bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do care home staff understand, manage and respond to agitation in people with dementia? A qualitative study
Authors: Rapaport Penny , Livingston Gill , Hamilton Olivia , Turner Rebecca , Stringer Aisling , Robertson Sarah , Cooper Claudia 
Published: June 2018

ObjectivesLittle is known about how care home staff understand and respond to distress in residents living with dementia labelled as agitation. The aim of this study was to describe how care home staff understand and respond to agitation and the factors that determine how it is managed.DesignWe conducted a qualitative thematic analysis.SettingWe recruited staff from six care homes in South East England including residential and nursing homes of differing sizes run by both the private and charity sector and located in urban and rural areas.ParticipantsWe interviewed 25 care home staff using purposive sampling to include staff of either sex, differing age, ethnicity, nationality and with different roles and experience.ResultsWe identified four overarching themes: (1) behaviours expressing unmet need; (2) staff emotional responses to agitation; (3) understanding the individual helps and (4) constraints on staff responses. Staff struggled with the paradox of trying to connect with the personhood of residents while seeing the person as separate to and, therefore, not responsible for their behaviours. Staff often felt powerless, frightened and overwhelmed, and their responses were constrained by care home structures, processes and a culture of fear and scrutiny.ConclusionsResponding to agitation expressed by residents was not a linear process and staff faced tensions and dilemmas in deciding how to respond, especially when initial strategies were unsuccessful or when attempts to respond to residents’ needs were inhibited by structural and procedural constraints in the care home. Future trials of psychosocial interventions should support staff to identify and respond to residents’ unmet needs and include how staff can look after themselves.
Intra-articular botulinum toxin A for base-of-thumb osteoarthritis: protocol for a randomised trial (RHIBOT)
Authors: Gil Charlotte , Abdoul Hendy , Campagna Raphaël , Guerini Henri , Ieong Estelle , Chagny Franck , Bedin Catherine , Roren Alexandra , Lefèvre-Colau Marie-Martine , Poiraudeau Serge , Feydy Antoine , Rannou François , Nguyen Christelle 
Published: June 2018

IntroductionRecent studies have suggested that intra-articular injection of botulinum toxin A (BTA) may have analgesic effects in degenerative joint diseases. We aim to assess the efficacy of intra-articular injection of BTA associated with splinting in patients with trapeziometacarpal osteoarthritis (TMC OA).Methods and analysisWe will conduct a randomised double-blind controlled trial. Overall, 60 individuals with TMC OA fulfilling adapted 1990 American College of Rheumatology criteria for hand OA will be recruited in one tertiary care centre in France and randomised to receive splinting + a single ultrasound-guided injection in the TMC joint of 50 Allergan Units of BTA resuspended in 1 mL saline or splinting +1 mL saline. Randomisation will be centralised. The allocation ratio will be 1:1. The primary outcome will be the mean change from baseline in base-of-thumb pain on a self-administered 11-point Numeric Rating Scale in 10-point increments at 3 months after injection. Secondary outcomes will be the mean change in base-of-thumb pain at 1 and 6 months, mean change in hand-specific activity limitations assessed by the self-administered Cochin Hand Function Scale, proportion of responders assessed by the Osteoarthritis Research Society International -Outcome Measures in Rheumatology (OMERACT) criteria and consumption of analgesics and non-steroidal anti-inflammatory drugs assessed by a self-administered 4-class scale at 3 and 6 months. Cointerventions will be allowed in both groups and will be self-reported. Adverse events will be recorded at 3 and 6 months. Participants, care providers and statisticians will be blinded to the allocated treatment.Ethics and disseminationThe RHIBOT trial has been authorised by the Agence Nationale de Sécurité du Médicament and approved by the Comité de Protection des Personnes de Tours Ouest-1. The findings of the study will be disseminated in peer-reviewed journals and at conferences. If the results are positive, intra-articular BTA could be an efficient and safe complementary therapeutic option for patients with TMC OA.Date and version identifier of the protocol8 January 2018, V. 2.0.Trial registration numberNCT03187626; Pre-results.
Correlates of disrupted sleep–wake variables in patients with advanced cancer
Authors: Bernatchez Marie Solange , Savard Josée , Aubin Michèle , Ivers Hans 
Published: June 2018

