bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of adiponectin and leptin signaling-related microRNAs in the preventive effects of calorie restriction in mammary tumor development
Authors: Dogan Soner , Cicekdal Munevver B. , Ozorhan Umit , Karabiyik Goktug , Kazan Busra T. , Ekici Isin D. , Yilmaz Bayram , Demirel Pinar B. , Coban Ilker , Tuysuz Emre Can , Kuskucu Aysegul , Bayrak Omer F. , Cleary Margot P. , Tuna Bilge G. 
Published: January 2021

Calorie restriction (CR) is suggested to prevent the development of mammary tumors (MTs); however, the mechanism remains to be clarified. We aimed to determine the microRNA (miRNA) profile in mice applied to 2 different CR protocols; chronic (CCR) and intermittent (ICR) and follow the MT development. In addition, the roles of miRNAs involved in adiponectin and/or leptin signaling pathways were investigated. Mice were divided into 3 groups: ad-libitum (AL), CCR, or ICR, which comprised 3 weeks of AL feeding followed by 1 week of 60% CR in a cyclic manner. Blood and tissue collection were performed at weeks 10, 17/18, 49/50 and 81/82. Long-term CCR provided better protection compared with ICR for MT development with a delay in the MT occurrence. Adiponectin expression in mammary fat pad were significantly higher in CCR group compared with AL. Using GeneChip Array, 250 of 3195 miRNAs were differentially expressed among the dietary groups. Thirteen of 250 miRNAs were related to adiponectin and/or leptin signaling genes. Results were verified by reverse transcription polymerase chain reaction. Specifically, miR-326-3p, miR-500-3p and miR-129-5p, which are related to adiponectin and/or leptin signaling, may play important roles in the preventive effects of CR in MT development and in ageing. Thus, these miRNAs might be putative biomarkers to target for diagnostic and treatment purposes. Novelty: Type of CR and micro RNA interaction is related to ageing. miR-326-3p, miR-500-3p and miR-129-5p expression levels were differentially expressed in MT development and in ageing. The genes associated with adiponectin and/or leptin signaling pathways are regulated by certain miRNAs in the protective effects of CR.
A ground-state complex between methyl viologen and the fluorescent whitening agent 4,4′-bis(2-sulfostyryl)-biphenyl disodium salt: a fluorescence spectroscopy study
Authors: Armstrong Emily J. , Galas Henry , Wylie R. Stephen , Zohrehvand Shiva , Stam Jan van , Evans Christopher H. 
Published: January 2021

This study explores the quenching of the dianionic fluorescent whitening agent, NFW, by various substances, including methyl viologen (MV), in water and in the presence of beta-cyclodextrin (β-CD). Results of a fluorescence spectroscopic examination of the β-CD–NFW system are presented. It was found that NFW forms a 1:1 inclusion complex with β-CD with an association constant of 2540 ± 380 M−1. The included NFW fluorescent state is protected by the β-CD cavity from a range of water-based quenchers (neutral, anionic, and cationic). Quenching proceeds near the diffusion-controlled limit in water for the quenchers tested with the exception of the dicationic MV. Methyl viologen is an extremely efficient quencher of NFW fluorescence with a nominal K SV ∼ 5.0 × 103 M−1 in water alone, corresponding to a nominal k q of ∼ 4 × 1012 M−1 s−1, which exceeds the diffusion-controlled limit in this solvent. The quenching efficiency of MV is strongly suppressed in the presence of 10 mM β-CD (K SV = 105 ± 12 M−1) and in the presence of NaCl (K SV = 106 ± 9 M−1 at 0.5 M salt). In the absence of CD or salt, there is a strong contribution from static quenching in the MV system; the presence of these additives suppresses the static quenching. Various results suggest the static quenching is due to formation of a ground-state complex between the dianion NFW and the dication MV.
Issues arise when time goes digital
Authors: Hill Robin K. 
Published: January 2021

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
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Robin K. Hill considers why time can be "a pesky problem for computing."
Preclinical Evaluation and Phase Ib Study of Prexasertib, a CHK1 Inhibitor, and Samotolisib (LY3023414), a Dual PI3K/mTOR Inhibitor
Authors: Hong David S. , Moore Kathleen N. , Bendell Johanna C. , Karp Daniel D. , Wang Judy S. , Ulahannan Susanna V. , Jones Suzanne , Wu Wenjuan , Donoho Gregory P. , Ding Yan , Capen Andrew , Wang Xuejing , Bence Lin Aimee , Patel Manish R. 
Published: January 2021

