bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children
Authors: Korpela Katri , Salonen Anne , Virta Lauri J. , Kekkonen Riina A. , Forslund Kristoffer , Bork Peer , de Vos Willem M. 
Published: January 2016

AbstractEarly-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2–7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.
Modelling the Tox21 10 K chemical profiles for in vivo toxicity prediction and mechanism characterization
Authors: Huang Ruili , Xia Menghang , Sakamuru Srilatha , Zhao Jinghua , Shahane Sampada A. , Attene-Ramos Matias , Zhao Tongan , Austin Christopher P. , Simeonov Anton 
Published: January 2016

AbstractTarget-specific, mechanism-oriented in vitro assays post a promising alternative to traditional animal toxicology studies. Here we report the first comprehensive analysis of the Tox21 effort, a large-scale in vitro toxicity screening of chemicals. We test ∼10,000 chemicals in triplicates at 15 concentrations against a panel of nuclear receptor and stress response pathway assays, producing more than 50 million data points. Compound clustering by structure similarity and activity profile similarity across the assays reveals structure–activity relationships that are useful for the generation of mechanistic hypotheses. We apply structural information and activity data to build predictive models for 72 in vivo toxicity end points using a cluster-based approach. Models based on in vitro assay data perform better in predicting human toxicity end points than animal toxicity, while a combination of structural and activity data results in better models than using structure or activity data alone. Our results suggest that in vitro activity profiles can be applied as signatures of compound mechanism of toxicity and used in prioritization for more in-depth toxicological testing.
Applications of time-series analysis to mood fluctuations in bipolar disorder to promote treatment innovation: a case series
Authors: Holmes E A , Bonsall M B , Hales S A , Mitchell H , Renner F , Blackwell S E , Watson P , Goodwin G M , Di Simplicio M 
Published: January 2016

AbstractTreatment innovation for bipolar disorder has been hampered by a lack of techniques to capture a hallmark symptom: ongoing mood instability. Mood swings persist during remission from acute mood episodes and impair daily functioning. The last significant treatment advance remains Lithium (in the 1970s), which aids only the minority of patients. There is no accepted way to establish proof of concept for a new mood-stabilizing treatment. We suggest that combining insights from mood measurement with applied mathematics may provide a step change: repeated daily mood measurement (depression) over a short time frame (1 month) can create individual bipolar mood instability profiles. A time-series approach allows comparison of mood instability pre- and post-treatment. We test a new imagery-focused cognitive therapy treatment approach (MAPP; Mood Action Psychology Programme) targeting a driver of mood instability, and apply these measurement methods in a non-concurrent multiple baseline design case series of 14 patients with bipolar disorder. Weekly mood monitoring and treatment target data improved for the whole sample combined. Time-series analyses of daily mood data, sampled remotely (mobile phone/Internet) for 28 days pre- and post-treatment, demonstrated improvements in individuals’ mood stability for 11 of 14 patients. Thus the findings offer preliminary support for a new imagery-focused treatment approach. They also indicate a step in treatment innovation without the requirement for trials in illness episodes or relapse prevention. Importantly, daily measurement offers a description of mood instability at the individual patient level in a clinically meaningful time frame. This costly, chronic and disabling mental illness demands innovation in both treatment approaches (whether pharmacological or psychological) and measurement tool: this work indicates that daily measurements can be used to detect improvement in individual mood stability for treatment innovation (MAPP).
In‐vitro study of human proximal femur microstructure: analysis of the relationship between micro‐computed tomography data and quantitative ultrasound parameters
Authors: Peccarisi Marco , De Marco Tommaso , Conversano Francesco , Pisani Paola , Spedicato Luigi , Greco Antonio , Panetta Daniele , Guido Giulio , Bottai Vanna , Salvadori Piero A. , Casciaro Sergio 
Published: January 2016

The aim of this study was to investigate the relationships between selected quantitative ultrasound (QUS) parameters and human femur microstructure properties, as quantified by micro‐computed tomography (micro‐CT). The authors employed an innovative custom‐designed experimental set‐up, which allowed the insonification of each portion of an excised femoral head sample, simultaneously including trabecular region, cortical layer and cartilage in their physiologic morphological configuration. Thirty different, uniformly distributed, regions of interest were analysed for the calculation of apparent integrated backscatter (AIB), integrated reflection coefficient (IRC) and several micro‐CT parameters. QUS data acquisitions were performed through both single‐element ultrasound transducers at two different frequencies (2.25 and 3.5 MHz) and a clinically available 128‐element echographic probe. Obtained results showed that AIB was strongly correlated with trabecular network properties (|r| up to 0.80) and IRC had appreciable linear correlations with cortical bone density (|r| up to 0.57). The agreement between single‐element transducers and echographic probe, combined with the innovative approach of considering the entire femoral head in its physiological shape with all its components (cartilage, cortical layer, trabecular region), encourages the clinical translation of the proposed approach as a possible new method for early osteoporosis diagnosis.
Transketolase counteracts oxidative stress to drive cancer development
Authors: Xu Iris Ming-Jing , Lai Robin Kit-Ho , Lin Shu-Hai , Tse Aki Pui-Wah , Chiu David Kung-Chun , Koh Hui-Yu , Law Cheuk-Ting , Wong Chun-Ming , Cai Zongwei , Wong Carmen Chak-Lui , Ng Irene Oi-Lin 
Published: January 2016

