bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting the progressive resistance and balance training response of community‐dwelling older adults accessing aged care support services: A stepped‐wedge randomised controlled trial
Authors: Keogh Justin W. L. , Henwood Tim , Hetherington Sharon , Gardiner Paul A. , Tuckett Anthony G. , Rouse Kevin , Swinton Paul 
Published: February 2022

AbstractObjectiveTo quantify the variation in body composition, physical function and cognitive health changes resulting from the Muscling Up Against Disability (MUAD) resistance and balance training program and the potential for baseline characteristics to predict the magnitude of training‐related response.MethodsThe study represented a secondary analysis of a stepped‐wedge randomised controlled trial involving 245 community‐dwelling adults receiving Australian Government–funded aged care services who performed 26 weeks of supervised progressive resistance and balance training (PRBT). The primary outcome was the proportion of response that described the number of individuals expected to make any positive change due to the intervention and not external factors.ResultsFor all outcomes, the observed average change in the PRBT group was more favourable than the control. Analyses identified that most participants completing the PRBT program would be expected to respond positively to the intervention (86%–99%) with respect to their physical performance (SPPB summary, grip strength, chair stand and isometric knee strength). A smaller proportion completing the PRBT program group would be expected to respond positively in aspects of body composition (45%–60%) or cognitive function (44%–84%). The strongest predictors of positive change were baseline physical function, whereby those with the poorest baseline function experienced the greatest benefits.ConclusionsThis study strongly supports the promotion of PRBT as a standard component of any care plan for community‐dwelling older adults, especially those with low levels of physical function.
Warfarin‐induced skin necrosis after the use of an anticoagulation reversal agent
Authors: Zhang Lois , Truong Kelvin , Chan Linda , Kim Jennifer , Fernandez‐Peñas Pablo 
Published: February 2022

ABSTRACTAnticoagulant‐induced skin necrosis is a rare and potentially life‐threatening complication of anticoagulant therapy. The majority of cases of anticoagulant‐induced skin necrosis have been attributed to warfarin, known as warfarin‐induced skin necrosis (WISN). The use of anticoagulation reversal agents such as Prothrombinex‐VF in the development of WISN is not a commonly documented phenomenon. The authors present a case of WISN post‐recommencement of warfarin and the use of Prothrombinex‐VF.
Regulatory focus theory: Disentangling goals and strategies
Authors: Vriend Tim , Hamstra Melvyn R. W. , Said Ramzi , Janssen Onne , Jordan Jennifer , Nijstad Bernard A. 
Published: February 2022

AbstractThe purpose of this research was to develop and test the Regulatory Goals and Strategies Questionnaire (RGSQ) to promote conceptual and empirical clarity in the literature on regulatory focus theory (RFT). According to RFT, construing an end‐state as a maximal goal (ideal, gain, and advancement) elicits the adoption of an eager promotion‐focused strategy, whereas construing an end‐state as a minimal goal (ought, non‐loss, and security) elicits the adoption of a vigilant prevention‐focused strategy. This means that promotion‐focused eagerness and prevention‐focused vigilance can be elicited by various goals and that eager and vigilant strategies are in fact separate from goals. However, extant measurement instruments have not treated them as such. The RGSQ was developed to distinguish various maximal and minimal goals and to separate these goals from promotion‐ and prevention‐focused strategies of eagerness and vigilance. Across three studies that combine six samples (total N = 1848), we examined the factor structure and nomological network of the RGSQ (Study 1: four samples of students and adults) and its predictive validity in a task context (Study 2) and working sample (Study 3). Overall, we found support for the RGSQ's validity and demonstrated that the RGSQ operationalizes regulatory focus in accordance with the theory's core assumptions.
Review article: randomised controlled trials in inflammatory bowel disease—common challenges and potential solutions
Authors: Schreiber Stefan , Irving Peter M. , Sharara Ala I. , Martín‐Arranz María Dolores , Hébuterne Xavier , Penchev Plamen , Danese Silvio , Anthopoulos Prodromos , Akhundova‐Unadkat Gamar , Baert Filip 
Published: February 2022

