bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Guide to Estimating the Reference Range From a Meta-Analysis Using Aggregate or Individual Participant Data
Authors: Siegel Lianne , Murad M Hassan , Riley Richard D , Bazerbachi Fateh , Wang Zhen , Chu Haitao 
Published: January 2022

AbstractClinicians frequently must decide whether a patient’s measurement reflects that of a healthy “normal” individual. Thus, the reference range is defined as the interval in which some proportion (frequently 95%) of measurements from a healthy population is expected to fall. One can estimate it from a single study or preferably from a meta-analysis of multiple studies to increase generalizability. This range differs from the confidence interval for the pooled mean and the prediction interval for a new study mean in a meta-analysis, which do not capture natural variation across healthy individuals. Methods for estimating the reference range from a meta-analysis of aggregate data that incorporates both within- and between-study variations were recently proposed. In this guide, we present 3 approaches for estimating the reference range: one frequentist, one Bayesian, and one empirical. Each method can be applied to either aggregate or individual-participant data meta-analysis, with the latter being the gold standard when available. We illustrate the application of these approaches to data from a previously published individual-participant data meta-analysis of studies measuring liver stiffness by transient elastography in healthy individuals between 2006 and 2016.
Four-Day Food Record Macronutrient Intake, With and Without Biomarker Calibration, and Chronic Disease Risk in Postmenopausal Women
Authors: Prentice Ross L , Pettinger Mary , Neuhouser Marian L , Raftery Daniel , Zheng Cheng , Gowda G A Nagana , Huang Ying , Tinker Lesley F , Howard Barbara V , Manson JoAnn E , Wallace Robert , Mossavar-Rahmani Yasmin , Johnson Karen C , Lampe Johanna W 
Published: January 2022

AbstractWe recently evaluated associations of biomarker-calibrated protein intake, protein density, carbohydrate intake, and carbohydrate density with the incidence of cardiovascular disease, cancer, and diabetes among postmenopausal women in the Women’s Health Initiative (1993–present, 40 US clinical centers). The biomarkers relied on serum and urine metabolomics profiles, and biomarker calibration used regression of biomarkers on food frequency questionnaires. Here we develop corresponding calibration equations using food records and dietary recalls. In addition, we use calibrated intakes based on food records in disease association estimation in a cohort subset (n = 29,294) having food records. In this analysis, more biomarker variation was explained by food records than by FFQs for absolute macronutrient intake, with 24-hour recalls being intermediate. However, the percentage of biomarker variation explained was similar for each assessment approach for macronutrient densities. Invasive breast cancer risk was related inversely to carbohydrate and protein densities using food records, in analyses that included (calibrated) total energy intake and body mass index. Corresponding analyses for absolute intakes did not differ from the null, nor did absolute or relative intakes associate significantly with colorectal cancer or coronary heart disease. These analyses do not suggest major advantages for food records or dietary recalls in comparison with less costly and logistically simpler food frequency questionnaires for these nutritional variables.
Blood Pressure Control Among Non-Hispanic Black Adults Is Lower Than Non-Hispanic White Adults Despite Similar Treatment With Antihypertensive Medication: NHANES 2013–2018
Authors: Hayes Donald K , Jackson Sandra L , Li Yanfeng , Wozniak Gregory , Tsipas Stavros , Hong Yuling , Thompson-Paul Angela M , Wall Hilary K , Gillespie Cathleen , Egan Brent M , Ritchey Matthew D , Loustalot Fleetwood 
Published: January 2022

Abstract

BACKGROUND
Controlled blood pressure can prevent or reduce adverse health outcomes. Social and structural determinants may contribute to the disparity that despite equivalent proportions on antihypertensive medication, non-Hispanic Black (Black) adults have lower blood pressure control and more cardiovascular events than non-Hispanic White (White) adults.

METHODS
Data from 2013 to 2018 National Health and Nutrition Examination Survey were pooled to assess control among Black and White adults by antihypertensive medication use and selected characteristics using the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Blood Pressure Guideline definition (systolic blood pressure &lt;130 mm Hg and diastolic blood pressure &lt;80 mm Hg) among 4,739 adults.

RESULTS
Among those treated with antihypertensive medication, an estimated 34.9% of Black and 45.0% of White adults had controlled blood pressure. Control was lower for Black and White adults among most subgroups of age, sex, education, insurance status, usual source of care, and poverty–income ratio. Black adults had higher use of diuretics (28.5%—Black adults vs. 23.5%—White adults) and calcium channel blockers (24.2%—Black adults vs. 14.7%—White adults) compared with White adults. Control among Black adults was lower than White adults across all medication classes including diuretics (36.1%—Black adults vs. 47.3%—White adults), calcium channel blockers (30.2%—Black adults vs. 40.1%—White adults), and number of medication classes used.

