bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression
Authors: Godse Neal R. , Khan Nayel , Yochum Zachary A. , Gomez-Casal Roberto , Kemp Carolyn , Shiwarski Daniel J. , Seethala Raja S. , Kulich Scott , Seshadri Mukund , Burns Timothy F. , Duvvuri Umamaheswar 
Published: September 2017

Abstract
Purpose: TMEM16A is a calcium-activated chloride channel that is amplified in a variety of cancers, including 30% of head and neck squamous cell carcinomas (HNSCCs), raising the possibility of an anti-apoptotic role in malignant cells. This study investigated this using a multimodal, translational investigation.
Experimental Design: Combination of (i) in vitro HNSCC cell culture experiments assessing cell viability, apoptotic activation, and protein expression (ii) in vivo studies assessing similar outcomes, and (iii) molecular and staining analysis of human HNSCC samples.
Results: TMEM16A expression was found to correlate with greater tumor size, increased Erk 1/2 activity, less Bim expression, and less apoptotic activity overall in human HNSCC. These findings were corroborated in subsequent in vitro and in vivo studies and expanded to include a cisplatin-resistant phenotype with TMEM16A overexpression. A cohort of 41 patients with laryngeal cancer demonstrated that cases that recurred after chemoradiation failure were associated with a greater TMEM16A overexpression rate than HNSCC that did not recur.
Conclusions: Ultimately, this study implicates TMEM16A as a contributor to tumor progression by limiting apoptosis and as a potential biomarker of more aggressive disease. Clin Cancer Res; 23(23); 7324–32. ©2017 AACR.
A Unified Approach to Targeting the Lysosome's Degradative and Growth Signaling Roles
Authors: Rebecca Vito W. , Nicastri Michael C. , McLaughlin Noel , Fennelly Colin , McAfee Quentin , Ronghe Amruta , Nofal Michel , Lim Chun-Yan , Witze Eric , Chude Cynthia I. , Zhang Gao , Alicea Gretchen M. , Piao Shengfu , Murugan Sengottuvelan , Ojha Rani , Levi Samuel M. , Wei Zhi , Barber-Rotenberg Julie S. , Murphy Maureen E. , Mills Gordon B. , Lu Yiling , Rabinowitz Joshua , Marmorstein Ronen , Liu Qin , Liu Shujing , Xu Xiaowei , Herlyn Meenhard , Zoncu Roberto , Brady Donita C. , Speicher David W. , Winkler Jeffrey D. , Amaravadi Ravi K. 
Published: September 2017

Abstract
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e., autophagy and macropinocytosis) while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQ) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy. Central nitrogen methylation of the DQ linker enhances lysosomal localization and potency. An in situ photoaffinity pulldown identified palmitoyl-protein thioesterase 1 (PPT1) as the molecular target of DQ661. PPT1 inhibition concurrently impairs mTOR and lysosomal catabolism through the rapid accumulation of palmitoylated proteins. DQ661 inhibits the in vivo tumor growth of melanoma, pancreatic cancer, and colorectal cancer mouse models and can be safely combined with chemotherapy. Thus, lysosome-directed PPT1 inhibitors represent a new approach to concurrently targeting mTORC1 and lysosomal catabolism in cancer.
Significance: This study identifies chemical features of dimeric compounds that increase their lysosomal specificity, and a new molecular target for these compounds, reclassifying these compounds as targeted therapies. Targeting PPT1 blocks mTOR signaling in a manner distinct from catalytic inhibitors, while concurrently inhibiting autophagy, thereby providing a new strategy for cancer therapy. Cancer Discov; 7(11); 1266–83. ©2017 AACR.
See related commentary by Towers and Thorburn, p. 1218.
This article is highlighted in the In This Issue feature, p. 1201
A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with PD1-Blocking Agents for Metastatic Melanoma
Authors: Pföhler Claudia , Eichler Hermann , Burgard Barbara , Krecké Nathalie , Müller Cornelia S.L. , Vogt Thomas 
Published: September 2017

