bluuebunny/crossref_metadata_2025_split huggingface dataset:
SOCS1 Gene Therapy Improves Radiosensitivity and Enhances Irradiation-Induced DNA Damage in Esophageal Squamous Cell Carcinoma
Authors: Sugase Takahito , Takahashi Tsuyoshi , Serada Satoshi , Fujimoto Minoru , Hiramatsu Kosuke , Ohkawara Tomoharu , Tanaka Koji , Miyazaki Yasuhiro , Makino Tomoki , Kurokawa Yukinori , Yamasaki Makoto , Nakajima Kiyokazu , Kishimoto Tadamitsu , Mori Masaki , Doki Yuichiro , Naka Tetsuji 
Published: October 2017

Abstract
STAT3 has been implicated recently in radioresistance in cancer. In this study, we investigated the association between STAT3 and radioresistance in esophageal squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p-STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy (CRT), compared with 9 of 24 patients with surgery alone, where the prognosis of those with CRT was poor. Expression of p-STAT3 and the antiapoptotic proteins Mcl-1 and survivin was strongly induced in ESCC cells by irradiation. Ectopic STAT3 expression increased radioresistance, whereas expression of the STAT3 negative regulator SOCS1 via an adenoviral vector improved radioresponse. Inhibiting the STAT3–Mcl-1 axis by SOCS1 enhanced DNA damage after irradition and induced apoptosis. Combining SOCS1 with radiotherapy enhanced antitumor responses in a murine xenograft model compared with the individual therapies. Tumor repopulation occurred transiently after treatment by irradiation but not the combination SOCS1/radiotherapy. Tumors subjected to this combination expressed high levels of γH2AX and low levels of Ki-67, which was maintained after cessation of treatment. Overall, we demonstrated that inhibiting the STAT3–Mcl-1 signaling axis by ectopic SOCS1 improved radiosensitivity by inducing apoptosis and enhancing DNA damage after radiotherapy, offering a mechanistic rationale for a new ESCC treatment. Cancer Res; 77(24); 6975–86. ©2017 AACR.
Predictors of Death in Adults With Duchenne Muscular Dystrophy–Associated Cardiomyopathy
Authors: Cheeran Daniel , Khan Shaida , Khera Rohan , Bhatt Anish , Garg Sonia , Grodin Justin L. , Morlend Robert , Araj Faris G. , Amin Alpesh A. , Thibodeau Jennifer T. , Das Sandeep , Drazner Mark H. , Mammen Pradeep P. A. 
Published: October 2017

Background

Duchenne muscular dystrophy (
DMD
) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to
DMD
patients over the past 2 decades, there remains a group of
DMD
patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult
DMD
patients.

Methods and Results

A retrospective cohort of 43 consecutive patients was followed in the adult
UT
Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The
DMD
population was in the early 20s, with median follow‐up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin‐converting enzyme inhibitors (86%) and steroids (56%), but few other guideline‐directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8–19.3] versus 25.8 [20.8–29.1] kg/m
2
,
P
<0.01), alanine aminotransferase levels (26 [18–42] versus 53 [37–81] units/L,
P
=0.001), maximum inspiratory pressures (13 [0–30] versus 33 [25–40] cmH
2
O,
P
=0.03), and elevated cardiac biomarkers (N‐terminal pro‐brain natriuretic peptide: 288 [72–1632] versus 35 [21–135] pg/mL,
P
=0.03].

Conclusions

The findings demonstrate a
DMD
population with a high burden of cardiomyopathy. The nonsurviving cohort was comparatively underweight, and had worse respiratory profiles and elevated cardiac biomarkers. Collectively, these factors highlight a high‐risk cardiovascular population with a worse prognosis.
Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men
Authors: Dalmasso Carolina , Patil Chetan N. , Yanes Cardozo Licy L. , Romero Damian G. , Maranon Rodrigo O. 
Published: October 2017

Background

The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (
SHR)
, long‐term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin‐angiotensin system.

