bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of Distinct ShcA Signaling Complexes Promotes Breast Tumor Growth and Tyrosine Kinase Inhibitor Resistance
Authors: Ha Jacqueline R. , Ahn Ryuhjin , Smith Harvey W. , Sabourin Valerie , Hébert Steven , Cepeda Cañedo Eduardo , Im Young Kyuen , Kleinman Claudia L. , Muller William J. , Ursini-Siegel Josie 
Published: February 2018

Abstract
The commonality between most phospho-tyrosine signaling networks is their shared use of adaptor proteins to transduce mitogenic signals. ShcA (SHC1) is one such adaptor protein that employs two phospho-tyrosine binding domains (PTB and SH2) and key phospho-tyrosine residues to promote mammary tumorigenesis. Receptor tyrosine kinases (RTK), such as ErbB2, bind the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling. However, breast tumors also rely on the ShcA PTB domain to bind numerous negative regulators that limit activation of secondary mitogenic signaling networks. This study examines the role of PTB-independent ShcA pools in controlling breast tumor growth and resistance to tyrosine kinase inhibitors. We demonstrate that PTB-independent ShcA complexes predominately rely on the ShcA SH2 domain to activate multiple Src family kinases (SFK), including Src and Fyn, in ErbB2-positive breast cancers. Using genetic and pharmacologic approaches, we show that PTB-independent ShcA complexes augment mammary tumorigenesis by increasing the activity of the Src and Fyn tyrosine kinases in an SH2-dependent manner. This bifurcation of signaling complexes from distinct ShcA pools transduces non-redundant signals that integrate the AKT/mTOR and SFK pathways to cooperatively increase breast tumor growth and resistance to tyrosine kinase inhibitors, including lapatinib and PP2. This study mechanistically dissects how the interplay between diverse intracellular ShcA complexes impacts the tyrosine kinome to affect breast tumorigenesis.
Implications: The ShcA adaptor, within distinct signaling complexes, impacts tyrosine kinase signaling, breast tumor growth, and resistance to tyrosine kinase inhibitors. Mol Cancer Res; 16(5); 894–908. ©2018 AACR.
Methylation of the HOXA10 Promoter Directs miR-196b-5p–Dependent Cell Proliferation and Invasion of Gastric Cancer Cells
Authors: Shao Linlin , Chen Zheng , Peng Dunfa , Soutto Mohammed , Zhu Shoumin , Bates Andreia , Zhang Shutian , El-Rifai Wael 
Published: February 2018

Abstract
The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, the regulation and role of miR-196b-5p in gastric cancer was investigated. qRT-PCR demonstrated that miR-196b-5p is significantly overexpressed in human gastric cancer tissues (P &lt; 0.01). In addition, it was determined that HOXA10, a homeobox family member and host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels (P &lt; 0.001). Quantitative pyrosequencing methylation analysis demonstrated significantly lower levels of DNA methylation at the HOXA10 promoter in gastric cancer, as compared with nonneoplastic gastric mucosa specimens. 5-Aza-2′-deoxycytidine treatment confirmed that demethylation of HOXA10 promoter induces the expression of HOXA10 and miR-196b-5p in gastric cancer cell model systems. Using the Tff1 knockout mouse model of gastric neoplasia, hypomethylation and overexpression of HOXA10 and miR-196b-5p in gastric tumors was observed, as compared with normal gastric mucosa from Tff1 wild-type mice. Mechanistically, reconstitution of TFF1 in human gastric cancer cells led to an increased HOXA10 promoter methylation with reduced expression of HOXA10 and miR-196b-5p. Functionally, miR-196b-5p reconstitution promoted human gastric cancer cell proliferation and invasion in vitro. In summary, the current data demonstrate overexpression of miR-196b-5p in gastric cancer and suggest that TFF1 plays an important role in suppressing the expression of miR-196b-5p by mediating DNA methylation of the HOXA10 promoter. Loss of TFF1 expression may promote proliferation and invasion of gastric cancer cells through induction of promoter hypomethylation and expression of the HOXA10/miR-196b-5p axis.
Implications: This study indicates that loss of TFF1 promotes the aberrant overexpression of HOXA10 and miR-196b-5p by demethylation of the HOXA10 promoter, which provides a new perspective of TFF1/HOXA10/miR-196b-5p functions in human gastric cancer. Mol Cancer Res; 16(4); 696–706. ©2018 AACR.
The mTOR Targets 4E-BP1/2 Restrain Tumor Growth and Promote Hypoxia Tolerance in PTEN-driven Prostate Cancer
Authors: Ding Mei , Van der Kwast Theodorus H. , Vellanki Ravi N. , Foltz Warren D. , McKee Trevor D. , Sonenberg Nahum , Pandolfi Pier P. , Koritzinsky Marianne , Wouters Bradly G. 
Published: February 2018