<b>Background: </b>Checkpoint blocking agents such as pembrolizumab or nivolumab may induce a diversity of mostly autoimmune-mediated side effects. These autoimmune phenomena mainly affect ductless glands such as the pituitary gland (hypophysitis), the thyroid gland (thyreoiditis), the skin (vitiligo and rash), the colon (colitis), and the lung (pneumonitis). Furthermore, many other organs or organ systems may be affected. <b>Case Report: </b>This work describes a case of an immune thrombocytopenia that developed or rather became clinically significant shortly after initiation of a systemic therapy with first nivolumab and later pembrolizumab given due to metastatic melanoma. Platelet counts before this systemic therapy were slightly decreased with values around 110/nl (normal value 140-400/nl). Thrombocytopenia developed or became apparent rapidly within 10 days after the first intravenous application of nivolumab and worsened after changeover to pembrolizumab. Therapy had to be stopped due to disease progression and steady aggravation of thrombocytopenia. Immune hematology assays could prove an autoimmune mediated genesis of thrombocytopenia. <b>Conclusion: </b>Checkpoint inhibitors may induce a multiplicity of mostly autoimmune-mediated side effects. In contrast to chemotherapy-induced cytopenia that results from bone marrow toxicity, thrombocytopenia in melanoma patients treated with checkpoint inhibiting substances seems to result from autoimmune-mediated side effects in the majority of the cases. Thorough laboratory controls during these therapies are therefore required. In case of thrombocytopenia, immune hematology testing to diagnose or rule out immune thrombocytopenia is indispensable.
Impact of Incident Heart Failure on Body Composition Over Time in the Health, Aging, and Body Composition Study Population
Authors: Forman Daniel E. , Santanasto Adam J. , Boudreau Robert , Harris Tamara , Kanaya Alka M. , Satterfield Suzanne , Simonsick Eleanor M. , Butler Javed , Kizer Jorge R. , Newman Anne B. 
Published: September 2017

Background:
Prevalence of heart failure (HF) increases significantly with age, coinciding with age-related changes in body composition that are common and consequential. Still, body composition is rarely factored in routine HF care.

Methods and Results:

The Health, Aging, and Body Composition study is a prospective cohort study of nondisabled adults. Using yearly dual-energy x-ray absorptiometry, body composition was assessed in the Health, Aging, and Body Composition study over 6 years, comparing those who developed incident HF versus those who did not. Among 2815 Health, Aging, and Body Composition participants (48.5% men; 59.6% whites; mean age, 73.6±2.9 years), 111 developed incident HF over the 6-year study period. At entry into the Health, Aging, and Body Composition study, men and women who later developed HF had higher total body mass when compared with those versus those who did not develop HF (men, 80.9±10 versus 78.6±12.9 kg,
P
=0.05; women, 72.7±15.0 versus 68.2±14.2 kg,
P
=0.01, respectively). However, after developing HF, loss of total lean body mass was disproportionate; men with HF lost 654.6 versus 391.4 g/y in non-HF participants,
P
=0.02. Loss of appendicular lean mass was also greater with HF (−419.9 versus −318.2 g/y;
P
=0.02), even after accounting for total weight change. Among women with HF, loss of total and appendicular lean mass were also greater than in non-HF participants but not to the extent seen among men.

Conclusions:
Incident HF in older adults was associated with disproportionate loss of lean mass, particularly among men. Prognostic implications are significant, with key sex-specific inferences on physical function, frailty, disability, and pharmacodynamics that all merit further investigation.
Biomechanical and Hemodynamic Measures of Right Ventricular Diastolic Function: Translating Tissue Biomechanics to Clinical Relevance
Authors: Jang Sae , Vanderpool Rebecca R. , Avazmohammadi Reza , Lapshin Eugene , Bachman Timothy N. , Sacks Michael , Simon Marc A. 
Published: September 2017

Background

Right ventricular (
RV
) diastolic function has been associated with outcomes for patients with pulmonary hypertension; however, the relationship between biomechanics and hemodynamics in the right ventricle has not been studied.

