bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of pilot and small trials in meta-analyses of behavioral interventions: a meta-epidemiological study
Authors: Beets Michael W. , Weaver R. Glenn , Ioannidis John P. A. , Pfledderer Christopher D. , Jones Alexis , von Klinggraeff Lauren , Armstrong Bridget 
Published: February 2023

Abstracts
Background
Pilot/feasibility or studies with small sample sizes may be associated with inflated effects. This study explores the vibration of effect sizes (VoE) in meta-analyses when considering different inclusion criteria based upon sample size or pilot/feasibility status.

Methods
Searches were to identify systematic reviews that conducted meta-analyses of behavioral interventions on topics related to the prevention/treatment of childhood obesity from January 2016 to October 2019. The computed summary effect sizes (ES) were extracted from each meta-analysis. Individual studies included in the meta-analyses were classified into one of the following four categories: self-identified pilot/feasibility studies or based upon sample size but not a pilot/feasibility study (N ≤ 100, N > 100, and N > 370 the upper 75th of sample size). The VoE was defined as the absolute difference (ABS) between the re-estimations of summary ES restricted to study classifications compared to the originally reported summary ES. Concordance (kappa) of statistical significance of summary ES between the four categories of studies was assessed. Fixed and random effects models and meta-regressions were estimated. Three case studies are presented to illustrate the impact of including pilot/feasibility and N ≤ 100 studies on the estimated summary ES.

Results
A total of 1602 effect sizes, representing 145 reported summary ES, were extracted from 48 meta-analyses containing 603 unique studies (avg. 22 studies per meta-analysis, range 2–108) and included 227,217 participants. Pilot/feasibility and N ≤ 100 studies comprised 22% (0–58%) and 21% (0–83%) of studies included in the meta-analyses. Meta-regression indicated the ABS between the re-estimated and original summary ES where summary ES ranged from 0.20 to 0.46 depending on the proportion of studies comprising the original ES were either mostly small (e.g., N ≤ 100) or mostly large (N > 370). Concordance was low when removing both pilot/feasibility and N ≤ 100 studies (kappa = 0.53) and restricting analyses only to the largest studies (N > 370, kappa = 0.35), with 20% and 26% of the originally reported statistically significant ES rendered non-significant. Reanalysis of the three case study meta-analyses resulted in the re-estimated ES rendered either non-significant or half of the originally reported ES.

Conclusions
When meta-analyses of behavioral interventions include a substantial proportion of both pilot/feasibility and N ≤ 100 studies, summary ES can be affected markedly and should be interpreted with caution.
Aptamer-based CRISPR-Cas powered diagnostics of diverse biomarkers and small molecule targets
Authors: Kadam Ulhas Sopanrao , Cho Yuhan , Park Tae Yoon , Hong Jong Chan 
Published: February 2023

AbstractCRISPR-Cas systems have been widely used in genome editing and transcriptional regulation. Recently, CRISPR-Cas effectors are adopted for biosensor construction due to its adjustable properties, such as simplicity of design, easy operation, collateral cleavage activity, and high biocompatibility. Aptamers’ excellent sensitivity, specificity, in vitro synthesis, base-pairing, labeling, modification, and programmability has made them an attractive molecular recognition element for inclusion in CRISPR-Cas systems. Here, we review current advances in aptamer-based CRISPR-Cas sensors. We briefly discuss aptamers and the knowledge of Cas effector proteins, crRNA, reporter probes, analytes, and applications of target-specific aptamers. Next, we provide fabrication strategies, molecular binding, and detection using fluorescence, electrochemical, colorimetric, nanomaterials, Rayleigh, and Raman scattering. The application of CRISPR-Cas systems in aptamer-based sensing of a wide range of biomarkers (disease and pathogens) and toxic contaminants is growing. This review provides an update and offers novel insights into developing CRISPR-Cas-based sensors using ssDNA aptamers with high efficiency and specificity for point-of-care setting diagnostics.
Clinical efficacy and complications of transurethral resection of the prostate versus plasmakinetic enucleation of the prostate
Authors: Yang Chong-Yi , Chen Ge-Ming , Wu Yue-Xiang , Zhang Wei-Jie , Wang Jie , Chen Peng-Peng , Lou Zhen-Yuan 
Published: February 2023

Abstract
Background
Benign prostatic hyperplasia (BPH) is a common disease in elderly males, and many kinds of minimally invasive procedures can be used for the treatment of BPH. However, various procedures have caused some controversies regarding clinical outcomes, so more studies are needed to validate these controversial topics.

