bluuebunny/crossref_metadata_2025_split huggingface dataset:
Police involvement, characteristics and outcomes of place of safety referrals in the Scottish Highlands
Authors: Simpson Struan , Eze Jude 
Published: February 2020

Aims and methodTo characterise police involvement with those detained under place of safety legislation and determine factors associated with admission to hospital. Place of safety referrals over a 1-year period were identified retrospectively and evaluated.ResultsPlace of safety legislation is generally used with regard to concerns about suicide. Individuals are often removed from high-risk areas and referrals to police are frequently initiated by individuals themselves. A diagnosis of mental illness or personality disorder predicted hospital admission. Presence of senior nursing staff at assessment, but not the seniority of the doctor, was associated with discharge.Clinical implicationsCloser multiagency working is required as police are currently being recruited to fill a void between mental health services and the population they serve. Junior doctors require more senior support in making complex, and often risky, emergency management decisions with this population.
Reviewing the burden of comorbidity in patients receiving specialist in-patient treatment for drug and alcohol problems
Authors: Bradley Alice , Martin Amy 
Published: February 2020

Aims and methodTo compare and contrast the burden of comorbidity in a population receiving in-patient treatment for substance misuse with that of a cohort admitted to the same unit 4 years previously. The Charlson Comorbidity Index (CCI) was used to quantify patients' comorbidity and predict 10-year survival.ResultsThere was a marked reduction in predicted 10-year survival: in 2014, 22% of patients had a predicted 98% chance of 10-year survival, whereas only 2% in the 2018 cohort had a predicted 98% chance. Additionally, in 2014 only 9% of patients had a <20% 10-year predicted survival chance, whereas 28% in 2018 had a predicted 10-year survival chance of <20%. In this time, funding for services was cut by 23% and the 12-bed unit was reduced to 8 beds. This resulted in an increase in the average waiting time from 30 to 65 days. In 2018, more patients were admitted for alcohol detoxification, rising from 79% to 93% of admissions. Chronic respiratory disease remains the most prominent comorbidity; however, there is also an increase in the percentage of patients with liver disease.Clinical implicationsIn-patient substance misuse units are known to serve individuals with complex illnesses. With service funding cuts, subsequent bed reductions and increased waiting times, this complexity is increasing, with a considerably higher burden of comorbidity. The consequential increased mortality risk highlights the ongoing need for adequate community and in-patient services with integrated care of mental and physical health alongside social work.
DNA damage response pathway alterations and clinical outcome in leiomyosarcoma.
Authors: Rosenbaum Evan , Jonsson Philip , Seier Kenneth , Chi Ping , Dickson Mark Andrew , Gounder Mrinal M. , Kelly Ciara Marie , Keohan Mary Louise , Qin Li-Xuan , Hensley Martee Leigh , D'Angelo Sandra P. , Tap William D. 
Published: February 2020

11048 Background: Leiomyosarcoma (LMS) is a complex karyotype sarcoma with frequent alterations in the homologous recombination (HR) pathway. Genomically unstable tumors with DNA damage repair (DDR) deficiencies may have improved responses to DNA damaging therapies, such as cytotoxic chemotherapy or PARP inhibitors. Methods: We retrospectively reviewed LMS patients treated at MSKCC who had targeted somatic DNA sequencing (MSK-IMPACT) performed on tumor tissue. 33 DDR genes, including 16 HR genes, were analyzed for oncogenic alterations. A composite HR deficiency (HRD) score measured tumor genomic scarring for each patient. To determine if DDR alteration status is prognostic of outcome, we analyzed the recurrence-free survival (RFS) of patients who underwent complete resection, and the overall survival (OS) of the whole cohort. Results: 211 patients had IMPACT testing between March 2014 and October 2018; 48% of samples were primary tumors and 52% recurrent/metastatic sites. Among soft tissue LMS (stLMS), there were 35 men and 55 women. 20% of patients had an oncogenic DDR gene alteration, 72% of which were in the HR pathway (table below). Uterine LMS (uLMS) had more DDR alterations than stLMS, though not statistically significant (p = 0.084). BRCA2 (n = 14 cases), RAD51B (8), and ERCC5 (4) were most frequently altered. HRD score significantly correlated with HRD alteration status (p = 0.004). DDR or HRD altered status and HRD score were associated with shorter RFS in patients with resectable disease, independent of age (p < 0.05). Median OS for the cohort was 75 months (95% CI: 64 – 84). Men with stLMS had shorter OS compared to women (p = 0.025). OS did not significantly differ based on DDR or HRD status (p > 0.05). Conclusions: One-fifth of LMS patients have one or more oncogenic somatic alterations in the DDR pathway, predominantly in effectors of HR. DDR status may be prognostic of recurrence risk. Further analyses to determine the association between DDR status and response to cytotoxic chemotherapy are ongoing. [Table: see text]
Cancer-Related Distress: Revisiting the Utility of the National Comprehensive Cancer Network Distress Thermometer Problem List in Women With Gynecologic Cancers
Authors: Jewett Patricia I. , Teoh Deanna , Petzel Sue , Lee Heewon , Messelt Audrey , Kendall Jeffrey , Hatsukami Dorothy , Everson-Rose Susan A. , Blaes Anne H. , Vogel Rachel I. 
Published: February 2020