Methods and Results

Rat models of
RV
pressure overload were obtained via pulmonary artery banding (
PAB
; control, n=7;
PAB,
n=5). At 3 weeks after banding,
RV
hemodynamics were measured using a conductance catheter. Biaxial mechanical properties of the
RV
free wall myocardium were obtained to extrapolate longitudinal and circumferential elastic modulus in low and high strain regions (E
1
and E
2
, respectively). Hemodynamic analysis revealed significantly increased end‐diastolic elastance (E
ed
) in
PAB
(control: 55.1 mm Hg/mL [interquartile range: 44.7–85.4 mm Hg/mL];
PAB
: 146.6 mm Hg/mL [interquartile range: 105.8–155.0 mm Hg/mL];
P
=0.010). Longitudinal E
1
was increased in
PAB
(control: 7.2 kPa [interquartile range: 6.7–18.1 kPa];
PAB
: 34.2 kPa [interquartile range: 18.1–44.6 kPa];
P
=0.018), whereas there were no significant changes in longitudinal E
2
or circumferential E
1
and E
2
. Last, wall stress was calculated from hemodynamic data by modeling the right ventricle as a sphere:

stress
=

Pressure
×
radius

2
×
thickness

.

Conclusions

RV
pressure overload in
PAB
rats resulted in an increase in diastolic myocardial stiffness reflected both hemodynamically, by an increase in E
ed
, and biomechanically, by an increase in longitudinal E
1
. Modest increases in tissue biomechanical stiffness are associated with large increases in E
ed
. Hemodynamic measurements of
RV
diastolic function can be used to predict biomechanical changes in the myocardium.
The Conflict between Sovereign Immunity and the Cargo of Sunken Colonial Vessels
Authors: Losier M.M. 
Published: September 2017

Abstract
Cloaking the cargo of sunken colonial vessels with flag State immunity creates pro tempore resolutions through procedural impediments that inevitably reward illegal acts, revitalize colonial policies and extend periods of unjust enrichment. Immunity should only be extended when conventional law requirements are met and applied in conformity with any rules applicable between the parties in light of present-day conditions. Absent immunity, States with verifiable links could argue merit-based claims in unbiased fora that could rely on modern legal principles, rather than those prevailing when the cargo sank, to adjudicate contemporary disputes. Merit-based resolutions would address the Pandora’s box resulting from the convergence of advances in underwater technologies and the socio-political shifts that occurred since the cargo sank. Historically inert pauses under water unique to other legal quagmires offer an inimitable opportunity, when immunity is restricted, to adhere to modern ethical principles and to halt the lingering effects of condemned regimes.
Borrowings But No Diffusion: A Case of Language Contact in the Lake Chad Basin
Authors: Allison Sean 
Published: September 2017

Makary Kotoko, a Chadic language spoken in the flood plain directly south of Lake Chad in Cameroon, has an estimated 16,000 speakers. An analysis of a lexical database for the language shows that of the 3000 or so distinct lexical entries in the database, almost 1/3 (916 items) have been identified as borrowed from other languages in the region. The majority of the borrowings come from Kanuri, a Nilo-Saharan language of Nigeria, with an estimated number of speakers ranging from 1 to 4 million. In this article I first present the number of borrowings specifically from Kanuri relative to the total number of borrowed items in Makary Kotoko, and the lexical/grammatical categories in Makary Kotoko that have incorporated Kanuri borrowings. I follow this by presenting the linguistic evidence which not only suggests a possible time frame for when the borrowings from Kanuri came into Makary Kotoko, but also supports the idea that this is essentially a case of completed language contact. After discussing the lexical and grammatical borrowings from Kanuri into Makary Kotoko in detail, I explore the limited evidence in Makary Kotoko for lexical and grammatical ‘calquing’ from Kanuri, resulting in almost no structural diffusion from Kanuri into Makary Kotoko. I finish with a few proposals as to why this is the case in this instance of language contact in the Lake Chad basin.
Enchelycore propinqua sp. nov., a new moray eel (Anguilliformes: Muraenidae: Muraeninae) from the Indian Coast
Authors: MOHAPATRA ANIL , SMITH DAVID G. , MOHANTY SWARUP RANJAN , MISHRA SUBHRENDU SEKHAR , TUDU PRASAD C. 
Published: September 2017