Abstract
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear. Here, even under conditions of aberrant mTOR activation, hypoxia causes dephosphorylation of 4E-BP1/4E-BP2 and increases their association with eIF4E to suppress translation. This is essential for hypoxia tolerance as knockdown of 4E-BP1 and 4E-BP2 decreases proliferation under hypoxia and increases hypoxia-induced cell death. In addition, genetic deletion of 4E-BP1 and 4E-BP2 significantly accelerates all phases of cancer development in the context of PTEN loss–driven prostate cancer in mice despite potent PI3K/AKT and mTOR activation. However, even with a more rapid onset, tumors that establish in the absence of 4E-BP1 and 4E-BP2 have reduced levels of tumor hypoxia and show increased cell death within hypoxic tumor regions. Together, these data demonstrate that 4E-BP1 and 4E-BP2 act as essential metabolic breaks even in the context of aberrant mTOR activation and that they are essential for the creation of hypoxia-tolerant cells in prostate cancer. Mol Cancer Res; 16(4); 682–95. ©2018 AACR.
Incidence and Predictors of Perioperative Complications With Transvenous Lead Extractions
Authors: Sood Nitesh , Martin David T. , Lampert Rachel , Curtis Jeptha P. , Parzynski Craig , Clancy Jude 
Published: February 2018

Background:
Transvenous lead extraction is an integral part of management of patients with cardiovascular implantable electronic devices. Real-world incidence and predictors of perioperative complications in extractions involving implantable cardioverter-defibrillator leads have not been described in detail.

Methods and Results:
Data from the National Cardiovascular Data Registry Implantable Cardioverter-Defibrillator Registry were analyzed. Lead extraction was defined as removal of leads implanted for >1 year. Predictors of major perioperative complications for all extraction procedures (11 304) and for high-voltage lead (8362, 74%), across 762 centers, were analyzed using univariate and multivariate logistic regression. Major complication occurred in 258 (2.3%) extraction procedures. Of these 258 with a complication, 41 (16%) required urgent cardiac surgery. Of these 41, 14 (34%) died during surgery. Among the total 98 (0.9%) deaths reported, 18 (0.16% of total) occurred during transvenous lead extraction. In multivariable logistic regression analysis, female sex, admission other than electively for procedure, ≥3 leads extracted, longer implant duration, dislodgement of other leads, and patient’s clinical status requiring lead extraction (infection/perforation) were associated with increased risk of complications. Smaller lead diameter, flat versus round coil shape, and greater proximal surface coil area were multivariate predictors of major perioperative complications specific to high-voltage leads.

Conclusions:
The rate of major complications and mortality with transvenous lead extraction is similar in the real-world outcomes to that reported in recent single-center studies from high-volume centers. There is significant risk of urgent cardiac surgery, which carries a high mortality, and planning for appropriate cardiothoracic surgery backup is imperative.
Adoption of Sacubitril/Valsartan for the Management of Patients With Heart Failure
Authors: Sangaralingham Lindsey R. , Sangaralingham S. Jeson , Shah Nilay D. , Yao Xiaoxi , Dunlay Shannon M. 
Published: February 2018

Background:
The US Food and Drug Administration approved the use of sacubitril/valsartan in patients with heart failure with reduced ejection fraction in July 2015. We aimed to assess the adoption and prescription drug costs of sacubitril/valsartan in its first 18 months after Food and Drug Administration approval.

Methods and Results:
Using a large US insurance database, we identified privately insured and Medicare Advantage beneficiaries who filled a first prescription for sacubitril/valsartan between July 1, 2015, and December 31, 2016. We compared them to patients treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Outcomes included adoption, prescription drug costs, and 180-day adherence, defined as a proportion of days covered ≥80%. A total of 2244 patients initiated sacubitril/valsartan. Although the number of users increased over time, the proportion of heart failure with reduced ejection fraction patients taking sacubitril/valsartan remained low (<3%). Patients prescribed sacubitril/valsartan were younger, more often male, with less comorbidity than those taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Although a majority of prescription costs were covered by the health plan (mean, $328.37; median, $362.44 per 30-day prescription), out-of-pocket costs were still high (mean, $71.16; median, $40.27). By comparison, median out-of-pocket costs were $2 to $3 for lisinopril, losartan, carvedilol, and spironolactone. Overall, 59.1% of patients were adherent to sacubitril/valsartan. Refill patterns suggested that nearly half of nonadherent patients discontinued sacubitril/valsartan within 180 days of starting.