Methods and Results

In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks‐
YMSHR
) and old (21–22 months‐
OMSHR
) male
SHR
that increased serum testosterone by 2‐fold in young males and by 4‐fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in
YMSHR
but had no effect in
OMSHR
. Mean arterial pressure (
MAP
) was significantly higher in
OMSHR
than in
YMSHR
and testosterone supplements decreased
MAP
in
OMSHR
, but significantly increased
MAP
in
YMSHR
. Enalapril, the angiotensin‐converting enzyme inhibitor, reduced
MAP
in both control and testosterone‐supplemented
YMSHR
, but had a greater effect on
MAP
in testosterone‐treated rats, suggesting the mechanism responsible for the increase in
MAP
in
YMSHR
is mediated at least in part by activation of the renin‐angiotensin system.

Conclusions
Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long‐term or short‐term.
Relative Survival After Transcatheter Aortic Valve Implantation: How Do Patients Undergoing Transcatheter Aortic Valve Implantation Fare Relative to the General Population?
Authors: Martin Glen P. , Sperrin Matthew , Hulme William , Ludman Peter F. , de Belder Mark A. , Toff William D. , Alabas Oras , Moat Neil E. , Doshi Sagar N. , Buchan Iain , Deanfield John E. , Gale Chris P. , Mamas Mamas A. ,   the National Institute of Cardiovascular Outcomes Research (NICOR)
Published: October 2017

Background

Transcatheter aortic valve implantation (
TAVI
) is indicated for patients with aortic stenosis who are intermediate‐high surgical risk. Although all‐cause mortality rates after
TAVI
are established, survival attributable to the procedure is unclear because of competing causes of mortality. The aim was to report relative survival (
RS
) after
TAVI
, which accounts for background mortality risks in a matched general population.

Methods and Results

National cohort data (n=6420) from the 2007 to 2014
UK TAVI
registry were matched by age, sex, and year to mortality rates for England and Wales (population, 57.9 million). The Ederer
II
method related observed patient survival to that expected from the matched general population. We modelled
RS
using a flexible parametric approach that modelled the log cumulative hazard using restricted cubic splines. RS of the
TAVI
cohort was 95.4%, 90.2%, and 83.8% at 30 days, 1 year, and 3 years, respectively. By 1‐year follow‐up, mortality hazards in the >85 years age group were not significantly different from those of the matched general population; by 3 years, survival rates were comparable. The flexible parametric
RS
model indicated that increasing age was associated with significantly lower excess hazards after the procedure; for example, by 2 years, a 5‐year increase in age was associated with 20% lower excess mortality over the general population.

Conclusions

RS
after
TAVI
was high, and survival rates in those aged >85 years approximated those of a matched general population within 3 years. High rates of
RS
indicate that patients selected for
TAVI
tolerate the risks of the procedure well.
Intersectionality, Gender Liminality and Ben Sira’s Attitude to the Eunuch
Authors: Bolle Helena M. , Llewelyn Stephen R. 
Published: October 2017

Abstract
Ben Sira twice cites the eunuch in sayings that play on his sexual impotence. In so doing he diverges from what we know of the Hebraic tradition before him. Blending theory is used to interpret the sayings and their apparently malicious intent. After appraising the ambiguous status/identity of the eunuch in terms of ‘intersectionality’, Ben Sira’s attitude is contextualised using the concepts of ‘gender liminality’ and ‘hybridity’ and set against the strict binary system that underlies his understanding of gender more generally. It is suggested that Ben Sira’s theology of creation, like that of the Wisdom tradition more generally, forms the principal basis for this binary system. At the same time, the more accepting attitude to the eunuch in Isaiah 56 is considered and its notion of the ‘new creation’.
Ezra in Egypt? The Significance of Hananyah’s Mission
Authors: van der Toorn Karel 
Published: October 2017