ObjectivesHigh rates of sleep difficulties have been found in patients with advanced cancer. However, not much is known about factors that are associated with sleep impairments in this population and that could constitute their potential risk factors or consequences. This study conducted in patients with cancer receiving palliative care aimed to evaluate the relationships of subjective (sleep diary; Insomnia Severity Index, ISI) and objective (actigraphy) sleep–wake variables with several physical and psychological symptoms, maladaptive sleep behaviours, erroneous beliefs about sleep, quality of life, time to death and environmental factors.MethodsThe sample was composed of 57 community-dwelling patients with cancer receiving palliative care and with an Eastern Cooperative Oncology Group Scale score of 2 or 3. Actigraphic, light and sound recording and a daily sleep and pain diary were completed for seven consecutive days. A battery of self-report scales was also administered.ResultsGreater disruptions of subjective and objective sleep–wake variables were more consistently associated with worse physical symptoms than with psychological variables. Disrupted objective sleep–wake parameters were also associated with a greater frequency of maladaptive sleep behaviours. Finally, a greater nocturnal noise in the bedroom was correlated with more impairments in subjective and objective sleep–wake variables while a lower 24-hour light exposure was associated with more disruption of subjectively assessed sleep only.ConclusionsAlthough longitudinal studies are needed to establish the etiology of sleep–wake difficulties in patients with advanced cancer, our findings suggest that physical symptoms, maladaptive sleep behaviours and environmental factors can contribute to their development or their persistence and need to be adequately addressed.
A family case with germlineTSC1and mtDNA mutations developing bilateral eosinophilic chromophobe renal cell carcinomas without other typical phenotype of tuberous sclerosis
Authors: Sakamoto Hiromasa , Yamasaki Toshinari , Sumiyoshi Takayuki , Utsunomiya Noriaki , Takeda Masashi , Kamba Tomomi , Nakamura Eijiro , Ogawa Osamu 
Published: June 2018

AimWe examined the genetic alterations in a mother and son with multiple eosinophilic chromophobe renal cell carcinomas (chRCCs) showing no other features.MethodsGermline DNA and bilateral renal cell carcinoma DNA were genetically analysed by whole-exome sequencing. Candidate gene alterations in the first patient’s germline were investigated in her child’s germline and the chRCCs.ResultsWe detected several germline gene alterations in the mother. Among the identified alterations,TSC1and mitochondrial DNA mutations were also confirmed in her son. Regarding somatic alterations in bilateral chRCCs, no common candidate gene alteration was found.ConclusionTo the best of our knowledge, this is the first report of whole-exome sequencing revealing bilateral eosinophilic chRCCs associated with tuberous sclerosis complex in a family case without classical phenotype. These results suggest that germlineTSC1and mitochondrial DNA gene mutations may be involved in the development of chRCCs in some cases.
Examining unmet needs: a cross-sectional study exploring knowledge, attitudes and sexually transmitted infection screening preferences among persons who inject drugs in Camden, New Jersey
Authors: Roth Alexis , Tran Nguyen Khai , Chavis Martha , Van Der Pol Barbara 
Published: June 2018

ObjectivesTo inform the development of targeted sexually transmitted infection (STI) control programmes for persons who inject drugs (PWID).MethodsWe recruited 116 PWID (aged ≥ 18 years) from a community-based syringe exchange programme (SEP) and assessed their STI knowledge and screening preferences via technology assisted self-interview. We estimated prevalence of STI transmission knowledge, attitudes and screening preferences as well as the association between reported sexual behaviours (past 6 months) and willingness to self-collect specimens.ResultsParticipants were white (77%), female (51%) and heterosexual (77%). STI knowledge regarding transmission and testing was high among the sample. More than 70% of participants were aware extragenital infections were possible and were least likely to know urine tests do not detect rectal infections (40.9%). Site-specific specimen collection was highly reflective of reported sexual behaviour. PWID who reported receptive sex (36% vs 5%, p<0.01) and insertive anal sex (31% vs 6%, p=0.01) were more likely to collect rectal specimens than those who did not. A similar trend was seen for oral sex performance on men and self-collection of oropharyngeal swabs (15% vs 3%, p=0.04). In addition, participants preferred collecting their own sample to having a clinician collect it for them (69% vs 31%, p<0.01) and testing at the SEP compared with a STI clinic (86% vs 14%, p<0.01).ConclusionOur findings suggest site-specific specimen collection may be a proxy for risk behaviour engagement in this fairly knowledgeable high-risk population. To increase case finding, STI control programmes should educate patients about site-specific screening and pair outreach with the infrastructure provided by SEPs, in settings where these programmes exist.
Inhibition of Rspo-Lgr4 Facilitates Checkpoint Blockade Therapy by Switching Macrophage Polarization
Authors: Tan Binghe , Shi Xiujuan , Zhang Jie , Qin Juliang , Zhang Na , Ren Hua , Qian Min , Siwko Stefan , Carmon Kendra , Liu Qingyun , Han Honghui , Du Bing , Liu Mingyao 
Published: July 2018

