortigue Marine , Nield Lynne E. , Karakachoff Matilde , McLeod Christopher J. , Belli Emre , Babu-Narayan Sonya V. , Prigent Solène , Boet Angèle , Conway Miriam , Elder Robert W. , Ladouceur Magalie , Khairy Paul , Kowalik Ewa , Kalfa David M. , Barron David J. , Mussa Shafi , Hiippala Anita , Temple Joel , Abadir Sylvia , Le Gloan Laurianne , Lachaud Matthias , Sanatani Shubhayan , Thambo Jean-Benoit , Gronier Céline Grunenwald , Amedro Pascal , Vaksmann Guy , Charbonneau Anne , Koutbi Linda , Ovaert Caroline , Houeijeh Ali , Combes Nicolas , Maury Philippe , Duthoit Guillaume , Hiel Bérengère , Erickson Christopher C. , Bonnet Caroline , Van Hare George F. , Dina Christian , Karsenty Clément , Fournier Emmanuelle , Le Bloa Mathieu , Pass Robert H. , Liberman Leonardo , Happonen Juha-Matti , Perry James C. , Romefort Bénédicte , Benbrik Nadir , Hauet Quentin , Fraisse Alain , Gatzoulis Michael A. , Abrams Dominic J. , Dubin Anne M. , Ho Siew Yen , Redon Richard , Bacha Emile A. , Schott Jean-Jacques , Baruteau Alban-Elouen 
Published: May 2022

Background:
Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns.

Methods:
An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands.

Results:
Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia.

Conclusions:
ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.
Abstract 241: Length Of Hospital Stay Is Lessened In Patients That Present With Chest Pain When Serial Troponins Are Measured Every Three Hours Compared To Every Six Hours
Authors: Grees Andrew , Lachhar Garry G , Mahbub Elnaz , Saxby Kathryn , Kim Anita , Beard Meghan , Kazi Ananna , Lamar Katie , Melek Andrew , Joshi Raj , Lubrano Lavadera Mariana , Reilly John P 
Published: May 2022

Troponins have close to 100% sensitivity when drawn 6 to 12 hours after the start of chest pain in acute coronary syndrome (ACS). Length of hospital stay (LOS) is a marker of efficient hospital management. Since troponin measurements at 3 (Q3H) and 6-hour (Q6H) intervals have comparable efficacy for ACS, we suggest considering Q3H troponins as opposed to Q6H in chest pain admissions to shorten LOS.
A retrospective review of 389 patients who presented to Stony Brook Southampton Hospital in 2020 and 2021 with chest pain was conducted. Two patient care strategies were examined, one involved collecting troponins Q6H and the other Q3H. 319 patients with the Q6H strategy were analyzed and 61.1% were ruled in for ACS. For the Q3H strategy, 70 patients were analyzed in which 42.9% were ruled in for ACS. LOS was defined as hours between triage and submission of discharge instructions. A two-sample t-test was performed to find correlation between frequency of troponins and LOS.
A two-sample t-test assuming unequal variance was conducted to compare LOS in hours between Q6H and Q3H strategies. There was a significant difference in LOS for Q6H (M = 123, SD = 201) and Q3H (M = 66, SD = 135) troponins; t = 2.91, p = 0.002. These results suggest that LOS is lessened when troponin intervals are shorter. The variance was elevated (40249,18343), possibly due to patients who stayed longer for other needs, but mean LOS and standard deviation remained decreased both when excluding patients that stayed longer than one week, and when including all patients in the analysis.
Optimizing LOS has a variety of benefits. In patients with chest pain, shortening the interval of troponin collection can lessen LOS. Studies of comparable efficacy of shorter troponin intervals in evaluation of ACS have led to the practice of trending at Q3H intervals in Europe. Our study demonstrates that trending troponins Q3H is viable in a community hospital in the United States and should be further investigated and considered in the future.
Abstract 243: Length Of Hospital Stay Is Lessened In Patients That Present With Chest Pain When Admitted To The Cardiology Service Compared To Other Services Within Our Teaching Hospital
Authors: Lachhar Garry G , Mahbub Elnaz , Grees Andrew , Kim Anita , Saxby Kathryn , Beard Meghan , Blair Jeffrey , Melek Andrew , Seligson John , Gul Rahat , McCarthy Michael , Reilly John P 
Published: May 2022