Aims
This study aimed to explore differences of clinical efficacy, surgical features, and complications between transurethral resection of the prostate (TURP) and plasmakinetic enucleation of the prostate (PKEP) for BPH.

Methods
A total of eligible 850 cases of BPH underwent TURP (the TURP group, 320 cases) or PKEP (the PKEP group, 530 cases) in the urology department of our hospital from March 2015 to 2018 were involved in this study. Then, the baseline data, surgical characteristics, IPSS, QoL, PVR, Qmax, IIEF-5, and documented complications were compared between the two groups.

Results
The operative time, intraoperative irrigation volume, postoperative hemoglobin, decrease in hemoglobin, postoperative irrigation time and volume, catheterization time, and hospital stay of the PKEP group were significantly less than those of the TURP group (all P < 0.05). At 3 months, 1, 2, and 3 years after operation, no significant differences were observed in IPSS, QoL, PVR, but the results of Qmax and IIEF-5 in the PKEP group were significantly higher than those parameters in the TURP group (all P < 0.05). The incidences of massive blood loss, postoperative secondary bleeding, blood transfusion, capsular perforation, urinary tract irritation, bladder spasm, clot retention, urinary tract infection, transient incontinence, erectile dysfunction, and the incidences of II, III grade of Clavien–Dindo classification in the PKEP group were significantly lower than those of the TURP group (all P < 0.05).

Conclusion
The clinical efficacy of PKEP is compared favorably with TURP during midterm follow-up. Given the merits such as less blood loss and hospital stay, lower complications, PKEP should be given a priority for BPH.
The essential roles of FXR in diet and age influenced metabolic changes and liver disease development: a multi-omics study
Authors: Yang Guiyan , Jena Prasant K. , Hu Ying , Sheng Lili , Chen Shin-Yu , Slupsky Carolyn M. , Davis Ryan , Tepper Clifford G. , Wan Yu-Jui Yvonne 
Published: February 2023

Abstract
Background
Aging and diet are risks for metabolic diseases. Bile acid receptor farnesoid X receptor (FXR) knockout (KO) mice develop metabolic liver diseases that progress into cancer as they age, which is accelerated by Western diet (WD) intake. The current study uncovers the molecular signatures for diet and age-linked metabolic liver disease development in an FXR-dependent manner.

Methods
Wild-type (WT) and FXR KO male mice, either on a healthy control diet (CD) or a WD, were euthanized at the ages of 5, 10, or 15 months. Hepatic transcriptomics, liver, serum, and urine metabolomics as well as microbiota were profiled.

Results
WD intake facilitated hepatic aging in WT mice. In an FXR-dependent manner, increased inflammation and reduced oxidative phosphorylation were the primary pathways affected by WD and aging. FXR has a role in modulating inflammation and B cell-mediated humoral immunity which was enhanced by aging. Moreover, FXR dictated neuron differentiation, muscle contraction, and cytoskeleton organization in addition to metabolism. There were 654 transcripts commonly altered by diets, ages, and FXR KO, and 76 of them were differentially expressed in human hepatocellular carcinoma (HCC) and healthy livers. Urine metabolites differentiated dietary effects in both genotypes, and serum metabolites clearly separated ages irrespective of diets. Aging and FXR KO commonly affected amino acid metabolism and TCA cycle. Moreover, FXR is essential for colonization of age-related gut microbes. Integrated analyses uncovered metabolites and bacteria linked with hepatic transcripts affected by WD intake, aging, and FXR KO as well as related to HCC patient survival.

Conclusion
FXR is a target to prevent diet or age-associated metabolic disease. The uncovered metabolites and microbes can be diagnostic markers for metabolic disease.
Optimal clinical protocols for total-body 18F-FDG PET/CT examination under different activity administration plans
Authors: Huang Yanchao , Wang Meng , Jiang Li , Wang Lijuan , Chen Li , Wang Qiaoyu , Feng Jiatai , Wang Jingyi , Xu Wanbang , Wu Hubing , Han Yanjiang 
Published: February 2023

Abstract
Background
Highly sensitive digital total-body PET/CT scanners (uEXPLORER) have great potential for clinical applications and fundamental research. Given their increasing sensitivity, low-dose scanning or snapshot imaging is now possible in clinics. However, a standardized total-body 18F-FDG PET/CT protocol is still lacking. Establishing a standard clinical protocol for total-body 18F-FDG PET/CT examination under different activity administration plans can help provide a theoretical reference for nuclear radiologists.