Abstract
The history of the Jewish community at Elephantine plays a crucial role in the reconstruction of the early history of Judaism. One document in particular sheds a light on the emerging Jewish identity in the diaspora. It is Hananyah’s so-called Passover Letter. This contribution investigates the significance of Hananyah’s mission in Egypt, and more particularly its relationship with the missions of Ezra and Nehemiah. The investigation permits three conclusions. One, the Persians did not distinguish between ethnicity and religion; two, the codification of Jewish ritual preceded the codification of the Torah; and three, Jewish identity in the late 5th century allowed significant latitude in matters of doctrine and lifestyle.
On the Compositional Models for Ezekiel 38-39: A Response to William Tooman’s Gog of Magog
Authors: Strine C. A. 
Published: October 2017

Abstract
William Tooman’s monograph Gog of Magog: Reuse of Scripture and Compositional Technique in Ezekiel 38-39 has quickly become a seminal study of Ezek 38-39. This article examines and critiques Tooman’s influential position that Ezek 38-39 were composed by a method called thematic pastiche, which only emerged in second temple Jewish texts. By showing inconsistencies in the limits of what constitutes thematic pastiche and by re-examining the evidence that Ezek 38-39 depends upon Joel 1:6; 2:27; 3:1-2; Isa 62:2; 66:18-19, this article demonstrates that Joel 3:1-2 and Isa 66:18-19 may even reuse Ezek 39:21, 29 as source texts, thus re-opening the search for which texts provide the compositional model for the Gog oracles. As a logical consequence of that finding, this article highlights problems with Tooman’s widely adopted proposal, albeit provisional, that Ezek 38-39 dates from the 4th to 2nd century bce.
Ritual Consecration in the Context of Writing the Holy Scrolls: Jews in Medieval Europe between Demarcation and Acculturation
Authors: Martini Annett 
Published: October 2017

Abstract
The objective of this article is to outline a hitherto neglected aspect of writing holy scrolls for ritual use, which in medieval Europe became a crucial subject of discussion: the ritual consecration of certain processes during the manufacturing of STaM with a special emphasis on writable skins. Taking into account Jewish and Christian sources, many of which have not been scrutinized to date, a paradox that perfectly reflects the ambivalent relationship of Jews and Christians in the Middle Ages will be revealed. On the one hand, the ritual sanctification can be read as an act of demarcation by which Jews drew a clear line between holy and profane—and Jews and non-Jews. On the other hand, it becomes evident that there was not only an artisanal exchange but a mutual interaction in terms of ritual and performance as well.
Abuse of Diplomatic Privileges and the Balance between Immunities and the Duty to Respect the Local Laws and Regulations under the Vienna Conventions: The Recent Indian Experience
Authors: Subramanian S. R. 
Published: October 2017

Abstract
The successful adoption of the Vienna Convention on Diplomatic Relations is hailed as the ‘landmark of the highest significance in the codification of international law’. It represented the first significant codification of any international instrument since the United Nations was established. However, despite the codification of the above rules, which is largely based on the pre-existing customary international law, the scope of diplomatic protection was not free from issues and controversies. In recent times, unfortunately, there is a growing tendency amongst the diplomats to abuse their diplomatic status to commit acts prohibited by law and still claim immunity from legal process. The States-parties also aggravate this situation by selectively interpreting the rules in their favor, ignoring the fact that reciprocity is the basis for the successful functioning of the diplomatic protection. In this connection, this paper addresses the problem of abuse of immunities and privileges and its adverse implications on the balance between immunities and the duty to respect the local laws and regulations, especially with special reference to the recent Indian experience. It explores the two recent Indian diplomatic confrontations, namely, the arrest of Devyani Khobragade and the travel ban on Daniele Mancini. Based on the study, it highlights the need for a well-balanced and equitable enforcement of the Vienna Conventions in the interest of maintenance of cordial diplomatic relations in the international community.
The Juridification of Religion?
Authors: Årsheim Helge , Slotte Pamela 
Published: October 2017