Conclusions:
Adoption of sacubitril/valsartan after Food and Drug Administration approval has been slow and may be associated with the high cost.
Sutureless Perceval Aortic Valve Versus Conventional Stented Bioprostheses: Meta‐Analysis of Postoperative and Midterm Results in Isolated Aortic Valve Replacement
Authors: Meco Massimo , Montisci Andrea , Miceli Antonio , Panisi Paolo , Donatelli Francesco , Cirri Silvia , Ferrarini Matteo , Lio Antonio , Glauber Mattia 
Published: February 2018

Background
Aortic stenosis is the most common valvular disease and has a dismal prognosis without surgical treatment. The aim of this meta‐analysis was to quantitatively assess the comparative effectiveness of the Perceval (LivaNova) valve versus conventional aortic bioprostheses.

Methods and Results

A total of 6 comparative studies were identified, including 639 and 760 patients who underwent, respectively, aortic valve replacement with the Perceval sutureless valve (P group) and with a conventional bioprosthesis (C group). Aortic cross‐clamping and cardiopulmonary bypass duration were significantly lower in the P group. No difference in postoperative mortality was shown for the P and C groups (2.8% versus 2.7%, respectively; odds ratio [OR]: 0.99 [95% confidence interval (
CI
), 0.52–1.88];
P
=0.98). Incidence of postoperative renal failure was lower in the P group compared with the C group (2.7% versus 5.5%; OR: 0.45 [95%
CI
, 0.25–0.80];
P
=0.007). Incidence of stroke (2.3% versus 1.7%; OR: 1.34 [95%
CI
, 0.56–3.21];
P
=0.51) and paravalvular leak (3.1% versus 1.6%;
OR
: 2.52 [95%
CI
, 0.60–1.06];
P
=0.21) was similar, whereas P group patients received fewer blood transfusions than C group patients (1.16±1.2 versus 2.13±2.2; mean difference: 0.99 [95%
CI
, −1.22 to −0.75];
P
=0.001). The incidence of pacemaker implantation was higher in the P than the C group (7.9% versus 3.1%;
OR
: 2.45 [95%
CI
, 1.44–4.17];
P
=0.001), whereas hemodynamic Perceval performance was better (transvalvular gradient 23.42±1.73 versus 22.8±1.86; mean difference: 0.90 [95%
CI
, 0.62–1.18];
P
=0.001), even during follow‐up (10.98±5.7 versus 13.06±6.2; mean difference: −2.08 [95%
CI
, −3.96 to −0.21];
P
=0.030). We found no difference in 1‐year mortality.

Conclusions
The Perceval bioprosthesis improves the postoperative course compared with conventional bioprostheses and is an option for high‐risk patients.
Sex‐Specific Mechanisms of Resistance Vessel Endothelial Dysfunction Induced by Cardiometabolic Risk Factors
Authors: Davel Ana P. , Lu Qing , Moss M. Elizabeth , Rao Sitara , Anwar Imran J. , DuPont Jennifer J. , Jaffe Iris Z. 
Published: February 2018

Background

The incidence of obesity is rising, particularly among women. Microvascular dysfunction is more common with female sex, obesity, and hyperlipidemia and predicts adverse cardiovascular outcomes, but the molecular mechanisms are unclear. Because obesity is associated with mineralocorticoid receptor (
MR
) activation, we tested the hypothesis that
MR
in endothelial cells contribute to sex differences in resistance vessel dysfunction in response to cardiometabolic risk factors.

Methods and Results

Male and female endothelial cell–specific
MR
knockout mice and
MR
‐intact littermates were randomized to high‐fat‐diet–induced obesity or obesity with hyperlipidemia induced by adeno‐associated virus–based vector targeting transfer of the mutant stable form (DY mutation) of the human
PCSK9
(proprotein convertase subtilisin/kexin type 9) gene and compared with control diet. Female but not male mice were sensitive to obesity‐induced endothelial dysfunction, whereas endothelial function was impaired in obese hyperlipidemic males and females. In males, obesity or hyperlipidemia decreased the nitric oxide component of vasodilation without altering superoxide production or endothelial nitric oxide synthase expression or phosphorylation. Decreased nitric oxide content in obese males was overcome by enhanced endothelium‐derived hyperpolarization–mediated relaxation along with increased
SK
3 expression. Conversely, in females, endothelium‐derived hyperpolarization was significantly impaired by obesity with lower
IK
1 expression and by hyperlipidemia with lower
IK
1 and
SK
3 expression, loss of H
2
O
2
‐mediated vasodilation, and increased superoxide production. Endothelial cell–
MR
deletion prevented endothelial dysfunction induced by risk factors only in females. Rather than restoring endothelium‐derived hyperpolarization in females, endothelial cell–
MR
deletion enhanced nitric oxide and prevented hyperlipidemia‐induced oxidative stress.