Length of stay (LOS) in the hospital for patients presenting with chest pain can be influenced by several factors. In patients evaluated for acute coronary syndrome (ACS), admission to a cardiology service may allow patients to have a shorter LOS, while admission to a non-specialty service has been shown to potentially cause worse outcomes. In this analysis, we evaluate whether specialized care decreases LOS in patients who present with chest pain.
A retrospective review of 389 patients who presented to Stony Brook Southampton Hospital in 2020 and 2021 with chest pain and underwent ACS evaluation was conducted. The two strategies involved admissions to the cardiology service or to other hospital services. We analyzed 95 cardiology admissions, 56.8% of which ruled in for ACS, and 294 admissions to other hospital services, 58.2% of which ruled in for ACS. LOS was defined as hours between triage and submission of discharge instructions. A two-sample t-test was performed to find correlations between admission service and length of hospital stay.
A two-sample t-test assuming unequal variance was conducted to compare LOS in hours between patients admitted to the cardiology and non-cardiology services. There was a significant difference in LOS for the cardiology service (M = 48, SD = 55) and non-cardiology service (M = 134, SD = 214) conditions; t = 6.30, p < 0.001. These results suggest that LOS is lessened when chest pain patients are admitted to the cardiology service. The variance was elevated (2985, 45849), possibly due to patients who stayed longer for other needs, but mean LOS and SD remained decreased when excluding patients that stayed longer than one week, and when including all patients in the analysis.
When admitting a patient, there are many ways to optimize LOS. Admission of patients who present with chest pain to a specialty cardiology service may allow patients to have a more efficient LOS and should be further investigated and considered in the future.
Beyond the Golden Hour: Treating Acute Stroke in the Platinum 30 Minutes
Authors: Randhawa Anantbir S. , Pariona-Vargas Fatima , Starkman Sidney , Sanossian Nerses , Liebeskind David S. , Avila Gilda , Stratton Samuel , Gornbein Jeffrey , Sharma Latisha , Restrepo-Jimenez Lucas , Valdes-Sueiras Miguel , Kim-Tenser May , Villablanca Pablo , Conwit Robin , Hamilton Scott , Saver Jeffrey L. 
Published: May 2022

Background:
To emphasize treatment speed for time-sensitive conditions, emergency medicine has developed not only the concept of the golden hour, but also the platinum half-hour. Patients with acute stroke treated within the first half-hour of onset have not been previously characterized.

Methods:
In this cohort study, we analyzed patients enrolled in the FAST-MAG (Field Administration of Stroke Therapy–Magnesium) trial, testing paramedic prehospital start of neuroprotective agent ≤2 hours of onset. The features of all acute cerebral ischemia, and intracranial hemorrhage patients with treatment starting at ≤30 m of last known well were compared with later-treated patients.

Results:
Among 1680 patients, 203 (12.1%) received study agents within 30 minutes of last known well. Among platinum half-hour patients, median onset-to-treatment time was 28 minutes (interquartile range, 25–30), and final diagnoses were acute cerebral ischemia in 71.8% (ischemic stroke, 61.5%, TIA 10.3%); intracranial hemorrhage in 26.1%; and mimic in 2.5%. Clinical features among platinum half-hour patients were largely similar to later-treated patients and included age 69 (interquartile range, 57–79), 44.8% women, prehospital Los Angeles Motor Scale median 4 (3–5), and early-postarrival National Institutes of Health Stroke Scale deficit 8 (interquartile range, 3–18). Platinum half-hour acute cerebral ischemia patients did have more severe prehospital motor deficits and younger age; platinum half-hour intracranial hemorrhage patients had more severe motor deficits, were more often female, and less often of Hispanic ethnicity. Outcomes at 3 m in platinum half-hour patients were comparable to later-treated patients and included freedom-from-disability (modified Rankin Scale score, 0–1) in 35.5%, functional independence (modified Rankin Scale score, 0–2) in 53.2%, and mortality in 17.7%.

Conclusions:
Prehospital initiation permits treatment start within the platinum half-hour after last known well in a substantial proportion of acute ischemic and hemorrhagic stroke patients, accounting for more than 1 in 10 enrolled in a multicenter trial. Hyperacute platinum half-hour patients were largely similar to later-treated patients and are an attainable target for treatment in prehospital stroke trials.
Pier Competitor: China's Power Position in Global Ports
Authors: Kardon Isaac B. , Leutert Wendy 
Published: May 2022

Abstract
China is a leader in the global transportation industry, with an especially significant position in ocean ports. A mapping of every ocean port outside of China reveals that Chinese firms own or operate terminal assets in ninety-six ports in fifty-three countries. An original dataset of Chinese firms' overseas port holdings documents the geographic distribution, ownership, and operational characteristics of these ports. What are the international security implications of China's global port expansion? An investigation of Chinese firms' ties to the Party-state reveals multiple mechanisms by which the Chinese leadership may direct the use of commercial port assets for strategic purposes. International port terminals that Chinese firms own and operate already provide dual-use capabilities to the People's Liberation Army during peacetime, establishing logistics and intelligence networks that materially enable China to project power into critical regions worldwide. But this form of networked state power is limited in wartime because it depends on commercial facilities in non-allied states. By providing evidence that overseas bases are not the sole index of global power projection capabilities, findings advance research on the identification and measurement of sources of national power. China's leveraging of PRC firms' transnational commercial port network constitutes an underappreciated but consequential form of state power projection.
Toward a Social History of Modern Chinese Warlordism
Authors: McCord Edward A. 
Published: May 2022

