bluuebunny/crossref_metadata_2025_split huggingface dataset:
Battery operated fan and chronic breathlessness: does it help?
Authors: Barnes-Harris Matilda , Allgar Victoria , Booth Sara , Currow David , Hart Simon , Phillips Jane , Swan Flavia , Johnson Miriam J 
Published: May 2019

ObjectivesTo examine whether use of a hand-held fan (‘fan’) improves breathlessness and increases physical activity.MethodsA secondary exploratory analysis using pooled data from the fan arms of two feasibility randomised controlled trials in people with chronic breathlessness: (1) fan and activity advicevsactivity advice, (2) activity advice alone or with the addition or the ‘calming hand’, or the fan, or both. Descriptive statistics and regression analysis to explore patient characteristics associated with benefit (eg age, sex, diagnosis, general self-efficacy).ResultsForty-one participants were allocated the fan (73 years (IQR 65–76, range 46–88), 59% male, 20 (49%) chronic obstructive pulmonary disease (COPD), three (7%) heart failure, three (7%) cancer). Thirty-five (85%) reported that the fan helped breathing, and 22 (54%) reported increased physical activity.Breathlessness benefit was more likely in older people, those with COPD and those with a carer. However, due to the small sample size none of these findings were statistically significant. Those with COPD were more likely to use the fan than people with other diagnoses (OR 5.94 (95% CI 0.63 to 56.21, p=0.120)).ConclusionsThese exploratory data support that the fan helps chronic breathlessness in most people and adds new data to indicate that the fan is perceived to increase people’s physical activity. There is also a signal of possible particular benefits in people with COPD which is worthy of further study.
On Minrank and Forbidden Subgraphs
Authors: Haviv Ishay 
Published: May 2019

The
minrank
over a field F of a graph
G
on the vertex set { 1,2,… ,
n
} is the minimum possible rank of a matrix
M
∈ F

n
×
n

such that
M

i, i

≠ 0 for every
i
, and
M

i, j

=0 for every distinct non-adjacent vertices
i
and
j
in
G
. For an integer
n
, a graph
H
, and a field F, let
g
(
n
,
H
, F) denote the maximum possible minrank over F of an
n
-vertex graph whose complement contains no copy of
H
. In this article, we study this quantity for various graphs
H
and fields F. For finite fields, we prove by a probabilistic argument a general lower bound on
g
(
n
,
H
,F), which yields a nearly tight bound of Ω (√
n
/ log
n
) for the triangle
H
=
K
3
. For the real field, we prove by an explicit construction that for every non-bipartite graph
H
,
g
(
n
,
H
, R) ≥
n
δ
for some δ = δ (
H
)> 0. As a by-product of this construction, we disprove a conjecture of Codenotti et al. [11]. The results are motivated by questions in information theory, circuit complexity, and geometry.
Alterations in DNA Damage Repair Genes in Primary Liver Cancer
Authors: Lin Jianzhen , Shi Junping , Guo Honglin , Yang Xu , Jiang Yan , Long Junyu , Bai Yi , Wang Dongxu , Yang Xiaobo , Wan Xueshuai , Zhang Lei , Pan Jie , Hu Ke , Guan Mei , Huo Li , Sang Xinting , Wang Kai , Zhao Haitao 
Published: May 2019

Abstract

Purpose:
Alterations in DNA damage repair (DDR) genes produce therapeutic biomarkers. However, the characteristics and significance of DDR alterations remain undefined in primary liver cancer (PLC).

Experimental Design:
Patients diagnosed with PLC were enrolled in the trial (PTHBC, NCT02715089). Tumors and matched blood samples from participants were collected for a targeted next-generation sequencing assay containing exons of 450 cancer-related genes, including 31 DDR genes. The OncoKB knowledge database was used to identify and classify actionable alterations, and therapeutic regimens were determined after discussion by a multidisciplinary tumor board.