Abstract
Therapies targeting immune checkpoints have shown great clinical potential in a subset of patients with cancer but may be hampered by a failure to reverse the immunosuppressive tumor microenvironment (TME). As the most abundant immune cells in TME, tumor-associated macrophages (TAM) play nonredundant roles in restricting antitumor immunity. The leucine-rich repeat-containing G-protein–coupled receptor 4 (Lgr4, also known as Gpr48) has been associated with multiple physiologic and pathologic functions. Lgr4 and its ligands R-spondin 1–4 have been shown to promote the growth and metastasis of tumor cells. However, whether Lgr4 can promote tumor progression by regulating the function of immune cells in the tumor microenvironment remains largely unknown. Here, we demonstrate that Lgr4 promotes macrophage M2 polarization through Rspo/Lgr4/Erk/Stat3 signaling. Notably, urethane-induced lung carcinogenesis, Lewis lung carcinoma (LLC), and B16F10 melanoma tumors were all markedly reduced in Lgr4fl/flLyz2cre/+ mice, characterized by fewer protumoral M2 TAMs and increased CD8+ T lymphocyte infiltration in the TME. Furthermore, LLC tumor growth was greatly depressed when Rspo/Lgr4/Erk/Stat3 signaling was blocked with either the LGR4 extracellular domain or an anti-Rspo1 antibody. Importantly, blocking Rspo-Lgr4 signaling overcame LLC resistance to anti-PD-1 therapy and improved the efficacy of PD-1 immunotherapy against B16F10 melanoma, indicating vital roles of Rspo-Lgr4 in host antitumor immunity and a potential therapeutic target in cancer immunotherapy.
Significance: This study identifies a novel receptor as a critical switch in TAM polarization whose inhibition sensitizes checkpoint therapy–resistant lung cancer to anti-PD-1 therapy.
Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/17/4929/F1.large.jpg. Cancer Res; 78(17); 4929–42. ©2018 AACR.
High-Throughput Screening of Combinatorial Immunotherapies with Patient-Specific In Silico Models of Metastatic Colorectal Cancer
Authors: Kather Jakob Nikolas , Charoentong Pornpimol , Suarez-Carmona Meggy , Herpel Esther , Klupp Fee , Ulrich Alexis , Schneider Martin , Zoernig Inka , Luedde Tom , Jaeger Dirk , Poleszczuk Jan , Halama Niels 
Published: July 2018

Abstract
Solid tumors are rich ecosystems of numerous different cell types whose interactions lead to immune escape and resistance to immunotherapy in virtually all patients with metastatic cancer. Here, we have developed a 3D model of human solid tumor tissue that includes tumor cells, fibroblasts, and myeloid and lymphoid immune cells and can represent over a million cells over clinically relevant timeframes. This model accurately reproduced key features of the tissue architecture of human colorectal cancer and could be informed by individual patient data, yielding in silico tumor explants. Stratification of growth kinetics of these explants corresponded to significantly different overall survival in a cohort of patients with metastatic colorectal cancer. We used the model to simulate the effect of chemotherapy, immunotherapies, and cell migration inhibitors alone and in combination. We classified tumors according to tumor and host characteristics, showing that optimal treatment strategies markedly differed between these classes. This platform can complement other patient-specific ex vivo models and can be used for high-throughput screening of combinatorial immunotherapies.
Significance: This patient-informed in silico tumor growth model allows testing of different cancer treatment strategies and immunotherapies on a cell/tissue level in a clinically relevant scenario. Cancer Res; 78(17); 5155–63. ©2018 AACR.
CD8+ T-Cell Density Imaging with 64Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols
Authors: Seo Jai Woong , Tavaré Richard , Mahakian Lisa M. , Silvestrini Matthew T. , Tam Sarah , Ingham Elizabeth S. , Salazar Felix B. , Borowsky Alexander D. , Wu Anna M. , Ferrara Katherine W. 
Published: July 2018