Conclusions
These data reveal distinct mechanisms driving resistance vessel dysfunction in males versus females and suggest that personalized treatments are needed to prevent the progression of vascular disease in the setting of obesity, depending on both the sex and the metabolic profile of each patient.
Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1
Authors: Fox Brandon M. , Becker Bryan K. , Loria Analia S. , Hyndman Kelly A. , Jin Chunhua , Clark Hannah , Johns Robin , Yanagisawa Masashi , Pollock David M. , Pollock Jennifer S. 
Published: February 2018

Background

Acute psychosocial stress provokes increases in circulating endothelin‐1 (
ET
‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced
ET
‐1 remain unanswered. We hypothesized that endothelium‐derived
ET
‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.

Methods and Results

Adult male vascular endothelium‐specific
ET
‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (
CSS
), with blood pressure measured by telemetry. An acute pressor response was elicited by
CSS
in both genotypes; however, this response was significantly blunted in vascular endothelium‐specific
ET
‐1 knockout mice compared with control mice that were homozygous for the floxed allele. In mice pretreated for 3 days with the endothelin A antagonist,
ABT
‐627, or the dual endothelin A/B receptor antagonist, A‐182086, the pressor response to
CSS
was similar between genotypes.
CSS
significantly increased plasma
ET
‐1 levels in control mice that were homozygous for the floxed allele.
CSS
failed to elicit an increase in plasma
ET
‐1 in vascular endothelium‐specific
ET
‐1 knockout mice. Telemetry frequency domain analyses suggested similar autonomic responses to stress between genotypes, and isolated resistance arteries demonstrated similar sensitivity to α
1
‐adrenergic receptor‐mediated vasoconstriction.

Conclusions

These findings specify that acute stress‐induced activation of endothelium‐derived
ET
‐1 and subsequent endothelin A receptor activation is a novel mediator of the blood pressure response to acute psychosocial stress.
Gry z czasem, pamięcią i historią: O prozie Milady Součkovej [Games with time, memory and history: About the prose of Milada Součková]
Authors: Woźniak Kamila 
Published: February 2018

Games with time, memory and history: About the prose of Milada SoučkováThe article discusses selected short stories by the Czech avant-garde writer Milada Součková. The author presents a brief interpretation of certain primary themes in the writer’s work, such as the themes of memory and history as a kind of framework of Součková’s writing. Another aspect of the article indicates subjects related to specific historical events that constitute for Součková a backdrop for presenting so-called alternative history which is combined with the microcosm of the characters in her stories. Gry z czasem, pamięcią i historią: O prozie Milady SoučkovejW artykule omówione zostały wybrane opowiadania czeskiej pisarki awangardowej Milady Součkovej. Autorka szkicu przedstawia interpretację stałych motywów w twórczości tej pisarki, takich jak motyw pamięci i historii, jako swoistej klamry ujmującej pisarstwo Součkovej. Kolejnym aspektem artykułu jest wskazanie na funkcjonowanie wątków związanych z konkretnymi wydarzeniami historycznymi, stanowiącymi tło do zaprezentowania tzw. historii alternatywnej, łączącej się z mikroświatem przedstawionych postaci.
Eliminacja lamerstwa. O społecznym użytkowaniu muzyki: Z Adamem Czechem rozmawia Anna Zawadzka [Eliminating cheesiness. The social use of music: Adam Czech interviewed by Anna Zawadzka]
Authors: Zawadzka Anna 
Published: February 2018

Eliminating cheesiness. The social use of music: Adam Czech interviewed by Anna ZawadzkaThe interview with Doctor Adam Czech deals with various forms of distinctions made with the use of music, in the circles of both its authors and recipients. The conversation addresses, among other things, the current status of contemporary classical, folk, and popular music in Poland, and the status of different manners of music consumption. Another issue under discussion concerns the prevailing artistic categories of music evaluations, such as being original and abstract, and the ways of validating and delegitimizing different musical genres. Eliminacja lamerstwa. O społecznym użytkowaniu muzyki: Z Adamem Czechem rozmawia Anna ZawadzkaWywiad z dr. Adamem Czechem dotyczy różnych form dystynkcji dokonywanych za pomocą muzyki zarówno w środowisku jej twórców/twórczyń, jak i odbiorców/odbiorczyń. Przedmiotem rozmowy jest m.in. obecny status muzyki poważnej, muzyki ludowej i muzyki popularnej w Polsce, jak również status poszczególnych sposobów muzycznej konsumpcji, czyli słuchania. Rozmowa dotyczy także dominujących w sztuce kategorii oceniania muzyki, takich jak oryginalność i abstrakcyjność, oraz sposobów uprawomocniania i delegitymizacji poszczególnych gatunków muzycznych.
Wiersze „suchego pogromu” – Marzec ’68 w poezji polskiej (rekonesans) [The poetry of the “dry pogrom” - March 1968 in Polish poetry (a reconnaissance)]
Authors: Kuczyńska-Koschany Katarzyna 
Published: February 2018