SummaryBackgroundRecruitment rates for Crohn’s disease and ulcerative colitis clinical trials continue to decrease annually. The inability to reach recruitment targets and complete trials has serious implications for stakeholders in the inflammatory bowel disease (IBD) community. Action is required to ensure patients with an unmet medical need have access to new therapies to improve the management of their IBD.AimsIdentify challenges contributing to recruitment decline in IBD clinical trials and propose potential solutions.MethodsPubMed and Google were used to identify literature, regulatory guidelines and conference proceedings related to IBD clinical trials and related concepts. Data on IBD clinical trials conducted between 1989 and 2020 were extracted from the Trialtrove database.ResultsKey aspects that may improve recruitment rates were identified. An increasingly patient‐centric approach should be taken to study design including improvements to the readability of key trial documentation and inclusion of patient representatives in trial planning. Placebo is unappealing to patients; approaches including platform trials should be explored to minimise placebo exposure. Non‐invasive imaging, biomarkers and novel digital endpoints should continue to be examined to reduce the burden on patients. Reducing the administrative burden associated with trials via the use of electronic signatures, for example, may benefit study sites and investigators. Changes implemented to IBD trials during the COVID‐19 pandemic provided examples of how trial conduct can be rapidly and constructively adapted.ConclusionsTo improve recruitment in Crohn’s disease and ulcerative colitis trials, the IBD community should address a broad range of issues related to clinical trial conduct.
The association of four genetic variants with myelosuppression in gemcitabine‐treated Japanese is not evident in gemcitabine/carboplatin‐treated Swedes
Authors: Björn Niclas , Jakobsen Ingrid , Udagawa Chihiro , Brandén Eva , Koyi Hirsh , Lewensohn Rolf , De Petris Luigi , Zembutsu Hitoshi , Gréen Henrik 
Published: February 2022

AbstractGemcitabine/carboplatin‐induced myelosuppressive adverse drug reactions (ADRs) are clinical problems leading to patient suffering and dose alterations. There is a need for personalised medicine to improve treatment effects and patients' well‐being. We tested four genetic variants, rs11141915, rs1901440, rs12046844 and rs11719165, previously suggested as potential biomarkers for gemcitabine‐induced leukopenia/neutropenia in Japanese patients, in 213 Swedish gemcitabine/carboplatin‐treated non‐small cell lung cancer (NSCLC) patients. DNA was genotyped using TaqMan probes and real‐time PCR. The relationships between the risk alleles and low toxicity (non‐ADR: Common Terminology Criteria for Adverse Events [CTCAE] grades 0) or high toxicity (ADR: CTCAE grades 3–4) of platelets, leukocytes and neutrophils were evaluated using Fisher's exact test. The risk alleles did not correlate with myelosuppression, and the strongest borderline significance (not withstanding adjustment for multiple testing) was for rs1901440 (neutropenia, p = 0.043) and rs11719165 (leukopenia, p = 0.049) where the risk alleles trended towards lower toxicity, contrasting with previous study findings. Risk alleles and higher risk scores were more common among our patients. We conclude that the genetic variants do not apply to Swedish patients treated with gemcitabine/carboplatin. However, they can still be important in other populations and cohorts, especially in a gemcitabine monotherapy setting, where the causal genetic variation might influence myelosuppressive ADRs.
Effects of Zuojin Pill (Rhizoma CoptidisandFructus Evodiaepreparation) on the pharmacokinetics and side effects of venlafaxine in humans
Authors: Yan Dongmin , Wu Ming , Hu Wenjuan , Li Yue , Jin Jingyi , Yan Shaoqing , Zhu Wei , Ye Chaoyang , Liu Jia , Liu Guobin , Tan Bo 
Published: February 2022

AbstractVenlafaxine (VEN), a first‐line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting ofRhizoma CoptidisandFructus Evodiae, are high likely co‐administered in China. ZJP could significantly inhibit VEN pharmacokinetics in vitro and in rats through suppression of CYP2D6 activity. To date, however, no clinical study has demonstrated the clinical relevance. Here, the VEN pharmacokinetics at a single dose of VEN with or without co‐administration of ZJP was compared. ZJP had a weak herb–drug interactions (HDI) on the pharmacokinetics of VEN. The geometric means ofCmaxand AUC0‐∞of VEN increased by 36.7% and 34.6%, respectively, and the corresponding 90% confidence intervals (CIs) of geometric mean ratios (GMRs) exceed outside bioequivalent range of 0.80–1.25. However, the corresponding 90% CIs of GMRs of these parameters for ODV were within the range. Since ODV exposure (AUC), approximately 3.4‐fold higher than that of VEN, hardly changed, the systemic exposure of VEN active moiety (VEN + ODV) with ZJP increased slightly (≤8.5%) compared with that of VEN alone. In addition, the incidence of VEN‐related side effects, especially gastrointestinal relevance, was significantly reduced with ZJP. Therefore, rational concomitant use of VEN and ZJP might have low risk of HDI and be promising in clinical practice.
Karl and Tilla König and the creation of the Camphill Movement
Authors: Jackson Robin 
Published: February 2022