PURPOSE: The Distress Thermometer (DT) includes a measure of cancer-related distress and a list of self-reported problems. This study evaluated the utility of the DT problem list in identifying concerns most associated with distress and poorer quality of life (QOL) in survivors of gynecologic cancer. METHODS: Demographic, clinical, psychosocial functioning, and DT data were described among 355 women participating in a gynecologic cancer cohort. Problems from the DT list were ranked by prevalence, distress, and QOL. Logistic regression models explored factors associated with problems that were common (≥ 25% prevalence) and associated with distress and QOL. RESULTS: The average age of participants was 59.9 years (standard deviation [SD], 10.8 years). Most participants were non-Hispanic white (97%) and had ovarian (44%) or uterine (42%) cancer. The mean DT score was 2.7 (SD, 2.7); participants reported a mean of 7.3 problems (SD, 5.9 problems). The most common problems were fatigue (53.6%), worry (49.9%), and tingling (46.3%); least common problems were childcare (2.1%), fevers (2.1%), and substance abuse (1.1%). Report of some common problems, including tingling, sleep, memory, skin issues, and appearance, was not associated with large differences in distress or QOL. In contrast, some rarer problems such as childcare, treatment decisions, eating, housing, nausea, and bathing/dressing were associated with worse distress or QOL. Younger age, lower income, and chemotherapy were risk factors across common problems that were associated with worse distress or QOL (fatigue, nervousness, sadness, fears, and pain). CONCLUSION: The DT problem list did not easily identify concerns most associated with distress and low QOL in patients with gynecologic cancer. Adaptations that enable patients to report their most distressing concerns would enhance clinical utility of this commonly used tool.
Expression of E93 provides an instructive cue to control dynamic enhancer activity and chromatin accessibility during development
Authors: Nystrom Spencer L. , Niederhuber Matthew J. , McKay Daniel J. 
Published: February 2020

ABSTRACT
How temporal cues combine with spatial inputs to control gene expression during development is poorly understood. Here, we test the hypothesis that the Drosophila transcription factor E93 controls temporal gene expression by regulating chromatin accessibility. Precocious expression of E93 early in wing development reveals that it can simultaneously activate and deactivate different target enhancers. Notably, the precocious patterns of enhancer activity resemble the wild-type patterns that occur later in development, suggesting that expression of E93 alters the competence of enhancers to respond to spatial cues. Genomic profiling reveals that precocious E93 expression is sufficient to regulate chromatin accessibility at a subset of its targets. These accessibility changes mimic those that normally occur later in development, indicating that precocious E93 accelerates the wild-type developmental program. Further, we find that target enhancers that do not respond to precocious E93 in early wings become responsive after a developmental transition, suggesting that parallel temporal pathways work alongside E93. These findings support a model wherein E93 expression functions as an instructive cue that defines a broad window of developmental time through control of chromatin accessibility.
Rnf220/Zc4h2-mediated monoubiquitylation of Phox2 is required for noradrenergic neuron development
Authors: Song Ning-Ning , Ma Pengcheng , Zhang Qiong , Zhang Lei , Wang Huishan , Zhang Longlong , Zhu Liang , He Chun-Hui , Mao Bingyu , Ding Yu-Qiang 
Published: February 2020