Abstract
The social impact of modern Chinese warlordism on China’s modern development has attracted little attention in past scholarship, which generally has been more interested in warlordism as a military-political system. This article argues, however, that warlordism developed within a social context and had a major impact on Chinese society, and this in turn suggests the usefulness of applying a social history approach to the study of the warlord period. This article makes a preliminary effort to advance this goal by identifying three main areas that could provide a framework for research on the social history of Chinese warlordism. First, the article examines debates over the social (or class) foundations of warlord power. Second, the article explores the ways in which warlordism changed the social status of military men and created opportunities for social mobility. Finally, the article emphasizes the need to look beyond the political impact of Chinese warlordism to show the social and economic effects that arose from the military conflicts of the warlord era.
On Characterizing Ocean Kinematics from Surface Drifters
Authors: Essink Sebastian , Hormann Verena , Centurioni Luca R. , Mahadevan Amala 
Published: May 2022

Abstract
Horizontal kinematic properties, such as vorticity, divergence, and lateral strain rate, are estimated from drifter clusters using three approaches. At submesoscale horizontal length scales , kinematic properties become as large as planetary vorticity f, but challenging to observe because they evolve on short time scales . By simulating surface drifters in a model flow field, we quantify the sources of uncertainty in the kinematic property calculations due to the deformation of cluster shape. Uncertainties arise primarily due to (i) violation of the linear estimation methods and (ii) aliasing of unresolved scales. Systematic uncertainties (iii) due to GPS errors, are secondary but can become as large as (i) and (ii) when aspect ratios are small. Ideal cluster parameters (number of drifters, length scale, and aspect ratio) are determined and error functions estimated empirically and theoretically. The most robust method—a two-dimensional, linear least squares fit—is applied to the first few days of a drifter dataset from the Bay of Bengal. Application of the length scale and aspect-ratio criteria minimizes errors (i) and (ii), and reduces the total number of clusters and so computational cost. The drifter-estimated kinematic properties map out a cyclonic mesoscale eddy with a surface, submesoscale fronts at its perimeter. Our analyses suggest methodological guidance for computing the two-dimensional kinematic properties in submesoscale flows, given the recently increasing quantity and quality of drifter observations, while also highlighting challenges and limitations.

Significance Statement
The purpose of this study is to provide insights and guidance for computing horizontal velocity gradients from clusters (i.e., three or more) of Lagrangian surface ocean drifters. The uncertainty in velocity gradient estimates depends strongly on the shape deformation of drifter clusters by the ocean currents. We propose criteria for drifter cluster length scales and aspect ratios to reduce uncertainties and develop ways of estimating the magnitude of the resulting errors. The findings are applied to a real ocean dataset from the Bay of Bengal.
Stratospheric Observations of Corona Current from Loon’s Superpressure Balloons
Authors: Reid Beth , Swanson Tom 
Published: May 2022

Abstract
Loon LLC collected 794 000 h of corona current observations between 15 and ∼20 km above sea level with time resolution between 1 and 30 min. We are publicly releasing this dataset to enable the research community’s understanding of electrical activity in the stratosphere. We validate the reliability of these measurements by aligning our flight data with both nearby Geostationary Lightning Mapper (GLM) events and the Convective Diagnostic Oceanic (CDO) indicator. Corona current observations that exceeded the sensor maximum of 10 μA were associated with high GLM optical flux accumulations along the flight trajectory. Using the CDO indicator as a persistence forecast for future electrical activity was effective at predicting corona current events, and so we highly recommend this data source for real-time stratospheric navigation for vehicles sensitive to the harsh electrical environment of the stratosphere.

Significance Statement
Loon LLC operated a fleet of balloons in the stratosphere, between 15 and 20 km above sea level. The balloons were instrumented with a sensor that measured the current flowing through a wire dangling from the flight vehicle. The observed currents were caused by the motion of nearby charged particles that are often associated with thunderstorms and lightning activity. In this paper we show that Loon’s sensor registered current at the same time lightning was recorded near the balloon by other instruments like the Geostationary Lightning Mapper satellite. This is the first dataset of its kind and size, reaching 794 000 flight hours. We are publicly releasing these data in hopes of aiding scientific discovery by researchers and to help future stratospheric vehicle operators better understand and plan for the electrical environment.