Abstract
Purpose: Noninvasive and quantitative tracking of CD8+ T cells by PET has emerged as a potential technique to gauge response to immunotherapy. We apply an anti-CD8 cys-diabody, labeled with 64Cu, to assess the sensitivity of PET imaging of normal and diseased tissue.
Experimental Design: Radiolabeling of an anti-CD8 cys-diabody (169cDb) with 64Cu was developed. The accumulation of 64Cu-169cDb was evaluated with PET/CT imaging (0, 5, and 24 hours) and biodistribution (24 hours) in wild-type mouse strains (n = 8/group studied with imaging and IHC or flow cytometry) after intravenous administration. Tumor-infiltrating CD8+ T cells in tumor-bearing mice treated with CpG and αPD-1 were quantified and mapped (n = 6–8/group studied with imaging and IHC or flow cytometry).
Results: We demonstrate the ability of immunoPET to detect small differences in CD8+ T-cell distribution between mouse strains and across lymphoid tissues, including the intestinal tract of normal mice. In FVB mice bearing a syngeneic HER2-driven model of mammary adenocarcinoma (NDL), 64Cu-169cDb PET imaging accurately visualized and quantified changes in tumor-infiltrating CD8+ T cells in response to immunotherapy. A reduction in the circulation time of the imaging probe followed the development of treatment-related liver and splenic hypertrophy and provided an indication of off-target effects associated with immunotherapy protocols.
Conclusions: 64Cu-169cDb imaging can spatially map the distribution of CD8+ T cells in normal organs and tumors. ImmunoPET imaging of tumor-infiltrating cytotoxic CD8+ T cells detected changes in T-cell density resulting from adjuvant and checkpoint immunotherapy protocols in our preclinical evaluation. Clin Cancer Res; 24(20); 4976–87. ©2018 AACR.
The Anticancer Activity of a First-in-class Small-molecule Targeting PCNA
Authors: Gu Long , Lingeman Robert , Yakushijin Fumiko , Sun Emily , Cui Qi , Chao Jianfei , Hu Weidong , Li Hongzhi , Hickey Robert J. , Stark Jeremy M. , Yuan Yate-Ching , Chen Yuan , Vonderfecht Steven L. , Synold Timothy W. , Shi Yanhong , Reckamp Karen L. , Horne David , Malkas Linda H. 
Published: July 2018

Abstract

Purpose:
Proliferating cell nuclear antigen (PCNA) plays an essential role in regulating DNA synthesis and repair and is indispensable to cancer cell growth and survival. We previously reported a novel cancer associated PCNA isoform (dubbed caPCNA), which was ubiquitously expressed in a broad range of cancer cells and tumor tissues, but not significantly in nonmalignant cells. We found the L126-Y133 region of caPCNA is structurally altered and more accessible to protein–protein interaction. A cell-permeable peptide harboring the L126-Y133 sequence blocked PCNA interaction in cancer cells and selectively kills cancer cells and xenograft tumors. On the basis of these findings, we sought small molecules targeting this peptide region as potential broad-spectrum anticancer agents.

Experimental Design:
By computer modeling and medicinal chemistry targeting a surface pocket partly delineated by the L126-Y133 region of PCNA, we identified a potent PCNA inhibitor (AOH1160) and characterized its therapeutic properties and potential toxicity.

Results:
AOH1160 selectively kills many types of cancer cells at below micromolar concentrations without causing significant toxicity to a broad range of nonmalignant cells. Mechanistically, AOH1160 interferes with DNA replication, blocks homologous recombination–mediated DNA repair, and causes cell-cycle arrest. It induces apoptosis in cancer cells and sensitizes them to cisplatin treatment. AOH1160 is orally available to animals and suppresses tumor growth in a dosage form compatible to clinical applications. Importantly, it does not cause significant toxicity at 2.5 times of an effective dose.

Conclusions:
These results demonstrated the favorable therapeutic properties and the potential of AOH1160 as a broad-spectrum therapeutic agent for cancer treatment.
Trzcianne – studium przypadku. Wojna polsko-polska o Żydów w relacjach świadków [Trzcianne – a case study. The Polish-Polish war over Jews in witness accounts]
Authors: Konopa Łukasz 
Published: July 2018