ABSTRACT
Noradrenaline belongs to the monoamine system and is involved in cognition and emotional behaviors. Phox2a and Phox2b play essential but non-redundant roles during development of the locus coeruleus (LC), the main noradrenergic (NA) neuron center in the mammalian brain. The ubiquitin E3 ligase Rnf220 and its cofactor Zc4h2 participate in ventral neural tube patterning by modulating Shh/Gli signaling, and ZC4H2 mutation is associated with intellectual disability, although the mechanisms for this remain poorly understood. Here, we report that Zc4h2 and Rnf220 are required for the development of central NA neurons in the mouse brain. Both Zc4h2 and Rnf220 are expressed in developing LC-NA neurons. Although properly initiated at E10.5, the expression of genes associated with LC-NA neurons is not maintained at the later embryonic stages in mice with a deficiency of either Rnf220 or Zc4h2. In addition, we show that the Rnf220/Zc4h2 complex monoubiquitylates Phox2a/Phox2b, a process required for the full transcriptional activity of Phox2a/Phox2b. Our work reveals a role for Rnf220/Zc4h2 in regulating LC-NA neuron development, and this finding may be helpful for understanding the pathogenesis of ZC4H2 mutation-associated intellectual disability.
Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation
Authors: Dimchev Georgi , Amiri Behnam , Humphries Ashley C. , Schaks Matthias , Dimchev Vanessa , Stradal Theresia E. B. , Faix Jan , Krause Matthias , Way Michael , Falcke Martin , Rottner Klemens 
Published: February 2020

ABSTRACT
Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin-binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex, an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell-edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.
This article has an associated First Person interview with the first author of the paper.
A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression
Authors: Pirani Vittoria , Métivier Mathieu , Gallaud Emmanuel , Thomas Alexandre , Ku Siou , Chretien Denis , Ettari Roberta , Giet Regis , Corsi Lorenzo , Benaud Christelle 
Published: February 2020

ABSTRACT
A novel 2,3-benzodiazepine-4 derivative, named 1g, has recently been shown to function as an anti-proliferative compound. We now show that it perturbs the formation of a functional mitotic spindle, inducing a spindle assembly checkpoint (SAC)-dependent arrest in human cells. Live analysis of individual microtubules indicates that 1g promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, we found that 1g does not interfere directly with tubulin or perturb microtubule assembly in vitro. The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests that it targets a conserved microtubule regulation module in humans and flies. Altogether, our results indicate that 1g is a novel promising anti-mitotic drug with the unique properties of altering microtubule growth and mitotic spindle organization.
AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture
Authors: Zheng Dongqing , Sussman Jonathan H. , Jeon Matthew P. , Parrish Sydney T. , MacMullan Melanie A. , Delfarah Alireza , Graham Nicholas A. 
Published: February 2020

ABSTRACT
Oncogenes can create metabolic vulnerabilities in cancer cells. We tested how AKT (herein referring to AKT1) and MYC affect the ability of cells to shift between respiration and glycolysis. Using immortalized mammary epithelial cells, we discovered that constitutively active AKT, but not MYC, induced cell death in galactose culture, where cells rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were temporary, and AKT-expressing cells recommenced growth after ∼15 days in galactose. To identify the mechanisms regulating AKT-mediated cell death, we used metabolomics and found that AKT-expressing cells that were dying in galactose culture had upregulated glutathione metabolism. Proteomic profiling revealed that AKT-expressing cells dying in galactose also upregulated nonsense-mediated mRNA decay, a marker of sensitivity to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered that galactose-induced ROS exclusively in cells expressing AKT. Furthermore, ROS were required for galactose-induced death of AKT-expressing cells. We then confirmed that galactose-induced ROS-mediated cell death in breast cancer cells with upregulated AKT signaling. These results demonstrate that AKT but not MYC restricts the flexibility of cancer cells to use oxidative phosphorylation.
This article has an associated First Person interview with the first author of the paper.
Drosophila Prp40 localizes to the histone locus body and regulates gene transcription and development
Authors: Prieto-Sánchez Silvia , Moreno-Castro Cristina , Hernández-Munain Cristina , Suñé Carlos 
Published: February 2020

