bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol and Feasibility-Randomized Trial of Telehealth Delivery for a Multicomponent Upper Extremity Intervention in Infants With Asymmetric Cerebral Palsy
Authors: Pietruszewski Lindsay , Burkhardt Stephanie , Yoder Paul J. , Heathcock Jill , Lewandowski Dennis J. , Maitre Nathalie L. 
Published: September 2020

Background: Past work showed that an in-person, therapist-guided, parent-implemented multicomponent intervention increased the motor functioning of the more affected upper extremity (UE) in infants with asymmetric cerebral palsy. The authors document treatment fidelity and provide initial testing of telehealth intervention delivery in a new subject sample. Methods: The authors adapted the intervention manual used in the previous trial for telehealth. Infants (6-24 months) were randomly assigned to intervention (n = 7) or waitlist (n = 6). The intervention prescribed soft-constraint wear on the less affected UE for 6 hours, 5 d/wk, and exercises. After an initial in-person training session, three 15- to 45-minute telehealth sessions were performed. Results: Median weekly constraint wear was 21 hours (interquartile range = 10.3-29.7); average parent-treatment fidelity was 95.7% (SD 11.2). A significant large (Cohen d = 0.92) between-group differences occurred on fine motor functioning of more affected UEs. Conclusion: The telehealth intervention was feasible and potentially effective, but a larger trial is needed to evaluate efficacy.
piRNA-30473 contributes to tumorigenesis and poor prognosis by regulating m6A RNA methylation in DLBCL
Authors: Han Huiying , Fan Gao , Song Sha , Jiang Yunxin , Qian Chen'ao , Zhang Weimin , Su Qi , Xue Xiaofeng , Zhuang Wenzhuo , Li Bingzong 
Published: September 2020

Abstract
The initiation and progression of diffuse large B-cell lymphoma (DLBCL) is governed by genetic and epigenetic aberrations. As the most abundant eukaryotic messenger RNA (mRNA) modification, N6-methyladenosine (m6A) is known to influence various fundamental bioprocesses by regulating the target gene; however, the function of m6A modifications in DLBCL is unclear. PIWI-interacting RNAs (piRNAs) have been indicated to be epigenetic effectors in cancer. Here, we show that high expression of piRNA-30473 supports the aggressive phenotype of DLBCL, and piRNA-30473 depletion decreases proliferation and induces cell cycle arrest in DLBCL cells. In xenograft DLBCL models, piRNA-30473 inhibition reduces tumor growth. Moreover, piRNA-30473 is significantly associated with overall survival in a univariate analysis and is statistically significant after adjusting for the National Comprehensive Cancer Network-International Prognostic Index in the multivariate analysis. Additional studies demonstrate that piRNA-30473 exerts its oncogenic role through a mechanism involving the upregulation of WTAP, an m6A mRNA methylase, and thus enhances the global m6A level. Integrating transcriptome and m6A-sequencing analyses reveals that WTAP increases the expression of its critical target gene, hexokinase 2 (HK2), by enhancing the HK2 m6A level, thereby promoting the progression of DLBCL. Together, the piRNA-30473/WTAP/HK2 axis contributes to tumorigenesis by regulating m6A RNA methylation in DLBCL. Furthermore, by comprehensively analyzing our clinical data and data sets, we discover that the m6A regulatory genes piRNA-30473 and WTAP improve survival prediction in DLBCL patients. Our study highlights the functional importance of the m6A modification in DLBCL and might assist in the development of a prognostic stratification and therapeutic approach for DLBCL.
Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies
Authors: Gauthier Jordan , Bezerra Evandro D. , Hirayama Alexandre V. , Fiorenza Salvatore , Sheih Alyssa , Chou Cassie K. , Kimble Erik L. , Pender Barbara S. , Hawkins Reed M. , Vakil Aesha , Phi Tinh-Doan , Steinmetz Rachel N. , Jamieson Abby W. , Bar Merav , Cassaday Ryan D. , Chapuis Aude G. , Cowan Andrew J. , Green Damian J. , Kiem Hans-Peter , Milano Filippo , Shadman Mazyar , Till Brian G. , Riddell Stanley R. , Maloney David G. , Turtle Cameron J. 
Published: September 2020