Results:
A total of 357 patients with PLC were enrolled, including 214 with hepatocellular carcinoma, 122 with ICC, and 21 with mixed hepatocellular-cholangiocarcinoma. A total of 92 (25.8%) patients had at least one DDR gene mutation, 15 of whom carried germline mutations. The most commonly altered DDR genes were ATM (5%) and BRCA1/2 (4.8%). The occurrence of DDR mutations was significantly correlated with a higher tumor mutation burden regardless of the PLC pathologic subtype. For DDR-mutated PLC, 26.1% (24/92) of patients possessed at least one actionable alteration, and the actionable frequency in DDR wild-type PLC was 18.9% (50/265). Eight patients with the BRCA mutation were treated by olaparib, and patients with BRCA2 germline truncation mutations showed an objective response.

Conclusions:
The landscape of DDR mutations and their association with genetic and clinicopathologic features demonstrated that patients with PLC with altered DDR genes may be rational candidates for precision oncology treatment.
First-in-Human Phase I Study of the Activin A Inhibitor, STM 434, in Patients with Granulosa Cell Ovarian Cancer and Other Advanced Solid Tumors
Authors: Tao Jessica J. , Cangemi Nicholas A. , Makker Vicky , Cadoo Karen A. , Liu Joyce F. , Rasco Drew W. , Navarro Willis H. , Haqq Christopher M. , Hyman David M. 
Published: May 2019

Abstract

Purpose:
STM 434 is a soluble receptor ligand trap targeting activin A, a protein in the TGFβ family that plays important roles in growth, differentiation, and cancer cachexia. This study evaluated the safety, antitumor activity, and metabolic effects of STM 434 in a first-in-human, multicenter, phase I clinical trial (NCT02262455).

Patients and Methods:
Patients with advanced solid tumors were enrolled in 8 dose cohorts ranging from 0.25 mg/kg every 4 weeks to 8 mg/kg every 2 weeks via a 3 + 3 dose-escalation design. The primary endpoint was maximum tolerated dose (MTD). Secondary endpoints included safety, pharmacokinetics, and response. As activin A is implicated in metabolism and muscle function, changes in key metabolic parameters, including lean body mass and 6-minute walk test, were serially measured.

Results:
Thirty-two patients were treated on study. The most common treatment-related adverse events were fatigue (41%) and mucocutaneous bleeding complications including epistaxis (34%) and gingival bleeding (22%), likely related to off-target inhibition of bone morphogenetic protein 9 (BMP9). STM 434 treatment resulted in the expected follicle-stimulating hormone level decreases in most patients and in metabolic parameter changes, including an increase in total lean body mass and 6-minute walk test distance. No responses were observed in the 30 evaluable patients, but the stable disease rate in patients with granulosa cell ovarian cancer was 10 of 12 (80%).

Conclusions:
Although no direct antitumor efficacy was documented, potentially clinically meaningful dose-related metabolic effects, including treatment of cancer cachexia, were observed that support further exploration of activin A inhibitors that limit BMP9 blockade.
See related commentary by Bonilla and Oza, p. 5432
SHP2 Inhibition Overcomes RTK-Mediated Pathway Reactivation in KRAS-Mutant Tumors Treated with MEK Inhibitors
Authors: Lu Hengyu , Liu Chen , Velazquez Roberto , Wang Hongyun , Dunkl Lukas Manuel , Kazic-Legueux Malika , Haberkorn Anne , Billy Eric , Manchado Eusebio , Brachmann Saskia M. , Moody Susan E. , Engelman Jeffrey A. , Hammerman Peter S. , Caponigro Giordano , Mohseni Morvarid , Hao Huai-Xiang 
Published: May 2019