AbstractThis article sets out to explore the extent to which developments currently taking place at the interface between law and religion in domestic, regional and international law can be conceptualized as instances of larger, multidimensional processes of juridification. We rely on an expansive notion of juridification, departing from the more narrow sense of juridificiation as the gradually increasing “colonization of the lifeworld” proposed by Jürgen Habermas in his Theory of Communicative Action (1987; Vol. 2, Beacon Press). More specifically, the article adapts the multidimensional notion of juridification outlined by Anders Molander and Lars Christian Blichner in their article ‘Mapping Juridification’ (2008; 14 European Law Journal 36), and develops it into a more context-specific notion of juridification that is attendant to the specific nature of religion as a subject matter for law.
General outcomes and risk factors for minor and major amputations in Brazil
Authors: Leite Jose O , Costa Leandro O , Fonseca Walter M , Souza Debora U , Goncalves Barbara C , Gomes Gabriela B , Cruz Lucas A , Nister Nilder , Navarro Tulio P , Bath Jonathan , Dardik Alan 
Published: October 2017

Objectives Major and minor amputations are associated with significant rates of mortality. However, little is known about the impact of unplanned redo-amputation during the same hospitalization on outcomes. The objectives of this study were to identify the risk factors associated with in-hospital mortality after both major and minor amputations as well as the results of unplanned redo-amputation on outcome. Methods Retrospective study of 342 consecutive patients who were treated with lower extremity amputation in Brazil between January 2013 and October 2014. Results The in-hospital mortality rate was higher in major compared to minor amputation (25.6% vs. 4.1%; p < 0.0001). Whereas chronic kidney disease, chronic obstructive pulmonary disease, and planned staged amputation predicted in-hospital mortality after major amputation, age, and congestive heart failure predicted mortality after minor amputation. The white blood cell count predicted in-hospital mortality following both major and minor amputation. However, postoperative infection predicted in-hospital mortality only following major amputation. Conclusions In-hospital mortality was high after major amputations. Unplanned redo-amputation was not a predictor of in-hospital mortality after major or minor amputation. Planned staged amputation was associated with reduced survival after major but not minor amputation. Postoperative infection predicted mortality after major amputation. Systemic diseases and postoperative white blood cell were associated with in-hospital mortality. This study suggests a possible link between a pro-inflammatory state and increased in-hospital mortality following amputation.
Emicizumab, a bispecific antibody recognizing coagulation factors IX and X: how does it actually compare to factor VIII?
Authors: Lenting Peter J. , Denis Cécile V. , Christophe Olivier D. 
Published: October 2017

AbstractDuring the last decade, the development of improved and novel approaches for the treatment of hemophilia A has expanded tremendously. These approaches include factor VIII (FVIII) with extended half-life (eg, FVIII-Fc and PEGylated FVIII), monoclonal antibodies targeting tissue factor pathway inhibitor, small interfering RNA to reduce antithrombin expression and the bispecific antibody ACE910/emicizumab. Emicizumab is a bispecific antibody recognizing both the enzyme factor IXa and the substrate factor X. By simultaneously binding enzyme and substrate, emicizumab mimics some part of the function exerted by the original cofactor, FVIII, in that it promotes colocalization of the enzyme–substrate complex. However, FVIII and the bispecific antibody are fundamentally different proteins and subject to different modes of regulation. Here, we will provide an overview of the similarities and dissimilarities between FVIII and emicizumab from a biochemical and mechanistical perspective. Such insight might be useful in the clinical decision making for those who apply emicizumab in their practice now or in the future, particularly in view of the thrombotic complications that have been reported when emicizumab is used in combination with FVIII-bypassing agents.
Obesity in individuals with schizophrenia: a case controlled
study in Scotland
Authors: Cameron Isobel M. , Hamilton Ross J. , Fernie Gordon , MacGillivray Stephen A. 
Published: October 2017