AbstractPurpose:Prexasertib, a checkpoint kinase 1 inhibitor (CHK1), exhibited modest monotherapy antitumor activity in previous studies. Preclinical data were generated to support the clinical combination of prexasertib + samotolisib, a PI3K/mTOR inhibitor.Patients and Methods:Prexasertib + samotolisib was first evaluated in triple-negative breast cancer (TNBC) cells, MDA-MB-231 orthotopic xenograft tumors, and TNBC patient–derived xenograft (PDX) mouse models. In the phase Ib trial, following dose escalation, the initial expansion arm (E1, solid tumors) explored prexasertib 105 mg/m2 intravenously every 14 days + samotolisib 200 mg orally twice daily. Subsequent expansion arms evaluated samotolisib 150 mg twice daily in patients carrying PIK3CA mutations (E2, solid tumors) or with TNBC (E3). Safety and antitumor activity were assessed.Results:Prexasertib + samotolisib inhibited cell proliferation in TNBC lines and primary tumor growth in the MDA-MB-231 model. Prexasertib + samotolisib exhibited synergistic or additive effects in 30 of 38 PDX single-mouse (“n = 1”) models, and provided rationale for clinical evaluation. In the phase Ib study, 53 patients were enrolled (escalation, n = 13; E1, n = 9; E2, n = 15; and E3, n = 16). No dose-limiting toxicities (DLT) were observed during escalation; however, DLT-equivalent toxicities were observed in E1, leading to samotolisib dose reduction (150 mg twice daily) in E2/E3. Common treatment-related adverse events were leukopenia/neutropenia (94.3%), thrombocytopenia (62.3%), and nausea (52.8%). During escalation, 2 patients achieved partial response for an overall response rate (ORR) of 15.4%, and ORRs were 13.3% for E2 (PIK3CA) and 25% for E3 (TNBC).Conclusions:Prexasertib + samotolisib showed antitumor activity in preclinical models and preliminary efficacy in heavily pretreated patients. The clinical combination was associated with toxicity, suggesting supportive measures may be required. However, these data may inform future trials using other CHK1 and PI3K pathway inhibitors.
Abiraterone Acetate Induces CREB1 Phosphorylation and Enhances the Function of the CBP-p300 Complex, Leading to Resistance in Prostate Cancer Cells
Authors: Pan Wenting , Zhang Zhouwei , Kimball Hannah , Qu Fangfang , Berlind Kyler , Stopsack Konrad H. , Lee Gwo-Shu Mary , Choueiri Toni K. , Kantoff Philip W. 
Published: January 2021

Abstract

Purpose:
Abiraterone acetate (AA), an inhibitor of cytochrome P450 17alpha-hydroxylase/17, 20 lyase, is an FDA-approved drug for advanced prostate cancer. However, not all patients respond to AA, and AA resistance ultimately develops in patients who initially respond. We aimed to identify AA resistance mechanisms in prostate cancer cells.

Experimental Design:
We established several AA-resistant cell lines and performed a comprehensive study on mechanisms involved in AA resistance development. RNA sequencing and phospho-kinase array screenings were performed to discover that the cAMP-response element CRE binding protein 1 (CREB1) was a critical molecule in AA resistance development.

Results:
The drug-resistant cell lines are phenotypically stable without drug selection, and exhibit permanent global gene expression changes. The phosphorylated CREB1 (pCREB1) is increased in AA-resistant cell lines and is critical in controlling global gene expression. Upregulation of pCREB1 desensitized prostate cancer cells to AA, while blocking CREB1 phosphorylation resensitized AA-resistant cells to AA. AA treatment increases intracellular cyclic AMP (cAMP) levels, induces kinases activity, and leads to the phosphorylation of CREB1, which may subsequently augment the essential role of the CBP/p300 complex in AA-resistant cells because AA-resistant cells exhibit a relatively higher sensitivity to CBP/p300 inhibitors. Further pharmacokinetics studies demonstrated that AA significantly synergizes with CBP/p300 inhibitors in limiting the growth of prostate cancer cells.