Abstract
FGFR1 was recently shown to be activated as part of a compensatory response to prolonged treatment with the MEK inhibitor trametinib in several KRAS-mutant lung and pancreatic cancer cell lines. We hypothesize that other receptor tyrosine kinases (RTK) are also feedback-activated in this context. Herein, we profile a large panel of KRAS-mutant cancer cell lines for the contribution of RTKs to the feedback activation of phospho-MEK following MEK inhibition, using an SHP2 inhibitor (SHP099) that blocks RAS activation mediated by multiple RTKs. We find that RTK-driven feedback activation widely exists in KRAS-mutant cancer cells, to a less extent in those harboring the G13D variant, and involves several RTKs, including EGFR, FGFR, and MET. We further demonstrate that this pathway feedback activation is mediated through mutant KRAS, at least for the G12C, G12D, and G12V variants, and wild-type KRAS can also contribute significantly to the feedback activation. Finally, SHP099 and MEK inhibitors exhibit combination benefits inhibiting KRAS-mutant cancer cell proliferation in vitro and in vivo. These findings provide a rationale for exploration of combining SHP2 and MAPK pathway inhibitors for treating KRAS-mutant cancers in the clinic.
A Gain-of-Function p53-Mutant Oncogene Promotes Cell Fate Plasticity and Myeloid Leukemia through the Pluripotency Factor FOXH1
Authors: Loizou Evangelia , Banito Ana , Livshits Geulah , Ho Yu-Jui , Koche Richard P. , Sánchez-Rivera Francisco J. , Mayle Allison , Chen Chi-Chao , Kinalis Savvas , Bagger Frederik O. , Kastenhuber Edward R. , Durham Benjamin H. , Lowe Scott W. 
Published: May 2019

Abstract

Mutations in the TP53 tumor suppressor gene are common in many cancer types, including the acute myeloid leukemia (AML) subtype known as complex karyotype AML (CK-AML). Here, we identify a gain-of-function (GOF) Trp53 mutation that accelerates CK-AML initiation beyond p53 loss and, surprisingly, is required for disease maintenance. The Trp53R172H mutation (TP53R175H in humans) exhibits a neomorphic function by promoting aberrant self-renewal in leukemic cells, a phenotype that is present in hematopoietic stem and progenitor cells (HSPC) even prior to their transformation. We identify FOXH1 as a critical mediator of mutant p53 function that binds to and regulates stem cell–associated genes and transcriptional programs. Our results identify a context where mutant p53 acts as a bona fide oncogene that contributes to the pathogenesis of CK-AML and suggests a common biological theme for TP53 GOF in cancer.

Significance:
Our study demonstrates how a GOF p53 mutant can hijack an embryonic transcription factor to promote aberrant self-renewal. In this context, mutant Trp53 functions as an oncogene to both initiate and sustain myeloid leukemia and suggests a potential convergent activity of mutant Trp53 across cancer types.
This article is highlighted in the In This Issue feature, p. 813
Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia
Authors: Paffenholz Pia , Votteler Sinje , Nazari Sassan , Nestler Tim , Salem Johannes , Grabbert Markus , von Brandenstein Melanie , Loosen Sven H. , Zey Silke , Heidenreich Axel , Herden Jan , Denil Johan 
Published: May 2019