A new moray Enchelycore propinqua sp. nov., is described from a single specimen collected from Visakhapatnam fishing harbour, Andhra Pradesh, India. The species has a reddish brown body mottled with irregular creamy white spots; dorsal-fin origin considerably behind gill opening, but well ahead of level of anus; sharply pointed recurved teeth; biserial intermaxillary and maxillary teeth, those of inner row larger and more widely spaced than outer row. It differs from congeners by higher predorsal vertebrae and lower total vertebral count (MVF 20-51-120). The colouration is distinctly different from other species of the genus.
Relationship between serum 25-hydroxy vitamin D levels and retinopathy of prematurity
Authors: Kabataş Emrah Utku , Dinlen Nurdan Fettah , Zenciroğlu Ayşegül , Dilli Dilek , Beken Serdar , Okumuş Nurullah 
Published: September 2017

Aim To evaluate the relationship between serum 25-hydroxy vitamin D, 25 (OH) D, levels and retinopathy of prematurity. Methods and Results Serum 25 (OH) D levels were measured in 97 very low birth weight infants, prior to vitamin D supplementation. The development of retinopathy of prematurity and its treatment requirement were evaluated. At follow-up, retinopathy of prematurity developed in 71 (73.2%) infants. Serum 25 (OH) D levels were significantly lower in infants with retinopathy of prematurity than ones without retinopathy of prematurity ( P < 0.001). The infants who required treatment had lower 25 (OH) D levels compared with the infants who did not required treatment (7.1 ± 5.2 ng/ml vs. 11.9 ± 6.5 ng/ml; P = 0.003). Multivariate analysis showed that lower serum 25 (OH) D levels may be a risk factor for retinopathy of prematurity development [OR: 1.14, 95% CI (1.02–1.27), P = 0.02]. Conclusion Lower 25 (OH) D levels in the first days of life may be related to retinopathy of prematurity development and treatment requirement in premature infants.
Impact of region of interest (ROI) size on the diagnostic performance of shear wave elastography in differentiating solid breast lesions
Authors: Moon Jin Hee , Hwang Ji-Young , Park Jeong Seon , Koh Sung Hye , Park Sun-Young 
Published: September 2017

Background Shear wave elastography (SWE) using a region of interest (ROI) can demonstrate the quantitative elasticity of breast lesions. Purpose To prospectively evaluate the impact of two different ROI sizes on the diagnostic performance of SWE for differentiating benign and malignant breast lesions. Material and Methods A total of 154 breast lesions were included. Two types of ROIs were investigated: one involving an approximately 2-mm diameter, small round ROIs placed over the stiffest area of the lesion, as determined by SWE (ROI-S); and another ROI drawn along the margin of the lesion using a touch pen or track ball to encompass the entire lesion (ROI-M). Maximum elasticity (Emax), mean elasticity (Emean), minimum elasticity (Emin), and standard deviation (SD) were measured for the two ROIs. The area under the receiver operating characteristic curve (AUC) as well as the sensitivity and specificity of each elasticity value were determined. Results The AUCs for ROI-S were higher than those for ROI-M when differentiating benign and malignant breast solid lesions. The Emax, Emean, Emin, and SD of the elasticity values for ROI-S were 0.865, 0.857, 0.816, and 0.849, respectively, and for ROI-M were 0.820, 0.780, 0.724, and 0.837, respectively. However, only Emax ( P = 0.0024) and Emean ( P = 0.0015) showed statistically significant differences. For ROI-S, the sensitivity and specificity of Emax were 78.8% and 84.3%, respectively, and those for Emean were 80.8% and 81.4%, respectively. Conclusion Using ROI-S with Emax and Emean has better diagnostic performance than ROI-M for differentiating between benign and malignant breast lesions.
Non-invasive vagus nerve stimulation for the management of refractory primary chronic headaches: A real-world experience
Authors: Trimboli Michele , Al-Kaisy Adnan , Andreou Anna P , Murphy Madeleine , Lambru Giorgio 
Published: September 2017