BackgroundDespite extensive clinical concern about rates of obesity in patients
with schizophrenia, there is little evidence of the extent of this
problem at a population level.AimsTo estimate levels of obesity in a national population sample by
comparing patients with schizophrenia with matched controls.MethodWe calculated levels of obesity for each patient with schizophrenia from
the national Primary Care Clinical Informatics Unit database (n=4658)
matched with age, gender and neighbourhood controls.ResultsWe demonstrated a significant increased obesity hazard for the
schizophrenia group using Cox regression analysis, with odds ratio (OR)
of 1.94 (95% CI 1.81–2.10) (under the assumption of missing body mass
index (BMI) indicating non-obesity) and OR=1.68 (95% CI 1.55–1.81) where
no assumptions were made for missing BMI data.ConclusionsPeople with schizophrenia are at increased risk of being obese compared
with controls matched by age, gender and practice attended. Priority
should be given to research which aims to reduce weight and increase
activity in those with schizophrenia.
It's just sand between the toes: how particle size and shape variation affect running performance and kinematics in a generalist lizard
Authors: Bergmann Philip J. , Pettinelli Kyle J. , Crockett Marian E. , Schaper Erika G. 
Published: October 2017

ABSTRACTAnimals must cope with and be able to move effectively on a variety of substrates. Substrates composed of granular media, such as sand and gravel, are extremely common in nature, and vary tremendously in particle size and shape. Despite many studies of the properties of granular media and comparisons of locomotion between granular and solid substrates, the effects of systematically manipulating these media on locomotion is poorly understood. We studied granular media ranging over four orders of magnitude in particle size, and differing in the amount of particle shape variation, to determine how these factors affected substrate physical properties and sprinting in the generalist lizard Eremias arguta. We found that media with intermediate particle sizes had high bulk densities, low angles of stability and low load-bearing capacities. Rock substrates with high shape variation had higher values for all three properties than glass bead substrates with low shape variation. We found that E. arguta had the highest maximum velocities and accelerations on intermediate size particles, and higher velocities on rock than glass beads. Lizards had higher stride frequencies and lower duty factors on intermediate particle size substrates, but their stride lengths did not change with substrate. Our findings suggest that sand and gravel may represent different locomotor challenges for animals. Sand substrates provide animals with an even surface for running, but particles shift underfoot. In contrast, gravel particles are heavy, so move far less underfoot, yet provide the animal with an uneven substrate.
Skeletal stiffening in an amphibious fish out of water is a response to increased body weight
Authors: Turko Andy J. , Kültz Dietmar , Fudge Douglas , Croll Roger P. , Smith Frank M. , Stoyek Matthew R. , Wright Patricia A. 
Published: October 2017

ABSTRACTTerrestrial animals must support their bodies against gravity, while aquatic animals are effectively weightless because of buoyant support from water. Given this evolutionary history of minimal gravitational loading of fishes in water, it has been hypothesized that weight-responsive musculoskeletal systems evolved during the tetrapod invasion of land and are thus absent in fishes. Amphibious fishes, however, experience increased effective weight when out of water – are these fishes responsive to gravitational loading? Contrary to the tetrapod-origin hypothesis, we found that terrestrial acclimation reversibly increased gill arch stiffness (∼60% increase) in the amphibious fish Kryptolebias marmoratus when loaded normally by gravity, but not under simulated microgravity. Quantitative proteomics analysis revealed that this change in mechanical properties occurred via increased abundance of proteins responsible for bone mineralization in other fishes as well as in tetrapods. Type X collagen, associated with endochondral bone growth, increased in abundance almost ninefold after terrestrial acclimation. Collagen isoforms known to promote extracellular matrix cross-linking and cause tissue stiffening, such as types IX and XII collagen, also increased in abundance. Finally, more densely packed collagen fibrils in both gill arches and filaments were observed microscopically in terrestrially acclimated fish. Our results demonstrate that the mechanical properties of the fish musculoskeletal system can be fine-tuned in response to changes in effective body weight using biochemical pathways similar to those in mammals, suggesting that weight sensing is an ancestral vertebrate trait rather than a tetrapod innovation.