AbstractThe Camphill Movement is one of the largest independent providers of social care for people with a learning disability: there are 119 communities located throughout the world. From the start, the principal aim of the Movement—co‐founded by Dr. Karl König and his wife Tilla (née Maasberg) in Aberdeen—was to build communities in which children and adults with a learning disability could live, learn, and work with others in healthy social relationships. Karl König was born in Leopoldstadt, Vienna on the 25 September 1902 and died on the 27 March 1966 in a Camphill community in Brachenreuthe, Germany. Mathilde Maasberg was born in Gnadenfrei, Silesia, on the 9 March 1902 and died on the 17 September 1983 in the Camphill community of Fairways in South Africa. The paper focuses primarily on the lives of Karl and Tilla König and highlights the key points in their respective biographies. Whilst it is usually the name of Dr. Karl König that is associated with the Camphill Movement, a case is presented here that his wife significantly shaped the essential character of the Camphill way of life. She had been born into a Moravian Brethren settlement and latterly wove a strong, discernible and enduring element of Moravian practice into the fabric of Camphill life and work. Since the deaths of Karl and Tilla König Camphill communities have continued to seek the creation of environments where the economic, social and spiritual aspects of the community life complement one another. The paper identifies six key constituents that it is argued are central to the essence of Camphillness: mutuality, rhythmicity, spirituality, tranquillity, ecological sensitivity and economic sustainability. The paper ends with reflections on the 21st Century relevance of Camphill communities.
Voices from parents on the sexuality of their child with intellectual disabilities: A socioemotional perspective in a Chinese context
Authors: Lam Angus , Yau Matthew K. , Franklin Richard C. , Leggat Peter A. 
Published: February 2022

AbstractBackgroundThis qualitative study explored the attitudes and experiences of Hong Kong Chinese parents/carers relating to the sexual needs of their child with intellectual disabilities.MethodsSemi‐structured interviews were conducted in Hong Kong with seven parents/carers applying Interpretative Phenomenological Analysis to explore their experiences of and attitudes towards the sexual needs of their adult child with intellectual disabilities.FindingsData revealed three salient variations in participants' attitudes towards the child's sexual needs: concern, reluctance and prohibition. Participants' anxiety about discussing sexuality was evident. Most participants further displayed a layer of feeling that combined ‘love’ and ‘grief’. Based on Goffman's dramaturgical perspective, participants exhibited front stage and back stage behaviours that are believed to be strongly influenced by stigmatisation and collectivist culture.ConclusionVarious levels of intervention to reduce stigma are identified and discussed. This study also highlighted the role of caring professionals in generating awareness of the cultural impact on the family and the need to carefully address the subtle feelings experienced by family members with intellectual disabilities.
‘In the circumstances I think we've all managed really well’ an exploration of the impact of the COVID‐19 restrictions on a Child Development Advisor (Portage) Service
Authors: Higgs Pippa , McElwee Jennifer 
Published: February 2022

AbstractBackgroundThe Child Development Advisor (CDA) (Portage) service provides developmental support to children with significant developmental delays and emotional support for their families through fortnightly home visits. However, the onset of the COVID‐19 pandemic and subsequent restrictions imposed to control its spread prevented services from providing face‐to‐face sessions with families and caregivers, thus removing the CDA (Portage) service's primary means of supporting children and their families. This article aims to explore the impact of those changes on a team of CDAs.MethodsSemi‐structured interviews were conducted with six CDAs representing the CDA (Portage) service within one NHS Health Board.FindingsThe CDAs expressed feeling an initial negative impact of the COVID‐19 restrictions on the service, but in the longer term they noticed a number of positive impacts, including caregiver empowerment and improved working with other professionals.ConclusionDespite having their primary means of providing support removed as part of the COVID‐19 restrictions, the service has been able to adapt to continuously support families and promote child development throughout the pandemic and inadvertently developed a service offer that may be more beneficial for both families and professionals in the future.
Trauma‐specific treatment among individuals with intellectual/developmental disabilities: A case series with progressive counting
Authors: Keesler John M. , McCoy Pamela , Wiltz James 
Published: February 2022