ABSTRACT
In eukaryotes, a large amount of histones need to be synthesized during the S phase of the cell cycle to package newly synthesized DNA into chromatin. The transcription and 3′ end processing of histone pre-mRNAs are controlled by the histone locus body (HLB), which is assembled on the shared promoter for H3 and H4. Here, we identified the Drosophila Prp40 pre-mRNA processing factor (dPrp40, annotated as CG3542) as a novel HLB component. We showed that dPrp40 is essential for Drosophila development, with functionally conserved activity in vertebrates and invertebrates. We observed that dPrp40 is fundamental in endocycling cells, highlighting a role for this factor in mediating replication efficiency in vivo. The depletion of dPrp40 from fly cells inhibited the transcription, but not the 3′ end processing, of histone mRNA in a H3- and H4-promoter-dependent manner. Our results establish that dPrp40 is an essential protein for Drosophila development that can localize to the HLB and might participate in histone mRNA biosynthesis.
Kinesin KIF18A is a novel PUM-regulated target promoting mitotic progression and survival of a human male germ cell line
Authors: Smialek Maciej Jerzy , Kuczynska Bogna , Ilaslan Erkut , Janecki Damian Mikolaj , Sajek Marcin Piotr , Kusz-Zamelczyk Kamila , Jaruzelska Jadwiga 
Published: February 2020

ABSTRACT
Regulation of proliferation, apoptosis and cell cycle is crucial for the physiology of germ cells. Their malfunction contributes to infertility and germ cell tumours. The kinesin KIF18A is an important regulator of those processes in animal germ cells. Post-transcriptional regulation of KIF18A has not been extensively explored. Owing to the presence of PUM-binding elements (PBEs), KIF18A mRNA is a potential target of PUM proteins, where PUM refers to Pumilio proteins, RNA-binding proteins that act in post-transcriptional gene regulation. We conducted RNA co-immunoprecipitation combined with RT-qPCR, as well as luciferase reporter assays, by applying an appropriate luciferase construct encoding wild-type KIF18A 3′-UTR, upon PUM overexpression or knockdown in TCam-2 cells, representing human male germ cells. We found that KIF18A is repressed by PUM1 and PUM2. To study how this regulation influences KIF18A function, an MTS proliferation assay, and apoptosis and cell cycle analysis using flow cytometry, was performed upon KIF18A mRNA siRNA knockdown. KIF18A significantly influences proliferation, apoptosis and the cell cycle, with its effects being opposite to PUM effects. Repression by PUM proteins might represent one of mechanisms influencing KIF18A level in controlling proliferation, cell cycle and apoptosis in TCam-2 cells.
Propagation properties of the radially polarized Airy vortex beams in a chiral medium
Authors: Yang Qian , Gong Yangyang , Huang Zhancheng , Luo Zhiming , Li Hongyu , Deng Dongmei 
Published: February 2020

We study the propagation of the radially polarized Airy vortex beams (RPAiVBs) in a chiral medium analytically. The RPAiVBs split into the left circular polarization of the RPAiVBs (LCPRPAiVBs) and the right circular polarization of the RPAiVBs (RCPRPAiVBs). We mainly discuss the effects of the vortex and the chiral parameter on the propagation properties of the RPAiVBs, involving the intensity distributions and the radiation forces. It is shown that with the chiral parameter increasing, the intensity focusing position of the RCPRPAiVBs is further from

z

=
0
Zr

, while that of the LCPRPAiVBs is opposite. Besides, the maximum radiation forces of the RCPRPAiVBs are stronger than those of the LCPRPAiVBs. It is significant that we can control the acceleration, the intensity focusing position, and the radiation forces of the RPAiVBs by varying the vortex order and the chiral parameter.
High-power, ultra-broadband supercontinuum light generated in a single-mode fiber pumped with a nanosecond passively Q-switched microchip laser
Authors: Huang Xiaowei , Pan Zhanghao , Hu Aimin , Dong Jun 
Published: February 2020