Methods
The NEMA image quality (IQ) phantom was used to evaluate the biases of various total-body 18F-FDG PET/CT protocols related to the administered activity, scan duration, and iterations. Several objective metrics, including contrast recovery (CR), background variability (BV), and contrast-to-noise ratio (CNR), were measured from different protocols. In line with the European Association of Nuclear Medicine Research Ltd. (EARL) guidelines, optimized protocols were suggested and evaluated for total-body 18F-FDG PET/CT imaging for three different injected activities.

Results
Our NEMA IQ phantom evaluation resulted in total-body PET/CT images with excellent contrast and low noise, suggesting great potential for reducing administered activity or shortening the scan duration. Different to the iteration number, prolonging the scan duration was the first choice for achieving higher image quality regardless of the activity administered. In light of image quality, tolerance of oncological patients, and the risk of ionizing radiation damage, the 3-min acquisition and 2-iteration (CNR = 7.54), 10-min acquisition and 3-iteration (CNR = 7.01), and 10-min acquisition and 2-iteration (CNR = 5.49) protocols were recommended for full-dose (3.70 MBq/kg), half-dose (1.95 MBq/kg), and quarter-dose (0.98 MBq/kg) activity injection schemes, respectively. Those protocols were applied in clinical practices, and no significant differences were observed for the SUVmax of large/small lesions or the SUVmean of different healthy organs/tissues.

Conclusion
These findings support that digital total-body PET/CT scanners can generate PET images with a high CNR and low-noise background, even with a short acquisition time and low administered activity. The proposed protocols for different administered activities were determined to be valid for clinical examination and can maximize the value of this imaging type.
Building Emotional Awareness and Mental Health (BEAM): an open-pilot and feasibility study of a digital mental health and parenting intervention for mothers of infants
Authors: Xie E. Bailin , Freeman Makayla , Penner-Goeke Lara , Reynolds Kristin , Lebel Catherine , Giesbrecht Gerald F. , Rioux Charlie , MacKinnon Anna , Sauer-Zavala Shannon , Roos Leslie E. , Tomfohr-Madsen Lianne 
Published: February 2023

AbstractBackgroundMaternal mental health concerns and parenting stress in the first few years following childbirth are common and pose significant risks to maternal and child well-being. The COVID-19 pandemic has led to increases in maternal depression and anxiety and has presented unique parenting stressors. Although early intervention is crucial, there are significant barriers to accessing care.MethodsTo inform a larger randomized controlled trial, the current open-pilot trial investigated initial evidence for the feasibility, acceptability, and efficacy of a newly developed online group therapy and app-based mental health and parenting program (BEAM) for mothers of infants. Forty-six mothers 18 years or older with clinically elevated depression scores, with an infant aged 6–17 months old, and who lived in Manitoba or Alberta were enrolled in the 10-week program (starting in July 2021) and completed self-report surveys.ResultsThe majority of participants engaged in each of the program components at least once and participants indicated relatively high levels of app satisfaction, ease of use, and usefulness. However, there was a high level of attrition (46%). Paired-samplet-tests indicated significant pre- to post-intervention change in maternal depression, anxiety, and parenting stress, and in child internalizing, but not externalizing symptoms. Effect sizes were in the medium to high range, with the largest effect size observed for depressive symptoms (Cohen’sd= .93).DiscussionThis study shows moderate levels of feasibility and strong preliminary efficacy of the BEAM program. Limitations to program design and delivery are being addressed for testing in adequately powered follow-up trials of the BEAM program for mothers of infants.Trial registrationNCT04772677. Registered on February 26 2021.
Identification of cell-biologic mechanisms of coronary artery spasm and its ex vivo diagnosis using peripheral blood-derived iPSCs
Authors: Yang Han-Mo , Lee Joo-Eun , Kim Ju-Young , You Jihye , Kim Joonoh , Lee Hak Seung , Yoo Hee Min , Kong Min Gyu , Han Jung-Kyu , Cho Hyun-Jai , Park Kyung Woo , Kang Hyun-Jae , Koo Bon-Kwon , Park Young-Bae , Kim Hyo-Soo 
Published: February 2023

Abstract

Background
Although vasospastic angina (VSA) is known to be caused by coronary artery spasm, no study has fully elucidated the exact underlying mechanism. Moreover, in order to confirm VSA, patients should undergo invasive coronary angiography with spasm provocation test. Herein, we investigated the pathophysiology of VSA using peripheral blood-derived induced pluripotent stem cells (iPSCs) and developed an ex vivo diagnostic method for VSA.