Trzcianne – a case study. The Polish-Polish war over Jews in witness accountsŁukasz Konopa endeavors to reconstruct the process of the annihilation of Trzcianne, a town where the Jewish population was dominant before 1939. This case study is based on ethnographic interviews conducted presently with members of the Wasilewski family, the Righteous among the Nations, who both witnessed and participated in the events. The paper also refers to the accounts presented after the war by the surviving Jews and witness testimonies given during the trial conducted in 1950–51 against a few Poles accused of murdering Jews. In the course of his analysis, the author reveals the silence and secrecy surrounding the fact that some Poles were involved in the murder of Jews whereas those who risked their lives to help Jews were punished by their Polish neighbors after the war. The shameful episodes in the past of a small town in the Podlasie region were deleted from the local historical discourse. Trzcianne – studium przypadku. Wojna polsko-polska o Żydów w relacjach świadkówAutor podejmuje próbę rekonstrukcji obrazu zagłady Trzciannego, miejscowości, której ogromną większość populacji przed 1939 rokiem stanowili Żydzi. Studium przypadku oparte jest na wywiadach etnograficznych, przeprowadzonych współcześnie z członkami rodziny państwa Wasilewskich – świadkami oraz uczestnikami wydarzeń, Sprawiedliwymi wśród Narodów Świata. Przywołane zostają również relacje złożone po wojnie przez ocalałych Żydów oraz zeznania świadków z procesu sądowego kilku Polaków oskarżonych o mordowanie Żydów, prowadzonego w latach 1950–1951. W toku analiz autor odsłania przemilczaną i ukrywaną społecznie prawdę, iż niektórzy Polacy brali udział w mordowaniu osób wyznania mojżeszowego. Natomiast ci, którzy z narażeniem życia pomagali Żydom, ponieśli po wojnie karę ze strony swoich polskich sąsiadów. Wstydliwe epizody z przeszłości małego, podlaskiego miasteczka zostały wyparte z lokalnego dyskursu historycznego.
Odpowiedź Krzysztofowi Persakowi [Reply to Krzysztof Persak]
Authors: Tryczyk Mirosław 
Published: July 2018

Reply to Krzysztof PersakThis is a reply to the review of author’s book Miasta śmierci. Sąsiedzkie pogromy Żydów [Cities of death. Jewish pogroms by neighbors] penned by Dr Krzysztof Persak in Zagłada Żydów (2016).Odpowiedź Krzysztofowi PersakowiOdpowiedź na recenzję książki autora, Miasta śmierci. Sąsiedzkie pogromy Żydów, pióra dra Krzysztofa Persaka, zamieszczoną w czasopiśmie „Zagłada Żydów” (2016).
Tough Love: A Diasporic Critique of the Palestinian Boycott, Divestment, and Sanctions Movement
Authors: Ghabra Haneen S. , Hasian Marouf A. 
Published: June 2018

The authors use a diasporic critique of Palestinian Boycott, Divestment, and Sanctions (BDS) movements to argue that some of these movements undermine chances for two-state solutions. The authors, provide a nuanced way of evaluating both the theoretical and pragmatic dimensions of BDS. The argument is advanced that those in the diaspora have a nomadic positionality that allows them to uniquely critique venues such as (BDS), The Electronic Intifada, and Mondoweiss as they analyze the rhetoric of Palestinian nationalist movements. Diasporic critiques are able to trace the fissures, the ossifications, and the ruptures that take place in the Middle East as various acts of territoriality, deterritoriality, and reterritorialization take place simultaneously.
Association between epicardial adipose tissue, high-sensitivity C-reactive protein and myocardial dysfunction in middle-aged men with suspected metabolic syndrome
Authors: Cho Dong-Hyuk , Joo Hyung Joon , Kim Mi-Na , Lim Do-Sun , Shim Wan Joo , Park Seong-Mi 
Published: June 2018

Abstract
Background
As body fat composition and metabolism differ between men and women, we evaluated sex-related differences in the association among epicardial adipose tissue (EAT), secretome profile, and myocardial function of subjects with suspected metabolic syndrome.

Methods
We evaluated 277 participants (men, n = 140; 56.1 ± 4.7 years) who underwent conventional echocardiography and two-dimensional speckle tracking from the Seoul Metabolic Syndrome cohort. EAT was measured from the right ventricular free wall perpendicular to the aortic annulus at end systole. Global longitudinal strain (GLS) was obtained from 18 apical segments. Apolipoprotein A1, apolipoprotein B, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) levels were measured using immunoturbidimetry assay.

Results
Mean age, body mass index, and hs-CRP level did not differ by sex. Waist circumference, fasting blood glucose level, and triglyceride/high-density lipoprotein cholesterol ratio were higher, and apolipoprotein AI and adiponectin levels were lower in men. No significant difference in mean EAT thickness was found (7.02 ± 1.81 vs. 7.13 ± 1.70 mm, p = 0.613). Men had a higher left ventricular (LV) mass index and lower GLS. EAT thickness was associated with hs-CRP level in men alone (ß = 0.206, p = 0.015). LV mass index (ß = 2.311, p = 0.037) and function represented by e′ (ß = − 0.279, p = 0.001) and GLS (ß = − 0.332, p < 0.001) were independently associated with EAT thickness in men alone.

Conclusions
In middle-aged subjects with suspected metabolic syndrome, EAT was associated with inflammation represented by hs-CRP level, LV mass, and subclinical myocardial dysfunction only in men, suggesting that the inflammatory activity of EAT induced myocardial remodeling and dysfunction in middle-aged subjects but was attenuated in women.
Trial registration NCT02077530 (date of registration: November 1, 2013)