The compact, high-power, broadband continuum sources are extremely needed for developing portable instruments for various applications such as optical coherence tomography, high-resolution spectroscopy, and so on. Here, we develop a compact high-power, ultra-broadband supercontinuum (SC) light source in a single-mode fiber (SMF) pumped with a

Y
b

:

Y
A
G

/

C
r

4
+

:

Y
A
G

passively

Q

-switched microchip laser oscillating at 1030 nm. The spectral bandwidth of the SC light is over 1150 nm covering from 600 to 1750 nm. The maximum average output power is 181.8 mW at an input pump power of 880 mW. The optical efficiency is 20.6%, and the net conversion efficiency is as high as 51.6% with respect to the pump power coupled into the fiber. The ultra-broadband spectrum of the SC generated in the SMF is caused by the intermodal four-wave mixing (IMFWM) and cascade stimulated Raman scattering effects. Various transverse modes have been experimentally observed in SC beam generated in the SMF. Wavelength-dependent transverse modes propagating in the SMF participating in the IMFWM process dramatically expand the spectral range in the visible region. The experimental results are basically consistent with the theoretical simulations of broadband SC generated in the SMF through the IMFWM process.
Femtosecond pulse delivery around 1560  nm in large-core inhibited-coupling fibers: erratum
Authors: Dobrakowski Dominik , Rampur Anupamaa , Stępniewski Grzegorz , Pysz Dariusz , Zhao Luming , Stepanenko Yuriy , Buczyński Ryszard , Klimczak Mariusz 
Published: February 2020

This erratum reports a correction to the Figs. 8 and 9 of
J. Opt. Soc. Am.
B 36, 3030
(2019)JOBPDE0740-322410.1364/JOSAB.36.003030. Information
regarding the camera used to register a mode profile
is also clarified.
High-repetition-rate 100  W level sodium beacon laser for a multi-conjugate adaptive optics system
Authors: Bian Qi , Bo Yong , Zuo Jun-wei , Feng Lu , Gao Hong-wei , Yuan Lei , Cui Da-fu , Peng Qin-jun , Chen Hong-bin , Xu Zu-yan 
Published: February 2020

A 100 W level kilohertz repetition-rate microsecond (µs)-pulse all-solid-state sodium beacon laser at 589 nm is demonstrated for the first time, to the best of our knowledge, via combining two independent µs-pulsed lasers. Each beamlet is generated by the sum-frequency mixing of pulsed 1064 and 1319 nm lasers in a lithium triborate (LBO) crystal, which operate at 500 Hz pulse repetition frequency with 61 W

p

-polarized and 53 W

s

-polarized output, respectively. An incoherent sequence combining technology of polarized laser beams is employed to add the two beamlets. The average power of the combined beam is up to 107.5 W with a combining efficiency of 94.3%. The combined beam has a 1 kHz repetition rate with

∼

120

µ

s

pulse duration and beam quality

M
2

=

1.41

. The central wavelength with a linewidth of

∼

0.3

G
H
z

is locked to a sodium

D

2
a

absorption line. To the best of our knowledge, this is a record-high power operating at kilohertz for µs-pulsed solid-state sodium beacon lasers.
Broadband amplitude, frequency, and polarization splitter for terahertz frequencies using parallel-plate waveguide technology
Authors: Hernandez-Serrano A. I. , Mittleman Daniel M. , Pickwell-MacPherson Emma 
Published: February 2020

In this Letter, we report a broadband frequency/polarization demultiplexer based on parallel-plate waveguides (PPWGs) for terahertz (THz) frequencies. The fabrication and experimental validation of this polarization sensitive demultiplexer is demonstrated for the range from 0.2 to 1 THz. Upgrading the demultiplexer by adding a second demultiplexer stage, a fifty-fifty amplitude splitter is also demonstrated in the same frequency range. The multiplexer is based on a stainless-steel traveling-wave antenna, exhibiting strong mechanical robustness. This unique device exhibits three splitting mechanisms in the same device: amplitude, polarization, and frequency splitting. This is a significant improvement for the next generation of THz passive components for communication purposes.