Methods and results

With 10 mL of peripheral blood from patients with VSA, we generated iPSCs and differentiated these iPSCs into target cells. As compared with vascular smooth muscle cells (VSMCs) differentiated from iPSCs of normal subjects with negative provocation test, VSA patient-specific iPSCs-derived VSMCs showed very strong contraction in response to stimulants. Moreover, VSA patient-specific VSMCs exhibited a significant increase in stimulation-induced intracellular calcium efflux (Changes in the relative fluorescence unit [ΔF/F]; Control group vs. VSA group, 2.89 ± 0.34 vs. 10.32 ± 0.51,
p
< 0.01), and exclusively induced a secondary or tertiary peak of calcium efflux, suggesting that those findings could be diagnostic cut-off values for VSA. The observed hyperreactivity of VSA patient-specific VSMCs were caused by the upregulation of sarco/endoplasmic reticulum Ca
2+
-ATPase 2a (SERCA2a) due to its enhanced small ubiquitin-related modifier
(
SUMO)ylation. This increased activity of SERCA2a was reversed by treatment with ginkgolic acid, an inhibitor of SUMOylated E1 molecules (pi/µg protein; VSA group vs. VSA + ginkgolic acid, 52.36 ± 0.71 vs. 31.93 ± 1.13,
p
< 0.01).

Conclusions
Our findings showed that abnormal calcium handling in sarco/endoplasmic reticulum could be induced by the enhanced SERCA2a activity in patients with VSA, leading to spasm. Such novel mechanisms of coronary artery spasm could be useful for drug development and diagnosis of VSA.
Research Buddy partnership in a MD–PhD program: lessons learned
Authors: Gould Daniel J. , Glanville-Hearst Marion , Bunzli Samantha , Choong Peter F. M. , Dowsey Michelle M. 
Published: February 2023

AbstractBackground and aimsThere is increasing recognition of the importance of patient involvement in research. In recent years, there has also been growing interest in patient partnerships with doctoral studies students. However, it can be difficult to know where to start and how to go about such involvement activities. The purpose of this perspective piece was to share experiential insight of the experience of a patient involvement program such that others can learn from this experience.BodyThis is a co-authored perspective piece centred on the experience of MGH, a patient who has had hip replacement surgery, and DG, a medical student completing a PhD, participating in a Research Buddy partnership over the course of over 3 years. The context in which this partnership took place was also described to facilitate comparison with readers’ own circumstances and contexts. DG and MGH met regularly to discuss, and work together on, various aspects of DG’s PhD research project. Reflexive thematic analysis was conducted on reflections from DG and MGH regarding their experience in the Research Buddy program to synthesise nine lessons which were then corroborated with reference to published literature on patient involvement in research. These lessons were: learn from experience; tailor the program; get involved early; embrace uniqueness; meet regularly; build rapport; ensure mutual benefit; broad involvement; regularly reflect and review.ConclusionsIn this perspective piece, a patient and a medical student completing a PhD reflected upon their experience co-designing a Research Buddy partnership within a patient involvement program. A series of nine lessons was identified and presented to inform readers seeking to develop or enhance their own patient involvement programs. Researcher-patient rapport is foundational to all other aspects of the patient’s involvement.
Efficacy and safety of cardioprotective drugs in chemotherapy-induced cardiotoxicity: an updated systematic review & network meta-analysis
Authors: Mir Ali , Badi Yasra , Bugazia Seif , Nourelden Anas Zakarya , Fathallah Ahmed Hashem , Ragab Khaled Mohamed , Alsillak Mohammed , Elsayed Sarah Makram , Hagrass Abdulrahman Ibrahim , Bawek Sawyer , Kalot Mohamad , Brumberger Zachary L. 
Published: February 2023

Abstract
Background
Cancer patients receiving chemotherapy have an increased risk of cardiovascular complications. This limits the widespread use of lifesaving therapies, often necessitating alternate lower efficacy regimens, or precluding chemotherapy entirely. Prior studies have suggested that using common cardioprotective agents may attenuate chemotherapy-induced cardiotoxicity. However, small sample sizes and conflicting outcomes have limited the clinical significance of these results.