AbstractBackgroundIndividuals with intellectual/developmental disabilities are vulnerable to potentially traumatic events and trauma sequelae. Despite ongoing advances surrounding trauma and intellectual/developmental disabilities, trauma‐specific treatments are needed for people with intellectual/developmental disabilities. This study explores the first implementation of Progressive Counting (PC), a novel trauma treatment, with people with intellectual/developmental disabilities.MethodsA case series with descriptive analyses was used to explore the implementation and effectiveness of PC among four adults with intellectual/developmental disabilities and trauma histories.FindingsPC was associated with reductions in symptoms and increased quality of life. Although individual experiences required modest adaptations to the intervention, PC was generally well‐tolerated and required a limited number of treatment sessions.ConclusionsPC demonstrates promise as a trauma‐specific treatment. Additional research with increased methodological rigor is warranted to further establish its efficacy. Recommendations for future research and practice are provided.
Molecular dynamic and pharmacological studies on protein‐engineered hirudin variants of Hirudinaria manillensis and Hirudo medicinalis
Authors: Sun Yan , Wang Baochun , Pei Jinli , Luo Ying , Yuan Nan , Xiao Zhengpan , Wu Hao , Luo Chenghui , Wang Jiaxuan , Wei Shuangshuang , Pei Yechun , Fu Shengmiao , Wang Dayong 
Published: February 2022

Background and PurposeHirudin variants are the most powerful thrombin inhibitors discovered to date, with a lower risk of bleeding than heparin. For anticoagulation, the C‐termini of hirudin variants bind to the exocite I of thrombin. Anticoagulant effects of gene‐recombinant hirudin are weaker than natural hirudin for the reason of lacking tyrosine O‐sulfation at C‐terminus.Experimental ApproachAn integrative pharmacological study was carried out using molecular dynamic, molecular biological and in vivo and in vitro experiments to elucidate the anticoagulant effects of protein‐engineered hirudins.Key ResultsMolecular dynamic analysis showed that modifications of the C‐termini of hirudin variant 1 of Hirudo medicinalis (HV1) and hirudin variant 2 of Hirudinaria manillensis (HM2) changed the binding energy of the C‐termini to human thrombin. The study indicated that Asp61 of HM2 that corresponds to sulfated Tyr63 of HV1 is critical for inhibiting thrombin activities. Further, the anticoagulant effects of HV1 and HM2 were improved when the amino acid residues adjacent to Asp61 were mutated to Asp. These improvements were prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time of human blood, and decreased Ki and IC50 values. In the in vivo experiments, mutations at C‐termini of HV1 and HM2 significantly changed partial thromboplastin time, prothrombin and thrombin timeConclusion and ImplicationsThe study indicated that the anticoagulant effects of gene‐engineered HM2 are stronger than gene‐engineered HV1 and HM2‐E60D‐I62D has the strongest effects and could be an antithrombotic with better therapeutic effects.
CHIP‐associated mutant ASXL1 in blood cells promotes solid tumor progression
Authors: Liu Xiaoxiao , Sato Naru , Shimosato Yuko , Wang Teh‐Wei , Denda Tamami , Chang Yu‐Hsuan , Yabushita Tomohiro , Fujino Takeshi , Asada Shuhei , Tanaka Yosuke , Fukuyama Tomofusa , Enomoto Yutaka , Ota Yasunori , Sakamoto Takeharu , Kitamura Toshio , Goyama Susumu 
Published: February 2022