<b><i>Background:</i></b> The oestrogen antagonist tamoxifen has been suggested as an empiric treatment option for treating idiopathic oligoathenoteratozoospermia (iOAT). <b><i>Objectives:</i></b> To analyse the use of tamoxifen in iOAT. <b><i>Method:</i></b> Fifty-seven men receiving tamoxifen for iOAT were recruited from 2016 to 2017 in a retrospective, single-centre setting. Hormone and semen analysis was performed before and after 3 months of treatment. <b><i>Results:</i></b> After a 3-month treatment, serum levels of testosterone (3.4 ng/mL [2.7–4.8] vs. 5.3 [3.1–7.1]; <i>p</i> = 0.026), follicle stimulating hormone (FSH; 7.6 [5.9–11.5] vs. 15.9 mIU/mL [8.4–19.9]; <i>p</i> = 0.003) and luteinizing hormone (4.5 [3.3–6.6] vs. 7.6 mIU/mL [4.8–10.7]; <i>p</i> = 0.007) significantly increased. At a cut-off of &#x3e;8.8 mIU/mL, serum levels of FSH were predictive for an improved sperm motility (OR 0.229 [95% CI 0.068–0.773]; <i>p</i> = 0.018) and serum levels of inhibin B were predictive for an improved total sperm count at a cut-off of &#x3c;82 ng/L (OR 18.0 [95% CI 1.267–255.744]; <i>p</i> = 0.033). During an 11 month-follow-up, patients receiving tamoxifen showed a clinical pregnancy rate of 42%, leading to a live birth rate of 56% of all pregnant women. Twenty-three per cent of all patients reported non-serious adverse events. <b><i>Conclusions:</i></b> Tamoxifen is effective in improving the total sperm count as well as motility and can thus be safely used as empiric medical therapy in iOAT.
АНАЛІТИЧНІ АСПЕКТИ МІЖЛАБОРАТОРНОГО КОНТРОЛЮ ЯКОСТІ РЕЗУЛЬТАТІВ ЕЛЕМЕНТНОГО АНАЛІЗУ В БІОЛОГІЧНИХ СЕРЕДОВИЩАХ ЛЮДИНИ
Authors: Andrushyshyna I. N. , Golub I. O. , Lampeka O. G. 
Published: May 2019

Вступ. У роботі розглянуто питання аналізу мікроелементного складу сироватки і цільної крові людини як важливий момент проведення клінічної діагностики. Стандартні зразки біологічних матеріалів є повноцінним носієм правильності та прецесійності вимірювання.
Мета дослідження – дати порівняльну оцінку правильності та прецесійності визначення макро- і мікроелементів у тестовій сироватці й цільній крові методом багатоелементного аналізу оптико-емісійної спектрометрії з індуктивно зв’язаною плазмою.
Методи дослідження. Зразки сироватки крові на вміст Na, K, Ca, Mg, Fe, Cu, Zn, P та цільної крові на вміст Pb, Cd, Mn, Se готували відповідно до валідованої і затвердженої методики. Дослідження проводили на приладі оптико-емісійної спектрометрії з індуктивно зв’язаною плазмою моделі Optima 2100 DV фірми “Perkin-Elmer” (США).
Результати й обговорення. Дослідження по визначення 8-ми хімічних елементів у сироватці крові за програмою “Sequas” (FORTRESS), які проводили впродовж року, продемонстрували високу кількість добрих (6) та задовільних (4) результатів з 12-ти визначень. Найбільша кількість високих збігів під час участі в програмі “LAMP” (CDC) була характерна для Mn і Se, менша – для Cd та Pb. Визначено методологічні підходи для отримання адекватних результатів, наприклад застосування коефіцієнта поправок та прийоми корекції спектральних завад. Описано особливості використання референтних зразків для проведення міжлабораторних тестів і контролю якості досліджень вмісту макро- та мікроелементів у біологічних середовищах. Показано перспективність застосування сучасних спектральних методів багатоелементного аналізу в клінічній діагностиці мікроелементозів.
Висновки. Участь у програмах міжлабораторних порівнянь макро- та мікроелементів дозволяє вдосконалювати власні внутрішні процедури контролю якості визначення у біологічних середовищах, дає додаткову зовнішню оцінку випробувальних спроможностей лабораторій і, таким чином, підвищує надійність отриманих результатів лабораторної діагностики.
Cloud Radiative Feedbacks and El Niño–Southern Oscillation
Authors: Middlemas Eleanor A. , Clement Amy C. , Medeiros Brian , Kirtman Ben 
Published: May 2019