Significance
Excessive accumulation of oxidative stress is harmful to cancer cells. Our study demonstrates the important roles of a pentose phosphate pathway (PPP) enzyme, transketolase (TKT), in redox homeostasis in cancer development. We highlight the clinical relevance of TKT expression in cancers. We also show that TKT overexpression in cancer cells is a response of Nuclear Factor, Erythroid 2-Like 2 (NRF2) activation, a sensor to cellular oxidative stress. TKT locates at an important position that connects PPP with glycolysis to affect production of antioxidant NADPH. Our preclinical study shows that targeting TKT leads to elevation of oxidative stress, making cancer cells more vulnerable to therapeutic treatment, such as Sorafenib. Using TKT as an example, our study suggests that targeting enzymes for antioxidant production represents a direction for cancer treatment.
Observation of femtosecond X-ray interactions with matter using an X-ray–X-ray pump–probe scheme
Authors: Inoue Ichiro , Inubushi Yuichi , Sato Takahiro , Tono Kensuke , Katayama Tetsuo , Kameshima Takashi , Ogawa Kanade , Togashi Tadashi , Owada Shigeki , Amemiya Yoshiyuki , Tanaka Takashi , Hara Toru , Yabashi Makina 
Published: January 2016

Significance
Understanding ultraintense light–matter interactions is an intriguing subject from viewpoints of basic science and practical applications. For the X-ray region, such research fields have opened up with the emergence of X-ray free-electron lasers (XFELs). By using an X-ray–X-ray pump–probe scheme, we firstly measured atomic response to XFEL light with femtosecond–ångstrom time–space resolutions. It was found that the atomic position is freezing until 20 fs after the XFEL irradiation, which supports the feasibility of damageless structural determinations with ultraintense XFEL pulses. The pump–probe scheme demonstrated here is an effective way to capture X-ray–matter interactions, and would contribute to verify and improve theory of X-ray interactions with matter, and stimulate advanced XFEL applications.
Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa
Authors: Oh Ji Eun , Kim Byoung-Chan , Chang Dong-Ho , Kwon Meehyang , Lee Sun Young , Kang Dukjin , Kim Jin Young , Hwang Inhwa , Yu Je-Wook , Nakae Susumu , Lee Heung Kyu 
Published: January 2016

Significance
Protective mechanisms of commensal bacteria against viral infection are limited to how immune inductive signals are provided by commensal bacteria for enhancing immunity. Whether, or how, commensal bacteria might influence the effector arm of immune responses remains unknown. Here, we demonstrate that dysbiosis within the vaginal microbiota results in severe impairment of antiviral protection against herpes simplex virus type 2 infection. IL-33 released into the vaginal tract after antibiotic treatment blocks the ability of effector T cells to migrate into the vaginal tissue and secrete the antiviral cytokine, IFN-γ. Thus, our findings suggest a previously unstudied role of commensal bacteria in the effector phase of the antiviral immune response against genital herpes.
Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling
Authors: Jahan Akhee S. , Lestra Maxime , Swee Lee Kim , Fan Ying , Lamers Mart M. , Tafesse Fikadu G. , Theile Christopher S. , Spooner Eric , Bruzzone Roberto , Ploegh Hidde L. , Sanyal Sumana 
Published: January 2016

Significance
We used an unbiased screening strategy to capture deubiquitylases that participate in T cell receptor signaling in primary cells under physiological settings. We identified ubiquitin-specific peptidase (Usp) 12 as a crucial component of TCR expression at the cell surface, and found supporting evidence for its function by creating an inducible genetic knockout in Jurkat cells. Using proximity-based labeling, we identified LAT and Trat1 as substrates of Usp12. In Usp12-deficient cells, both LAT and Trat1 are ubiquitin-modified and lysosomally degraded, thus down-regulating TCR surface expression. Our data define a role of Usp12 in the TCR signaling pathway for the first time, to our knowledge. These results underscore the importance of deubiquitylases in fine-tuning signaling cascades and provide a basis for the screening of small molecules to identify potential inhibitors.
A practice framework to support the Care Act 2014
Authors: Stanley Tony 
Published: January 2016

Purpose
– The purpose of this paper is to discuss how the signs of safety and wellbeing practice framework offers a practical and logical reinforcement for the Making Safeguarding Personal programme within the practice context of the Care Act. The new practice framework orientates safeguarding practice to be person led and person centred while reinforcing an outcomes focus.