Conclusions:
Our studies suggest that AA treatment upregulates pCREB1, which enhances CBP/p300 activity, leading to global gene expression alterations, subsequently resulting in drug resistance development. Combining AA with therapies targeting resistance mechanisms may provide a more effective treatment strategy.
Reality-Assisted Evolution of Soft Robots through Large-Scale Physical Experimentation: A Review
Authors: Howison Toby , Hauser Simon , Hughes Josie , Iida Fumiya 
Published: January 2021

Abstract
We introduce the framework of reality-assisted evolution to summarize a growing trend towards combining model-based and model-free approaches to improve the design of physically embodied soft robots. In silico, data-driven models build, adapt, and improve representations of the target system using real-world experimental data. By simulating huge numbers of virtual robots using these data-driven models, optimization algorithms can illuminate multiple design candidates for transference to the real world. In reality, large-scale physical experimentation facilitates the fabrication, testing, and analysis of multiple candidate designs. Automated assembly and reconfigurable modular systems enable significantly higher numbers of real-world design evaluations than previously possible. Large volumes of ground-truth data gathered via physical experimentation can be returned to the virtual environment to improve data-driven models and guide optimization. Grounding the design process in physical experimentation ensures that the complexity of virtual robot designs does not outpace the model limitations or available fabrication technologies. We outline key developments in the design of physically embodied soft robots in the framework of reality-assisted evolution.
Jane Austen
Authors: Bartlett Nora 
Published: January 2021

This volume presents an exhilarating and insightful collection of essays on Jane Austen – distilling the author’s deep understanding and appreciation of Austen’s works across a lifetime. The volume is both intra- and inter-textual in focus, ranging from perceptive analysis of individual scenes to the exploration of motifs across Austen’s fiction.
Full of astute connections, these lively discussions hinge on the study of human behaviour – from family relationships to sickness and hypochondria – highlighting Austen’s artful literary techniques and her powers of human observation.
Jane Austen: Reflections of a Reader by (the late) Nora Bartlett is a brilliant contribution to the field of Jane Austen studies, both in its accessible style (which preserves the oral register of the original lectures), and in its foregrounding of the reader in a warm, compelling and incisive conversation about Austen’s works. As such, it will appeal widely to all lovers of Jane Austen, whether first-time readers, students or scholars.
An observational feasibility study - does early limb ergometry affect oxygen delivery and uptake in intubated critically ill patients – a comparison of two assessment methods
Authors: Wilkinson Olive M , Bates Andrew , Cusack Rebecca 
Published: January 2021

Abstract
Background
Early rehabilitation can reduce ventilation duration and improve functional outcomes in critically ill patients. Upper limb strength is associated with ventilator weaning. Passive muscle loading may preserve muscle fibre function, help recover peripheral muscle strength and improve longer term, post-hospital discharge function capacity. The physiological effects of initiating rehabilitation soon after physiological stabilisation of these patients can be concerning for clinicians. This study investigated the feasibility of measuring metabolic demand and the safety and feasibility of early upper limb passive ergometry. An additional comparison of results, achieved from simultaneous application of the methods, is reported.

Methods
This was an observational feasibility study undertaken in an acute teaching hospital’s General Intensive Care Unit in the United Kingdom. Twelve haemodynamically stable, mechanically ventilated patients underwent 30 minutes of arm ergometry. Cardiovascular and respiratory parameters were monitored. A Friedman test identified changes in physiological parameters. A metabolic cart was attached to the ventilator to measure oxygen uptake. Oxygen uptake was concurrently calculated by the reverse Fick method, utilising cardiac output from the LiDCO™ and paired mixed venous and arterial samples. A comparison of the two methods was made. Data collection began 10 minutes before ergometry and continued to recovery. Paired mixed venous and arterial samples were taken every 10 minutes.

Results
Twelve patients were studied; 9 male, median age 55 years, range (27–82), median APACHE score 18.5, range (7–31), median fraction inspired oxygen 42.5%, range (28–60). Eight patients were receiving noradrenaline. Mean dose was 0.07 mcg/kg/min, range (0.01–0.15). Early ergometry was well tolerated. There were no clinically significant changes in respiratory, haemodynamic or metabolic variables pre ergometry to end recovery. There was no significant difference between the two methods of calculating VO2 (p = 0.70).