Hypothesis
A comprehensive network meta-analysis using updated and high-quality data can provide more conclusive information to assess which drug or drug class has the most significant effect in the management of chemotherapy-induced cardiotoxicity.

Methods
We performed a literature search for randomized controlled trials (RCTs) investigating the effects of cardioprotective agents in patients with chemotherapy-induced cardiotoxicity. We used established analytical tools (netmeta package in RStudio) and data extraction formats to analyze the outcome data. To obviate systematic bias in the selection and interpretation of RCTs, we employed the validated Cochrane risk-of-bias tools. Agents included were statins, aldosterone receptor antagonists (MRAs), ACEIs, ARBs, and beta-blockers. Outcomes examined were improvement in clinical and laboratory parameters of cardiac function including a decreased reduction in left ventricular ejection fraction (LVEF), clinical HF, troponin-I, and B-natriuretic peptide levels.

Results
Our study included 33 RCTs including a total of 3,285 patients. Compared to control groups, spironolactone therapy was associated with the greatest LVEF improvement (Mean difference (MD) = 12.80, [7.90; 17.70]), followed by enalapril (MD = 7.62, [5.31; 9.94]), nebivolol (MD = 7.30, [2.39; 12.21]), and statins (MD = 6.72, [3.58; 9.85]). Spironolactone was also associated with a significant reduction in troponin elevation (MD =  − 0.01, [− 0.02; − 0.01]). Enalapril demonstrated the greatest BNP reduction (MD =  − 49.00, [− 68.89; − 29.11]), which was followed by spironolactone (MD =  − 16.00, [− 23.9; − 8.10]). Additionally, patients on enalapril had the lowest risk of developing clinical HF compared to the control population (RR = 0.05, [0.00; 0.75]).

Conclusion
Our analysis reaffirmed that statins, MRAs, ACEIs, and beta-blockers can significantly attenuate chemotherapy-induced cardiotoxicity, while ARBs showed no significant effects. Spironolactone showed the most robust improvement of LVEF, which best supports its use among this population. Our analysis warrants future clinical studies examining the cardioprotective effects of cardiac remodeling therapy in cancer patients treated with chemotherapeutic agents.
Serum Calcium Concentrations and Risk of All-Cause and Cause-Specific Mortality: Results From 2 Prospective Cohorts
Authors: Yang Mingjia , Miao Junyan , Du Lingbin , Wang Jiayu , Yang Jing , Lu Jiayi , Fan Xikang , Huang Changzhi , Fu Zan , Xu Zekuan , Song Mingyang , Ma Hongxia , Jin Guangfu , Hu Zhibin , Hang Dong , Shen Hongbing 
Published: February 2023

Abstract

Context
Calcium plays a critical role in various physiological activities. However, the association between circulating calcium concentrations and mortality in a general healthy population remains undetermined.

Objective
To examine the association of serum calcium concentrations with all-cause and cause-specific mortality.

Methods
Leveraging data from the UK Biobank (n = 361 662) and the US National Health and Nutrition Examination Survey (NHANES, n = 36 985), we prospectively examined the association of serum calcium concentrations with all-cause and cause-specific mortality using Cox proportional hazard and restricted cubic spline models.

Results
During a median follow-up of 12.0 years, UK Biobank documented 18 327 deaths, including 3119 (17.0%) from cardiovascular disease (CVD) and 9599 (52.4%) from cancer. We found a U-shaped relationship of albumin-adjusted calcium concentrations with all-cause and CVD mortality. Compared with participants with moderate calcium levels (the third quintile, Q3), those with low and high levels had an increased risk of all-cause (hazard ratio [HR] 1.02 for Q1 vs Q3; 1.10 for Q5 vs Q3) and CVD mortality (HR 1.11 for Q1 vs Q3; 1.25 for Q5 vs Q3). In contrast, there was a linear positive relationship with cancer mortality (HR 1.09 for Q5 vs Q1). Similar results for all-cause, CVD, and cancer mortality were observed in US NHANES.

Conclusion
Our findings provide novel insights into the association between serum calcium concentrations and mortality in the general healthy population.