Design/methodology/approach
– The principal social worker co-led the design and pilot programme where the new practice framework was developed and trialled.

Findings
– A practice framework that houses the policy and practice updates needed to deliver the Care Act and Making Safeguarding Personal agenda is logical and necessary for the practitioners. An outcomes focus is encouraged because safeguarding practice is goal orientated and outcome focused.

Practical implications
– A debate about how practice frameworks can help achieve the Making Safeguarding Personal approach and deliver on the Care Act principles is offered. This is a new and important debate for adult social care; a debate well-established across children’s services.

Originality/value
– A debate about how practice frameworks can help achieve the Making Safeguarding Personal approach and deliver on the Care Act principles is offered. This is a new and important debate for adult social care; a debate well-established across children’s services.
Perspectives of rural carers on benefits and barriers of receiving occupational therapy via Information and Communication Technologies
Authors: Gardner Kate , Bundy Anita , Dew Angela 
Published: January 2016

IntroductionPeople with a disability living in rural areas commonly experience difficulty in accessing therapy services. Information and Communication Technologies (ICT) may have the potential to provide occupational therapy services remotely through two‐way visual interactions. The aim of this qualitative study was to understand the perspectives of carers of a person with a disability living in rural New South Wales (NSW) on the use of ICT for occupational therapy service delivery.MethodsIndividual semi‐structured telephone interviews were conducted with 11 carers of persons with a disability living in rural NSW. Participants were asked about their use of technology, therapy experiences and their attitudes towards using ICT to receive occupational therapy for their son/daughter. Data were analysed via constant comparison and thematic analysis.ResultsParticipants were willing to use ICT to enhance their current access to therapy based on their in‐depth knowledge of their son or daughter and their prior experiences with therapy and technology. For ICT to work for occupational therapy, participants identified the need for support and access prior to, during and between ICT sessions.ConclusionFrom the carers’ perspectives, ICT has the potential to increase access to occupational therapy services for people with a disability who live in rural NSW. Occupational therapists could benefit from eliciting the experiences, knowledge and willingness of rural carers to deliver therapy via ICT, thereby supplementing and enhancing in‐person service delivery.
Seeking mental health information and support online: experiences and perspectives of young people receiving treatment for first‐episode psychosis
Authors: Lal Shalini , Nguyen Valentin , Theriault Joanie 
Published: January 2016

AbstractAimLimited knowledge exists on youth mental health service users' experiences and perspectives of seeking mental health information, services and support online. Such information is important for developing online resources that are tailored to the needs of youth with different types of mental health concerns. The purpose of this study was to better understand the experiences and perspectives of young people receiving treatment for first‐episode psychosis (FEP) on using web‐based and mobile technologies for accessing mental health information, services and support.MethodsA qualitative approach using focus group methods was used. Seventeen participants between the ages of 21 and 35 were recruited from a specialized early intervention program for psychosis. A thematic analysis was conducted.ResultsThe results are organized under three related themes: striving towards a better understanding of the illness and treatment; encountering multiple issues with accessing information online; and valuing online mental health information and support. The majority of participants described online activities related to information and support, rather than specific types of mental health services or interventions.ConclusionsYouth receiving treatment for FEP value accessing mental health information and support online; however, they encounter several challenges in this regard. The findings can inform the development of online resources and strategies that meet the needs of service users. This study also highlights the importance for mental healthcare professionals to address the topic of online mental health information and support seeking within the context of providing services to young people.
Constraints on the biological recovery of the Bohemian Forest lakes from acid stress
Authors: Vrba Jaroslav , Bojková Jindřiška , Chvojka Pavel , Fott Jan , Kopáček Jiří , Macek Miroslav , Nedbalová Linda , Papáček Miroslav , Rádková Vanda , Sacherová Veronika , Soldán Tomáš , Šorf Michal 
Published: January 2016

Summary

The response of planktonic (phytoplankton, ciliates, rotifers and crustaceans) and littoral (Ephemeroptera, Plecoptera, Trichoptera and Heteroptera: Nepomorpha) assemblages to chemical recovery was studied over a twelve‐year period (1999–2011) in eight glacial lakes in the Bohemian Forest (central Europe). The region suffered from high atmospheric pollution from the 1950s to the late 1980s, but has since been recovering from acidification due to 86% and 44% decrease in sulphur and nitrogen deposition, respectively, during the 1990s–2000s. Despite the rapid improvement in water chemistry of all the eight studied lakes, only four have partly recovered so far (low‐aluminium lakes), while the other four lakes still remain strongly acidic (high‐aluminium lakes).