AbstractClonal hematopoiesis of indeterminate potential (CHIP) is an age‐associated phenomenon characterized by clonal expansion of blood cells harboring somatic mutations in hematopoietic genes, including DNMT3A, TET2, and ASXL1. Clinical evidence suggests that CHIP is highly prevalent and associated with poor prognosis in solid‐tumor patients. However, whether blood cells with CHIP mutations play a causal role in promoting the development of solid tumors remained unclear. Using conditional knock‐in mice that express CHIP‐associated mutant Asxl1 (Asxl1‐MT), we showed that expression of Asxl1‐MT in T cells, but not in myeloid cells, promoted solid‐tumor progression in syngeneic transplantation models. We also demonstrated that Asxl1‐MT–expressing blood cells accelerated the development of spontaneous mammary tumors induced by MMTV‐PyMT. Intratumor analysis of the mammary tumors revealed the reduced T‐cell infiltration at tumor sites and programmed death receptor‐1 (PD‐1) upregulation in CD8+ T cells in MMTV‐PyMT/Asxl1‐MT mice. In addition, we found that Asxl1‐MT induced T‐cell dysregulation, including aberrant intrathymic T‐cell development, decreased CD4/CD8 ratio, and naïve‐memory imbalance in peripheral T cells. These results indicate that Asxl1‐MT perturbs T‐cell development and function, which contributes to creating a protumor microenvironment for solid tumors. Thus, our findings raise the possibility that ASXL1‐mutated blood cells exacerbate solid‐tumor progression in ASXL1‐CHIP carriers.
Tumor‐penetrating peptide internalizing RGD enhances radiotherapy efficacy through reducing tumor hypoxia
Authors: Meng Fanyan , Liu Jun , Wei Jia , Yang Ju , Zhou Chong , Yan Jing , Liu Baorui 
Published: February 2022

AbstractResistance to irradiation (IR) remains a major therapeutic challenge in tumor radiotherapy. The development of novel tumor‐specific radiosensitizers is crucial for effective radiotherapy against solid tumors. Here, we revealed that remodeling tumor tissue penetration via tumor‐penetrating peptide internalizing arginine–glycine–aspartic acid RGD (iRGD) enhanced irradiation efficacy. The growth of 4T1 and CT26 multicellular tumor spheroids (MCTS) and tumors was delayed significantly by the treatment with IR and iRGD. Mechanistically, iRGD reduced hypoxia in MCTS and tumors, resulting in enhanced apoptosis after MCTS and tumors were treated with IR and iRGD. This is the first report that shows enhanced radiation efficacy by remodeling tumor‐specific tissue penetration with iRGD, implying the potential clinical application of peptides in future tumor therapy.
Twelve‐month evaluation of a novel mineral–organic adhesive material used to stabilize dental implants placed in oversized osteotomies in vivo in an animal model
Authors: Cochran David L. , Jones Archie A. , Sugita Ryushiro , Brown Michael C. , Prasad Hari , Kay George W. 
Published: February 2022

AbstractObjectivesThe aim of this study is to evaluate long‐term in vivo stability of dental implants stabilized at time of placement in oversized osteotomies with a novel, self‐setting, mineral–organic bone adhesive.Materials/MethodsCanine (26) mandibular teeth were removed, and three oversized osteotomies prepared bilaterally. Implants were placed with either adhesive, particulate xenograft, or with blood clot filling the implant/osteotomy gaps. Removal torque and histology were assessed.ResultsThe adhesive provided significant and clinically relevant immediate implant stability of 22.2 N‐cm (95% CI 5.3; 39.0), which continued throughout the early postoperative course and persisted through the nine‐ (155 N‐cm 95% CI 113; 197) and 12‐month (171 N‐cm 95% CI 134.2; 209.4) time points. This is in comparison with the blood clot of 1.4 N‐cm (95% CI 0.7; 2.1), 128.6 N‐cm (95% CI 66.8; 190.4), and 140.7 N‐cm (95% CI 78.8; 202.5) and particulate xenograft, 1.3 N‐cm (95% CI 0.6; 2.0), 132.1 N‐cm (95% CI 94.5; 169.7), and 101.5 (95% CI 59.5; 143.5), respectively. Histological examination shows the adhesive establishes intimate contact with the implant and bony walls and is replaced with new bone without compromising stability. Soft tissue does not penetrate the adhesive, and marginal bone/biomaterial level is maintained. Control sites filled with xenograft or blood clot heal with reduced bone levels, and in some cases, xenograft particles were encapsulated in connective tissue.ConclusionsImplants placed in oversized osteotomies and lacking primary stability can be stabilized at placement with a novel, highly osteoconductive, and resorbable adhesive. Gradual replacement of the biomaterial allows osseointegration without loss of stability through 12 months of follow‐up. This novel adhesive has the potential to stabilize implants placed in sites with inadequate bony support.