Abstract
CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy has shown significant efficacy for relapsed or refractory (R/R) B-cell malignancies. Yet, CD19 CAR T cells fail to induce durable responses in most patients. Second infusions of CD19 CAR T cells (CART2) have been considered as a possible approach to improve outcomes. We analyzed data from 44 patients with R/R B-cell malignancies (acute lymphoblastic leukemia [ALL], n = 14; chronic lymphocytic leukemia [CLL], n = 9; non-Hodgkin lymphoma [NHL], n = 21) who received CART2 on a phase 1/2 trial (NCT01865617) at our institution. Despite a CART2 dose increase in 82% of patients, we observed a low incidence of severe toxicity after CART2 (grade ≥3 cytokine release syndrome, 9%; grade ≥3 neurotoxicity, 11%). After CART2, complete response (CR) was achieved in 22% of CLL, 19% of NHL, and 21% of ALL patients. The median durations of response after CART2 in CLL, NHL, and ALL patients were 33, 6, and 4 months, respectively. Addition of fludarabine to cyclophosphamide-based lymphodepletion before the first CAR T-cell infusion (CART1) and an increase in the CART2 dose compared with CART1 were independently associated with higher overall response rates and longer progression-free survival after CART2. We observed durable CAR T-cell persistence after CART2 in patients who received cyclophosphamide and fludarabine (Cy-Flu) lymphodepletion before CART1 and a higher CART2 compared with CART1 cell dose. The identification of 2 modifiable pretreatment factors independently associated with better outcomes after CART2 suggests strategies to improve in vivo CAR T-cell kinetics and responses after repeat CAR T-cell infusions, and has implications for the design of trials of novel CAR T-cell products after failure of prior CAR T-cell immunotherapies.
Why physical activity matters for older adults in a time of pandemic
Authors: Cunningham Conor , O’ Sullivan Roger 
Published: September 2020

Abstract
Background
The COVID-19 pandemic has impacted communities across the world. Government responses, of promoting ‘social distancing’ at a population level, and ‘self-isolation’ of older adults to mitigate its spread have been unprecedented. Despite the importance of these Public Health and Social Measures (PHSM), they present challenges to maintaining a physically active lifestyle, particularly for older adults.

Context
The importance of physical activity (PA) for health is well documented. There is strong evidence that PA in later life reduces the risk of disease, helps to manage existing conditions, and develops and maintains physical and mental function. Staying physically active is particularly important for older adults currently.

Implications and recommendations
Research suggests that PHSM have already reduced levels of PA for older adults during the COVID-19 pandemic. Prior to COVID-19 many older adults were not engaging in enough PA to attain health benefits. Evidence indicates that there will be an increase in the number of older adults not meeting guidelines for PA due to the impacts of COVID-19. This has implications for population health and public health policy. How to support older adults to remain physically active during and after the COVID-19 crisis will require careful consideration. Going forward it is imperative that policy and practice support all older adults to achieve the recommended levels of PA to ensure that they are not disadvantaged in the short- but also in the longer term by the impact of COVID-19.
Food intake biomarkers for berries and grapes
Authors: Ulaszewska M. , Garcia-Aloy M. , Vázquez-Manjarrez N. , Soria-Florido M. T. , Llorach R. , Mattivi F. , Manach C. 
Published: September 2020