Abstract
Cloud radiative feedbacks are disabled via “cloud-locking” in the Community Earth System Model, version 1.2 (CESM1.2), to result in a shift in El Niño–Southern Oscillation (ENSO) periodicity from 2–7 years to decadal time scales. We hypothesize that cloud radiative feedbacks may impact the periodicity in three ways: by 1) modulating heat flux locally into the equatorial Pacific subsurface through negative shortwave cloud feedback on sea surface temperature anomalies (SSTA), 2) damping the persistence of subtropical southeast Pacific SSTA such that the South Pacific meridional mode impacts the duration of ENSO events, or 3) controlling the meridional width of off-equatorial westerly winds, which impacts the periodicity of ENSO by initiating longer Rossby waves. The result of cloud-locking in CESM1.2 contrasts that of another study, which found that cloud-locking in a different global climate model led to decreased ENSO magnitude across all time scales due to a lack of positive longwave feedback on the anomalous Walker circulation. CESM1.2 contains this positive longwave feedback on the anomalous Walker circulation, but either its influence on the surface is decoupled from ocean dynamics or the feedback is only active on interannual time scales. The roles of cloud radiative feedbacks in ENSO in other global climate models are additionally considered. In particular, it is shown that one cannot predict the role of cloud radiative feedbacks in ENSO through a multimodel diagnostic analysis. Instead, they must be directly altered.
Rainfall Estimation Accuracy of a Nationwide Instantaneously Sampling Commercial Microwave Link Network: Error Dependency on Known Characteristics
Authors: de Vos L. W. , Overeem A. , Leijnse H. , Uijlenhoet R. 
Published: May 2019

AbstractCommercial microwave links are installed and maintained for the purpose of telecommunication. Hydrometeors between transmitting and receiving antennas cause the microwave signal to be attenuated. From signal attenuation, the path-averaged rainfall intensity can be calculated. A 7-month dataset of instantaneously logged signal powers from almost 2000 unique links in the Netherlands is analyzed. Rainfall intensities are calculated with the RAINLINK package with a novel preprocessing module, enabling the package to be applied on instantaneously logged data from now on. Rainfall intensities per link are validated with the path-averaged rainfall intensities according to a gauge-adjusted radar product. Both the overall performance and the dependence of errors on link characteristics and measurement conditions are evaluated. The coefficient of variation decreases from 3.70 to 2.32 and the correlation increases from 0.30 to 0.63 from instantaneous to daily estimates of rainfall accumulations. The coefficient of variation is also smaller during heavy rainfall. Errors are largest for pathlengths shorter than 2 km, for observations during the late night and early morning, and for observations during colder months (when solid or melting precipitation could occur and dew is more likely to form on the antennas). Comparison of our results with those of earlier studies shows that minimum/maximum sampling (widely employed in network management systems) outperforms instantaneous sampling regarding detection of both quantity and occurrence of rain at a 15-min sampling rate in the Dutch climate.
Precipitation Enhancement via the Interplay between Atmospheric Rivers and Cutoff Lows
Authors: Tsuji Hiroki , Takayabu Yukari N. 
Published: May 2019

Abstract
A significant enhancement of precipitation can result from the interplay between two independent, large-scale phenomena: an atmospheric river (AR) and a cutoff low. An AR is a long, narrow region with a deep moist layer. A cutoff low is an upper-level cyclonic eddy isolated from the meandering upper-level westerly jet. Herein, we construct composites of cutoff lows both close to an AR (AR-close category) and distant from an AR (AR-distant category) over a 14-yr period across the western North Pacific region. A comparison between the two categories shows an enhanced precipitation area to the northwest of the cutoff low and to the south of the AR axis in the AR-close category. The horizontal formation among the AR, cutoff low, and enhanced precipitation area in the composite coincides with that in a disastrous flood event that occurred in Hiroshima, Japan, in 2014. The deep moist layer associated with the AR, and the destabilization and isentropic up-gliding effect associated with the cutoff low are also observed in both the composite and the Hiroshima cases. We further evaluate the distribution of quasigeostrophic forcing (Q vector) for vertical motion. This shows that warm air advection associated with the AR overcomes the descending forcing inherent in the northwest of the cutoff low and makes the instability and up-gliding effect in that region more effective. These results indicate that the interplay between ARs and cutoff lows is a common mechanism in the enhancement of precipitation and the Hiroshima case is an extreme precipitation event caused by this interplay.
Feasibility of a traditional and teletreatment approach to mirror therapy in patients with phantom limb pain: a process evaluation performed alongside a randomized controlled trial
Authors: Rothgangel Andreas , Braun Susy , Smeets Rob , Beurskens Anna 
Published: May 2019