All present lake assemblages are dissimilar by 40–90% from those during the early phase of chemical recovery as a result of species (re)colonisation (ciliates, crustaceans and insects) in the high‐Al lakes, and considerable species replacement (zooplankton) and (re)colonisation (insects) in the low‐Al lakes. Phytoplankton remained very similar in the high‐Al lakes, but changed (loss and/or replacement of some acid‐tolerant species) in the low‐Al lakes.

Aluminium (Al) concentrations were dominant in structuring the assemblages of phytoplankton, rotifers and Nepomorpha, but also affected crustaceans through the seston carbon to phosphorus (P) ratio. Both direct (toxicity) and indirect (P availability) effects of Al control biological recovery in the Bohemian Forest lakes. A concentration of 200 μg L−1 of total Al is the main barrier preventing the high‐Al lakes from recovery. In contrast, pH and total P rather than Al significantly influenced Ephemeroptera, Plecoptera and Trichoptera.

Although biotic responses (especially in the low‐Al lakes) showed important signs of recovery, such as reappearance of some indigenous or acid‐sensitive species, decline in eurytopic acid‐tolerant species and colonisation by vagile species, the assemblages of all the lakes still suffer from acid stress. Our results also indicate an increasing role of biotic interactions between colonisers and residents leading to the reconstruction of aquatic food webs in the low‐Al lakes.
Healthcare needs of displaced women: Osire refugee camp, Namibia
Authors: Pinehas Lusia N. , van Wyk Neltjie C. , Leech Ronell 
Published: January 2016

AimThe aim of this study was to explore and describe the experiences of healthcare needs of displaced women in the Osire refugee camp in Namibia.BackgroundNamibia is a country where displaced people from other African countries seek refuge as a result of their own country's political instability. All displaced people are hosted in the Osire camp, which is a highly protected area. There are more women than men in the camp and their health is often compromised.MethodsIn this descriptive phenomenological study, the natural dimension of the experiences of the participants of their healthcare needs were explored through in‐depth interviews and reflected upon through transcendental processes to formulate the phenomenological dimension thereof.FindingsThe essence of displaced women′s healthcare needs was “the need for the restoration of hope and human dignity”. Their needs refer to measures to enhance their autonomy and freedom; skills training; certainty about their future; security with aid distribution; protection against stigmatization due to human immunodeficiency virus (HIV) infection; protection against abuse; and participation in reproductive health care.DiscussionWhen displaced women are admitted in a camp they lose their freedom to make decisions about everyday functioning and future. They thus develop feelings of insecurity and vulnerability.ConclusionThe participants referred to several factors that were detrimental for their well‐being. The essence of their needs was “the need for the restoration of hope and human dignity” that could only be achieved when their needs are addressed.Implications for nursingAs nurses are in close contact with displaced women in refugee camps they should negotiate opportunities for the women to discuss their concerns with the camp officials.Implications for health and social development policyPolicies should make provision for the involvement of displaced people in all aspects that relate to their everyday and future living arrangements.
Lewy‐ and Alzheimer‐type pathologies in midbrain and cerebellum across the Lewy body disorders spectrum
Authors: Sierra M. , Gelpi E. , Martí M. J. , Compta Y. 
Published: January 2016

AimsParkinson's disease (PD) and dementia with Lewy bodies (DLB) are pathologically characterized by intraneuronal α‐synuclein aggregates and thus labelled as Lewy body disorders (LBD). Conjoint cortical α‐synuclein, tau and amyloid‐β (Aβ), and striatal Aβ aggregates, have been related to dementia in LBD. Interpretation of current and emerging in vivo molecular imaging of these pathologies will need of precise knowledge of their topographic distribution. We aimed to assess these pathologies further down the encephalon across the LBD‐spectrum.MethodsSemiquantitative rating of α‐synuclein, Aβ and hyperphosphorylated tau aggregates in midbrain (and cerebellum in the case of Aβ as it represents the last β‐amyloidosis stage) sections from cases representative of the LBD‐spectrum (PD non‐dementia, PD‐dementia, DLB; n = 10 each) compared to controls (n = 10) and Alzheimer's disease (AD; n = 10).Resultsα‐synuclein midbrain scores rose from controls to AD and then LBD irrespective of dementia. Aβ and tau were more prominent in the tectum/tegmentum, increasing from controls to LBD (mostly in dementia cases in the case of Aβ), and then peaking in AD. By contrast, cerebellar Aβ scores were marginal across the LBD‐spectrum, as opposed to AD, only showing a trend towards greater involvement in LBD cases with dementia.ConclusionsFrequency and severity of Aβ and tau pathologies in the midbrain across the LBD‐spectrum were midway between controls and AD, with Aβ in the tectum/tegmentum being associated with dementia. These findings might have potential implications in the eventual interpretation of regional uptake of in vivo molecular imaging of these pathologies.