AbstractGrapes and berries are two types of widely consumed fruits characterized by a high content in different phytochemicals. However, their accurate dietary assessment is particularly arduous, because of the already wide recognized bias associated with self-reporting methods, combined with the large range of species and cultivars and the fact that these fruits are popularly consumed not only in fresh and frozen forms but also as processed and derived products, including dried and canned fruits, beverages, jams, and jellies. Reporting precise type and/or quantity of grape and berries in FFQ or diaries can obviously be affected by errors. Recently, biomarkers of food intake (BFIs) rose as a promising tool to provide accurate information indicating consumption of certain food items. Protocols for performing systematic reviews in this field, as well as for assessing the validity of candidate BFIs have been developed within the Food Biomarker Alliance (FoodBAll) Project. This paper aims to evaluate the putative BIFs for blueberries, strawberries, raspberries, blackberries, cranberries, blackcurrant, and grapes. Candidate BFIs for grapes were resveratrol metabolites and tartaric acid. The metabolites considered as putative BFI for berries consumption were mostly anthocyanins derivatives together with several metabolites of ellagitannins and some aroma compounds. However, identification of BFIs for single berry types encountered more difficulties. In the absence of highly specific metabolites reported to date, we suggested some multi-metabolite panels that may be further investigated as putative biomarkers for some berry fruits.
Metabolic and transcriptome responses of RNAi-mediated AMPKα knockdown in Tribolium castaneum
Authors: Jiang Heng , Zhang Nan , Ji Caihong , Meng Xiangkun , Qian Kun , Zheng Yang , Wang Jianjun 
Published: September 2020

Abstract
Background
The AMP-activated protein kinase (AMPK) is an intracellular fuel sensor for lipid and glucose metabolism. In addition to the short-term regulation of metabolic enzymes by phosphorylation, AMPK may also exert long-term effects on the transcription of downstream genes through the regulation of transcription factors and coactivators. In this study, RNA interference (RNAi) was conducted to investigate the effects of knockdown of TcAMPKα on lipid and carbohydrate metabolism in the red flour beetle, Tribolium castaneum, and the transcriptome profiles of dsTcAMPKα-injected and dsEGFP-injected beetles under normal conditions were compared by RNA-sequencing.

Results
RNAi-mediated suppression of TcAMPKα increased whole-body triglyceride (TG) level and the ratio between glucose and trehalose, as was confirmed by in vivo treatment with the AMPK-activating compound, 5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside (AICAR). A total of 1184 differentially expressed genes (DEGs) were identified between dsTcAMPKα-injected and dsEGFP-injected beetles. These include genes involved in lipid and carbohydrate metabolism as well as insulin/insulin-like growth factor signaling (IIS). Real-time quantitative polymerase chain reaction analysis confirmed the differential expression of selected genes. Interestingly, metabolism-related transcription factors such as sterol regulatory element-binding protein 1 (SREBP1) and carbohydrate response element-binding protein (ChREBP) were also significantly upregulated in dsTcAMPKα-injected beetles.

Conclusions
AMPK plays a critical role in the regulation of beetle metabolism. The findings of DEGs involved in lipid and carbohydrate metabolism provide valuable insight into the role of AMPK signaling in the transcriptional regulation of insect metabolism.
Mortality in severely injured patients: nearly one of five non-survivors have been already discharged alive from ICU
Authors: Hamsen Uwe , Drotleff Niklas , Lefering Rolf , Gerstmeyer Julius , Schildhauer Thomas Armin , Waydhas Christian ,   TraumaRegister DGU 
Published: September 2020

Abstract
Background
Most trauma patients admitted to the hospital alive and die later on, decease during the initial care in the emergency department or the intensive care unit (ICU). However, a number of patients pass away after having been discharged from the ICU during the initial hospital stay. On first sight these cases could be seen as “failure to rescue” of potentially salvageable patients. A low rate of such patients might be a potential indicator of quality for trauma care on ICUs and surgical wards.

Methods
Retrospective analysis of the TraumaRegister DGU® with data from 2015 to 2017. Patients that died during the initial ICU stay were compared to those who were discharged from the initial ICU stay for at least 24 h but died later on.

Results
A total of 82,313 trauma patients were included in the TraumaRegister DGU®. In total, 6576 patients (8.0%) died during their hospital stay. Out of those, 5481 were admitted to the ICU alive and 972 patients (17.7%) were discharged from ICU and died later on. Those were older (mean age: 77 vs. 68 years), less severely injured (mean ISS: 23.1 vs. 30.0 points) and had a longer mean ICU length of stay (10 vs. 6 days). A limitation of life-sustaining therapy due to a documented living will was present in 46.1% of all patients who died during their initial ICU stay and in 59.9% of patients who died after discharge from their initial ICU stay.