Conclusions
We report the feasibility of using the reverse Fick method and indirect calorimetry to measure metabolic demand during early physical rehabilitation of critically ill patients. More research is needed to ascertain the most reliable method. Minimal change in metabolic demand supports the safety and feasibility of upper limb ergometry. These results will inform future study designs for further research into exercise response in critically ill patients.

Trial Registration
Clinicaltrials.gov No. NCT04383171. Registered on 06 May 2020 - Retrospectively registered. http://www.clinicaltrials.gov.
Cut-off points between pain intensities of the postoperative pain using receiver operating characteristic (ROC) curves
Authors: Cho Sooyoung , Kim Youn Jin , Lee Minjin , Woo Jae Hee , Lee Hyun Jung 
Published: January 2021

Abstract
Background
Pain assessment and management are important in postoperative circumstances as overdosing of opioids can induce respiratory depression and critical consequences. We aimed this study to check the reliability of commonly used pain scales in a postoperative setting among Korean adults. We also intended to determine cut-off points of pain scores between mild and moderate pain and between moderate and severe pain by which can help to decide to use pain medication.

Methods
A total of 180 adult patients undergoing elective non-cardiac surgery were included. Postoperative pain intensity was rated with a visual analog scale (VAS), numeric rating scale (NRS), faces pain scale revised (FPS-R), and verbal rating scale (VRS). The VRS rated pain according to four grades: none, mild, moderate, and severe. Pain assessments were performed twice: when the patients were alert enough to communicate after arrival at the postoperative care unit (PACU) and 30 min after arrival at the PACU. The levels of agreement among the scores were evaluated using intraclass correlation coefficients (ICCs). The cut-off points were determined by receiver operating characteristic curves.

Results
The ICCs among the VAS, NRS, and FPS-R were consistently high (0.839–0.945). The pain categories were as follow: mild ≦ 5.3 / moderate 5.4 ~ 7.1 /severe ≧ 7.2 in VAS, mild ≦ 5 / moderate 6 ~ 7 / severe ≧ 8 in NRS, mild ≦ 4 / moderate 6 / severe 8 and 10 in FPS-R. The cut-off points for analgesics request were VAS ≧ 5.5, NRS ≧ 6, FPS-R ≧ 6, and VRS ≧ 2 (moderate or severe pain).

Conclusions
During the immediate postoperative period, VAS, NRS, and FPS-R were well correlated. The boundary between mild and moderate pain was around five on 10-point scales, and it corresponded to the cut-off point of analgesic request. Healthcare providers should consider VRS and other patient-specific signs to avoid undertreatment of pain or overdosing of pain medication.
Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) may be safe for COVID-19 patients
Authors: Wang Wenjun , Zhao Xiaohui , Wei Wei , Fan Weiwang , Gao Kai , He Shengxiu , Zhuang Xijing 
Published: January 2021

Abstract
Background
To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) administration to hypertension patients with the coronavirus disease 2019 (COVID-19) induced pneumonia.

Methods
We recorded the recovery status of 67 inpatients with hypertension and COVID-19 induced pneumonia in the Raytheon Mountain Hospital in Wuhan during February 12, 2020 and March 30, 2020. Patients treated with ACEI or ARBs were categorized in group A (n = 22), while patients who were not administered either ACEI or ARBs were categorized into group B (n = 45). We did a comparative analysis of various parameters such as the pneumonia progression, length-of-stay in the hospital, and the level of alanine aminotransferase (ALT), serum creatinine (Cr), and creatine kinase (CK) between the day when these patients were admitted to the hospital and the day when the treatment ended.

Results
These 67 hypertension cases counted for 33.17% of the total COVID-19 patients. There was no significant difference in the usage of drug treatment of COVID-19 between groups A and B (p > 0.05). During the treatment, 1 case in group A and 3 cases in group B progressed from mild pneumonia into severe pneumonia. Eventually, all patients were cured and discharged after treatment, and no recurrence of COVID-2019 induced pneumonia occurred after the discharge. The length of stays was shorter in group A as compared with group B, but there was no significant difference (p > 0.05). There was also no significant difference in other general parameters between the patients of the groups A and B on the day of admission to the hospital (p > 0.05). The ALT, CK, and Cr levels did not significantly differ between groups A and B on the day of admission and the day of discharge (p > 0.05).