Background Non-invasive vagus nerve stimulation has initial evidence of efficacy in migraine and cluster headache. However, little is known about its role in the management of refractory chronic headaches. Methods We evaluated the preventive and abortive effects of non-invasive vagus nerve stimulation in 41 consecutive patients with refractory primary chronic headaches in an open-label prospective clinical audit. Headache diaries were used to collect clinical information. Those who obtained at least 30% reduction in headache days/episodes after three months of treatment were considered responders and were offered treatment continuation. Results Twenty-three patients with chronic migraine, 12 with chronic cluster headache, four with hemicrania continua and two with short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA) were treated. Two of 23 chronic migraine patients, one of 12 chronic cluster headache patients, and two of four hemicrania continua patients were considered responders. None of the patients with SUNA benefited from the therapy. Two chronic migraine patients were able to reduce the pain severity of moderate migraines with non-invasive vagus nerve stimulation. Conclusion Non-invasive vagus nerve stimulation may not constitute an effective acute nor preventive treatment in refractory chronic primary headaches. The encouraging effect in hemicrania continua warrants further evaluation in larger studies.
Characterizing Citizens’ Preferences for Engagement in Patient Care and Research in Adult and Pediatric Intensive Care Units
Authors: Burns Karen E. A. , Rizvi Leena , Charteris Anna , Laskey Samuel , Bhatti Saima B. , Chokar Kamalprit , Choong Karen L. M. 
Published: September 2017

Rationale: Engagement promotes and supports the active participation of patients and families in health care and research to strengthen their influence on decision-making. We sought to characterize how citizens wish to be engaged in care and research in the intensive care unit (ICU). Methods: Interviewers administered questionnaires to visitors in 3 adult ICUs and 1 pediatric ICU. Results: We surveyed 202 (adult [n = 130] and pediatric [n = 72]) visitors. Adults and pediatric visitors prioritized 3 patient care topics (family involvement in rounds, improving communication between family members and health-care providers, and information transmission between health-care practitioners during patient transfers) and 2 research topics (evaluating prevention and recovery from critical illness). Preferred engagement activities included sharing personal experiences, identifying important topics and outcomes, and finding ways to make changes that respected their needs. Both respondent groups preferred to participate by completing electronic surveys or comment cards and answering questions on a website. Few respondents (<5%) wanted to participate in committees that met regularly. Although adult and pediatric respondents identified common facilitators and barriers to participation, they ranked them differently. Although both groups perceived engagement to be highly important, adult respondents were significantly less confident that their participation would impact care (7.6 ± 2.2 vs 8.3 ± 1.8; P = .01) and research (7.3 ± 2.4 vs 8.2 ± 2.0; P = .01) and were significantly less willing to participate in care (5.6 ± 2.9 vs 6.7 ± 3.0; P = .007) and research (4.7 ± 3.0 vs ± 5.8 ± 3.0; P = .02). Conclusions: Adult and pediatric visitors expressed comparable engagement preferences, identified similar facilitators and barriers, and rated engagement highly. Adult visitors were significantly less confident that their participation would be impactful and were significantly less willing to engage in care and research.
Medication management strategies used by older adults with heart failure: A systems-based analysis
Authors: Mickelson Robin S , Holden Richard J 
Published: September 2017

Background: Older adults with heart failure use strategies to cope with the constraining barriers impeding medication management. Strategies are behavioral adaptations that allow goal achievement despite these constraining conditions. When strategies do not exist, are ineffective or maladaptive, medication performance and health outcomes are at risk. While constraints to medication adherence are described in literature, strategies used by patients to manage medications are less well-described or understood. Aim: Guided by cognitive engineering concepts, the aim of this study was to describe and analyze the strategies used by older adults with heart failure to achieve their medication management goals. Methods: This mixed methods study employed an empirical strategies analysis method to elicit medication management strategies used by older adults with heart failure. Observation and interview data collected from 61 older adults with heart failure and 31 caregivers were analyzed using qualitative content analysis to derive categories, patterns and themes within and across cases. Results: Data derived thematic sub-categories described planned and ad hoc methods of strategic adaptations. Stable strategies proactively adjusted the medication management process, environment, or the patients themselves. Patients applied situational strategies (planned or ad hoc) to irregular or unexpected situations. Medication non-adherence was a strategy employed when life goals conflicted with medication adherence. The health system was a source of constraints without providing commensurate strategies. Conclusions: Patients strived to control their medication system and achieve goals using adaptive strategies. Future patient self-mangement research can benefit from methods and theories used to study professional work, such as strategies analysis.