Conclusions
17.7% of all non-surviving severely injured trauma patients died within the hospital after discharge from their initial ICU treatment. Their death can partially be explained by a limitation of therapy due to a living will. In conclusion, the rate of such late deaths may partially represent patients that died of potentially avoidable or treatable complications.
Assessing risk of bias: a proposal for a unified framework for observational studies and randomized trials
Authors: Luijendijk Hendrika J. , Page Matthew J. , Burger Huibert , Koolman Xander 
Published: September 2020

Abstract
Background
Evidence based medicine aims to integrate scientific evidence, clinical experience, and patient values and preferences. Individual health care professionals need to appraise the evidence from randomized trials and observational studies when guidelines are not yet available. To date, tools for assessment of bias and terminologies for bias are specific for each study design. Moreover, most tools appeal only to methodological knowledge to detect bias, not to subject matter knowledge, i.e. in-depth medical knowledge about a topic. We propose a unified framework that enables the coherent assessment of bias across designs.

Methods
Epidemiologists traditionally distinguish between three types of bias in observational studies: confounding, information bias, and selection bias. These biases result from a common cause, systematic error in the measurement or common effect of the intervention and outcome respectively. We applied this conceptual framework to randomized trials and show how it can be used to identify bias. The three sources of bias were illustrated with graphs that visually represent researchers’ assumptions about the relationships between the investigated variables (causal diagrams).

Results
Critical appraisal of evidence started with the definition of the research question in terms of the population of interest, the compared interventions and the main outcome. Next, we used causal diagrams to illustrate how each source of bias can lead to over- or underestimated treatment effects. Then, we discussed how randomization, blinded outcome measurement and intention-to-treat analysis minimize bias in trials. Finally, we identified study aspects that can only be appraised with subject matter knowledge, irrespective of study design.

Conclusions
The unified framework encompassed the three main sources of bias for the effect of an assigned intervention on an outcome. It facilitated the integration of methodological and subject matter knowledge in the assessment of bias. We hope that graphical diagrams will help clarify debate among professionals by reducing misunderstandings based on different terminology for bias.
Advance care planning with people with dementia: a process evaluation of an educational intervention for general practitioners
Authors: Tilburgs Bram , Koopmans Raymond , Schers Henk , Smits Carolien , Vernooij-Dassen Myrra , Perry Marieke , Engels Yvonne 
Published: September 2020

Abstract
Background
General practitioners (GPs) are advised to offer advance care planning (ACP) to people with dementia (PWD). In a randomized controlled trial, an educational intervention for GPs aimed at initiating and optimizing ACP proved to be effective. During the intervention most GPs were accompanied by their practice nurse (PN). To provide insights into the intervention’s successful components and what could be improved, we conducted a process evaluation and explored implementation, mechanisms of impact and contextual factors.

Methods
We used the Medical Research Council guidance for process evaluations. Implementation was explored identifying reach and acceptability. We performed descriptive analyses of participants’ characteristics; selection, inclusion and intervention attendance; a GP post-intervention survey on initiating ACP; a post intervention focus group with trainers of the intervention.
Mechanisms of impact were explored identifying adoption and appropriateness. We used: participants’ intervention ratings; a GP post-intervention survey on conducting ACP; ACP documentation in PWD’s medical files; post-intervention interviews with PWD/FC dyads. All data was used to identify contextual factors.

Results
The intervention was implemented by a small percentage of the total Dutch GP population invited, who mostly included motivated PWD/FC dyads with relatively little burden, and PWD with limited cognitive decline. The mechanisms of impact for GPs were: interactively learning to initiate ACP with training actors with a heterogeneous group of GPs and PNs. For PWD/FCs dyads, discussing non-medical preferences was most essential regarding their SDM experience and QoL. Some dyads however found ACP stressful and not feasible. Younger female GPs more often initiated ACP. Male PWD and those with mild dementia more often had had ACP. These characteristics and the safe and intimate training setting, were important contextual facilitators.