The poetry of the “dry pogrom” - March 1968 in Polish poetry (a reconnaissance)The paper construes the distinctive character of March 1968 against the classical definitions of pogroms; hence the selection of Adam Michnik’s phrase “dry pogrom.” It analyzes direct responses to the events, using examples of Aesopian language (Artur Międzyrzecki) and satire (Janusz Szpotański, Natan Tenenbaum), as well as other reactions (Jerzy Ficowski, Aleksander Rymkiewicz). Further, it is concerned with poems from artists affected – to a larger or smaller extent – by the dry pogrom, such as Arnold Słucki. Views from afar – including Kazimierz Wierzyński’s Izrael [Israel] and Jacek Bierezin’s Wygnańcy [Exiles] – have also been analyzed. Michał Głowiński’s formula of “March talk” has been used to interpret the poetics of the poetry about March 1968, with reference to Orwellian Newspeak and Klemperer’s LTI. Finally, in the conclusion, a question is posed of whether the poems of the dry pogrom are a “poetry of dry despair,” a term used by Julia Hartwig to describe Paul Celan’s poems, as they speak about impossible liquids – blood and tears. Wiersze „suchego pogromu” – Marzec ’68 w poezji polskiej (rekonesans)W tekście referuję odrębność pogromu marcowego wobec klasycznych definicji pogromu: dlatego wybieram formułę Adama Michnika „suchy pogrom”. Zajmuję się reakcjami bezpośrednimi; są to przykłady języka „ezopowego” (Artur Międzyrzecki), satyry (Janusz Szpotański, Natan Tenenbaum) i inne (Jerzy Ficowski, Aleksander Rymkiewicz). Interesują mnie także wiersze dotkniętych – w szerszym i węższym sensie – „suchym pogromem” (jak Arnold Słucki). Analizuję widzenie z oddali (np. Kazimierz Wierzyń- ski, Izrael; Jacek Bierezin, Wygnańcy). Wykorzystuję formułę „marcowego gadania” Michała Głowińskiego wobec poetyki wierszy o Marcu ’68 (tu odniesienia do Orwellowskiej nowomowy oraz Klempererowskiej LTI). W zakończeniu pytam, czy wiersze „suchego pogromu” to „poezja suchej rozpaczy” (formuła Julii Hartwig użyta wobec poezji Paula Celana) – o cieczach niemożliwych: krwi i łzach.
Manuskrypt błogosławionej pamięci Pejsacha Bergmana, wedle kopii przekazanej przez syna, Bronisława Bergmana [A manuscript of Pejsach Bergman of blessed memory, according to a copy received from his son, Bronisław Bergman]
Authors: Bergman Pesach , Tokarska-Bakir Joanna 
Published: February 2018

A manuscript of Pejsach Bergman of blessed memory, according to a copy receivedfrom his son, Bronisław BergmanThe text by Pesach Bergman (1898–1944) is an excerpt from his fictionalized memoirs about the life of the shtetl of Widawa from the late 19th century to the 1930s. Written in Yiddish, it was translated into Polish by Dr. Marcin Urynowicz with the assistance of Sara Arm. It constitutes an original and unique literary genre, which is closest to the meditation (Latin: soliloquia), combining elements of social criticism and sentimental recollections. Manuskrypt błogosławionej pamięci Pejsacha Bergmana, wedle kopii przekazanej przez syna, Bronisława BergmanaTekst Pesacha Bergmana (1898–1944) pochodzi z jego fabularyzowanych wspomnień, dotyczących życia sztetlu Widawa w okresie od końca XIX wieku do lat trzydziestych wieku XX. Został zapisany w języku żydowskim, z którego – z pomocą Sary Arm – przełożył go dr Marcin Urynowicz. Ustanawia oryginalny, właściwy tylko sobie gatunek literacki, najbliższy rozmyślaniom (łac. soliloquia), łączącym elementy krytyki społecznej i sentymentalnego wspomnienia.