Objective: To evaluate the delivery, acceptance and experiences regarding a traditional and teletreatment approach to mirror therapy as delivered in a randomized controlled trial. Design: Mixed methods, prospective study. Setting: Rehabilitation centres, hospital and private practices. Subjects: Adult patients with phantom pain following lower limb amputation and their treating physical and occupational therapists. Interventions: All patients received 4 weeks of traditional mirror therapy ( n = 51), followed by 6 weeks of teletreatment ( n = 26) or 6 weeks of self-delivered mirror therapy ( n = 25). Main measures: Patient files, therapist logs, log files teletreatment, acceptance questionnaire and interviews with patients and their therapists. Results: In all, 51 patients and 10 therapists participated in the process evaluation. Only 16 patients (31%) received traditional mirror therapy according to the clinical framework during the first 4 weeks. Between weeks 5 and 10, the teletreatment was used by 14 patients (56%) with sufficient dose. Teletreatment usage decreased from a median number of 31 (weeks 5–10) to 19 sessions (weeks 11–24). Satisfactory teletreatment user acceptance rates were found with patients demonstrating higher scores (e.g. regarding the usefulness to control pain) than therapists. Potential barriers for implementation of the teletreatment perceived by patients and therapists were related to insufficient training and support as well as the frequency of technical problems. Conclusion: Traditional mirror therapy and the teletreatment were not delivered as intended in the majority of patients. Implementation of the teletreatment in daily routines was challenging, and more research is needed to evaluate user characteristics that influence adherence and how technology features can be optimized to develop tailored implementation strategies.
Toutes ces fois où je me suis trouvé au milieu (tentative d’autoportrait)
Authors: Farah Alain 
Published: May 2019

J’ai appris l’existence de Dante Alighieri en écoutant un fichier mp3. Il y a une quinzaine d’années, je traînais souvent sur Ubuweb, le site du poète américain Kenneth Goldsmith. C’était (et c’est encore) un véritable coffre au trésor pour quiconque s’intéresse aux pratiques poétiques d’avant-garde et à la littérature en général. Le cours de Roland Barthes intitulé La préparation du roman s’y trouvait (et s’y trouve encore). Je l’ai téléchargé. Dante est entré dans ma vie.
A cognitive occupation-based programme for people with multiple sclerosis: A new occupational therapy cognitive rehabilitation intervention
Authors: Hynes Sinéad M , Forwell Susan 
Published: May 2019

Introduction Cognitive difficulties have been reported to have the greatest effect on function and quality of life in people with multiple sclerosis, affecting 50–60% of people. To date, few interventions have been developed to treat cognitive issues in multiple sclerosis. Here we report on a Cognitive Occupation-Based programme (COB-MS) for people with Multiple Sclerosis an evidence-based intervention to address everyday problems encountered due to cognitive difficulties. The aim of this research was to explore the views of people with multiple sclerosis and occupational therapists on the programme and its potential implementation in practice. Methods Data were elicited from a purposive sample of 12 people from two stakeholder groups, people with multiple sclerosis (n = 5) and occupational therapists (n = 7), through focus groups and interviews. The programme and related materials were presented, and contributions recorded, transcribed and thematically analysed. Results Two main themes were identified from analysis of the data: response to the intervention and challenges to implementing the programme. Occupational therapists agreed that the COB-MS is client-centred. People with multiple sclerosis thought that it was a validating intervention. The overall format was viewed to be useful and feasible. Conclusion The COB-MS for people with Multiple Sclerosis is the first known cognitive intervention using an occupation frame of reference to address difficulties faced among persons with multiple sclerosis and was found to be timely and relevant to the needs of the population.