Conclusion
We recommend Interventions aimed at improving ACP initiation with PWD by GPs to include interactive components and discussion of non-medical preferences. A safe environment and a heterogeneous group of participants facilitates such interventions. However, in practice not all FC/PWD dyads will be ready to start. Therefore, it is necessary to check their willingness when ACP is offered.
Reducing caesarean section rate in an urban hospital serving women attending privately in India – a quality improvement initiative
Authors: Bhartia Abhishek , Sen Gupta Dhar Rinku , Bhartia Saru 
Published: September 2020

Abstract
Background
In line with global trends, India has witnessed a sharp rise in caesarean section (CS) deliveries, especially in the private sector. Despite the urgent need for change, there are few published examples of private hospitals that have successfully lowered their CS rates. Our hospital, serving private patients too, had a CS rate of 79% in 2001. Care was provided by fee-for-service visiting consultant obstetricians without uniform clinical protocols and little clinical governance. Consultants attributed high CS rate to case-mix and maternal demand and showed little inclination for change. We attempted to reduce this rate with the objective of improving the quality of our care and demonstrating that CS could be safely lowered in the private urban Indian healthcare setting.

Methods
We hired full-time salaried consultants and began regular audit of CS cases. When this proved inadequate, we joined an improvement collaborative in 2011 and dedicated resources for quality improvement. We adopted practice guidelines, monitored outcomes by consultant, improved labour ward support, strengthened antenatal preparation, and moved to group practice among consultants.

Results
Guidelines ensured admissions in active labour and reduced CS (2011 to 2016) for foetal heart rate abnormalities (23 to 5%; p < 0.001) and delayed progress (19 to 6%; p < 0.001) in low-risk first-birth women. Antenatal preparation increased trial of labour, even among women with prior CS (28 to 79%; p < 0.001). Group practice reduced time pressure and stress, with a decline in CS (52 to 18%; p < 0.001) and low-risk first-birth CS (48 to 12%; p < 0.001). Similar CS rates were maintained in 2017 and 2018. Measures of perinatal harm including post-partum haemorrhage, 3rd-4th degree tears, shoulder dystocia, and Apgar < 7 at 5 min were within acceptable ranges (13, 3, 2% and 3 per thousand respectively in 2016–18,).

Conclusions
It is feasible to substantially reduce CS rate in private healthcare setting of a middle-income country like India. Ideas such as moving to full-time attachment of consultants, joining a collaborative, improving labour ward support, providing resources for data collection, and perseverance could be adopted by other hospitals in their own journey of moving towards a medically justifiable CS rate.
Which is better for mothers and babies: fresh or frozen-thawed blastocyst transfer?
Authors: Yang Meiling , Lin Li , Sha Chunli , Li Taoqiong , Gao Wujiang , Chen Lu , Wu Ying , Ma Yanping , Zhu Xiaolan 
Published: September 2020

AbstractBackgroundIn recent years, there have been many reports on the pregnancy outcomes of fresh blastocyst transfer (BT) and frozen-thawed BT, but the conclusions are controversial and incomplete. To compare the pregnancy outcomes, maternal complications and neonatal outcomes of fresh and frozen-thawed BT in the context of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles, we conducted a meta-analysis.MethodsA meta-analysis was conducted by searching the PubMed, Embase, and Cochrane Library databases through May 2020. Data were extracted independently by two authors.ResultsFifty-four studies, including 12 randomized controlled trials (RCTs), met the inclusion criteria. Fresh BT was associated with a lower implantation rate, pregnancy rate, ongoing pregnancy rate, and clinical pregnancy rate and higher ectopic pregnancy rate than frozen-thawed BT according to the results of the RCTs. The risks of moderate or severe ovarian hyperstimulation syndrome, placental abruption, placenta previa and preterm delivery were higher for fresh BT than for frozen-thawed BT. The risk of pregnancy-induced hypertension and pre-eclampsia was lower for fresh BT; however, no significant differences in risks for gestational diabetes mellitus and preterm rupture of membrane were found between the two groups. Compared with frozen-thawed BT, fresh BT appears to be associated with small for gestational age and low birth weight. No differences in the incidences of neonatal mortality or neonatal malformation were observed between fresh and frozen-thawed BT.ConclusionsAt present there is an overall slight preponderance of risks in fresh cycles against frozen, however individualization is required and current knowledge does not permit to address a defintive response.