Conclusions
To treat the hypertension patients with COVID-19 caused pneumonia, anti-hypertensive drugs (ACEs and ARBs) may be used according to the relative guidelines. The treatment regimen with these drugs does not need to be altered for the COVID-19 patients.
Persian version of the Barkin Index of Maternal Functioning (BIMF): a cross-cultural adaptation and psychometric evaluation
Authors: Ansariniaki Mehri , Lamyian Minoor , Ahmadi Fazlollah , Rahimi Foroushani Abbas , Curry Carolann L. , Barkin Jennifer L. 
Published: January 2021

Abstract
Background
Postpartum maternal functioning has the potential to affect the quality of interaction between mother and child. A proper assessment of maternal functioning requires a comprehensive and accurate tool. The objective of this study was to prepare a Persian version of the Barkin Index of Maternal Functioning (BIMF) and evaluate its psychometric properties in order to determine its applicability in Iranian mothers.

Methods
The BIMF was translated into Persian and then culturally adapted for Iranian women. After evaluating face and content validity, to perform factor analysis, a cross-sectional study was conducted using the Persian version of BIMF. The data was collected from two unique groups of 250 mothers (in all 500 mothers) who had infants 2 to 12-months old and who were selected using a two-stage cluster sampling method. Factor analysis, Pearson’s correlation, intra-class correlation coefficients (ICC), composite reliability (CR) and Cronbach’s alpha were employed in order to evaluate structural validity and reliability.

Results
Exploratory factor analysis resulted in a five-factor structure consisting of 20 items. Subsequently, confirmatory factor analysis (X 2/ df = 1.61, RMSEA = 0.050, GFI = 0.91, CFI = 0.91) confirmed that the Persian version had satisfactory goodness of fit. Reliability and internal consistency were confirmed with a CR of 0.77, an ICC of 0.87 and a Cronbach’s alpha of 0.81.

Conclusions
The findings indicated that the Persian version of the BIMF is a valid and reliable instrument for assessing maternal functioning among Iranian mothers.
“Like filling a lottery ticket with quite high stakes”: a qualitative study exploring mothers’ needs and perceptions of state-provided financial support for a child with a long-term illness in Finland
Authors: Paajanen Anna , Annerstedt Kristi Sidney , Atkins Salla 
Published: January 2021

Abstract
Background
A child’s long-term illness or disability is always a serious matter that impacts the whole family. Costs related to an illness can substantially affect a family’s financial situation. To date, there is little research on how parents experience available support for financial assistance. Surveys in Finland have found that families of children with long-term illnesses and disabilities could experience financial struggle and perceive the state provided financial support system as too complex. This article aimed to explore how caregivers of children with long-term illnesses perceived their financial situation, need for financial support and experienced its provision by the state in the Helsinki greater region.

Methods
Convenience sampling was used. Participants were contacted through peer-support groups on Facebook. Eleven mothers of children with varying long-term illnesses and disabilities residing in the Helsinki greater region were interviewed using in-depth interviews. Recordings of the interviews were transcribed and analysed using framework analysis. An analytical framework was built to label the dataset, which was then charted. Lastly, themes were formed through descriptive analysis.

Results
The main findings showed how the burden of caring for a child with a long-term illness or disability causes fatigue, which affects a family’s financial situation holistically. This affected both employment and financial management, but also receiving information about and applying for the state provided allowances. Mental resources were further depleted by seeking information and applying for allowances. This contributed to a vicious cycle between parental fatigue and financial struggle. Participants found the allocation of funds inequitable across the country. Finally, participants thought the allowance was insufficient in compensating for time spent caring for their child’s illness and did not consider their mental strain.

Conclusions
Even in a welfare state such as Finland, caregivers of children with long-term illnesses are at risk of poverty and struggle with the organization of state provided financial support. Policies should be designed to ensure equity across the country and consider how the parental fatigue should be addressed. The study has implications for achieving sustainable development goals on wellbeing and reducing poverty.