CONCLUSIONS
Suboptimal blood pressure control rates and disparities warrant increased efforts to improve control, which could include addressing social and structural determinants along with emphasizing implementation of the 2017 ACC/AHA Blood Pressure Guideline into clinical practice.
Implementation of a pharmacy-led virtual academic detailing program at the US Veterans Health Administration
Authors: Himstreet Julianne E , Shayegani Ramona , Spoutz Patrick , Hoffman Jonathan D , Midboe Amanda M , Hillman Ashley , Marin Jennifer , Chen Andrea , Smith Jason P , Manning Jane M , Almeida Andrea , Gray Caroline P , Erhardt Taryn A , Garcia Carla C , Freeman Blake A , Christopher Melissa L D , Bounthavong Mark 
Published: January 2022

Abstract

Purpose
To provide a summary of the implementation of a virtual academic detailing pilot program at the US Department of Veterans Affairs (VA).

Summary
In September 2018, VA Pharmacy Benefits Management implemented a virtual academic detailing (“e-Detailing”) pilot program across 3 regional networks. Academic detailing involves multifaceted collaborative outreach delivered by trained healthcare clinicians to other clinicians using targeted educational interventions that improve clinical decision-making. Across VA, academic detailing programs are primarily staffed by specially trained clinical pharmacist specialists. Implementation began with an in-person meeting to train academic detailers on using the virtual academic detailing platform (VA Video Connect) and virtual soft skills, which was followed by regular facilitation meetings to address issues and share experiences. During e-Detailing program implementation, coronavirus disease 2019 (COVID-19) emerged, prompting the US Department of Health and Human Services to declare a public health emergency. VA followed with restrictions on nonessential travel for all employees, thus hampering in-person academic detailing activities. Fortunately, e-Detailing provided an alternative channel for academic detailers across VA to continue delivering critical outreach to providers during the pandemic. Qualitative assessment of academic detailers’ and providers’ perceptions on e-Detailing highlighted the need for local leadership support for e-Detailing and telehealth, the efficiency of virtual compared to in-person visits, and potential time savings resulting from avoidance of long commutes.

Conclusion
The timing of e-Detailing implementation during the COVID-19 pandemic illustrates the need and potential for a virtual platform to deliver timely provider outreach.
Feeding level is associated with altered liver transcriptome and follicle selection in hen
Authors: Stephens Claire S , Hill-Ricciuti Alexandra , Francoeur Laurie , Johnson Patricia A 
Published: January 2022

Abstract
Genetic selection for particular traits in domestic animals may have altered the optimal feedback regulation among systems regulating appetite, growth, and reproduction. Broiler breeder chickens have been selected for fast and efficient growth and, unless feed restricted, consume excessively resulting in poor reproductive efficiency. We examined the effect of dietary treatment in full-fed and restricted-fed broiler breeder hens on ovarian responses, liver morphology, and transcriptome associated with reproductive function. Although full-fed broiler breeder hens had lower egg production (P &lt; 0.01), the total number of ovarian follicles &gt;8 mm (P &lt; 0.01), 6–8 mm (P &lt; 0.03), and 3–5 mm (P &lt; 0.04) were greater in full-fed hens compared to restricted-fed hens. There was a large amount of lipid accumulation in the liver of full-fed hens and differential gene analysis yielded 120 genes that were differentially expressed &gt;2-fold in response to feeding level (P &lt; 0.01; false discovery rate &lt; 0.05). Elevated T3 may indicate that general metabolism was affected by diet and GHR (P &lt; 0.01) and insulin like growth factor 1 (IGF1) (P &lt; 0.04) mRNA expression were both greater in the liver of full-fed hens as compared to restricted-fed hens. It is likely that selection for increased growth, associated with enhanced activity of the IGF1 system, has altered nutritional coupling of feed intake to follicle development.
Extended-course antibiotic prophylaxis in lower limb amputation: randomized clinical trial
Authors: Souroullas Panayiotis , Barnes Rachel , Carradice Daniel , Smith George , Huang Chao , Chetter Ian 
Published: January 2022

Abstract

Background
Lower limb amputation (LLA) is typically described as ‘clean surgery’, but surgical-site infection (SSI) rates are high and there is significant variation in antibiotic prophylaxis practice. This study aimed to determine whether an extended period of antibiotic prophylaxis (5-day course) is superior to a short course (24 h) in preventing SSI in patients undergoing minor and major LLA.

Methods
Patients undergoing minor and major amputation from a single vascular unit were recruited and randomized to receive either a 5-day or a 24-h prophylactic course of antibiotics. Patients with significant baseline infection were excluded. Outcomes included the incidence of SSI and impaired wound healing (IWH), both measured using ASEPSIS criteria, the need for further surgery, duration of hospital stay, and mortality up to 1 year.

Results
Some 161 patients were recruited to the study, and 152 were included in the analysis. A 5-day course of antibiotics was associated with a lower incidence of SSI (11.8 versus 39.5 per cent; P &lt; 0.001) and lower incidence of IWH (22.4 versus 58 per cent; P &lt; 0.001). Fewer patients receiving the 5-day course required amputation revisional surgery (6.6 versus 21 per cent; P = 0.010). Duration of hospital stay and mortality rates were similar. The presence of SSI (odds ratio (OR) 5.14, 95 per cent c.i. 1.96 to 13.45; P &lt; 0.001) and IWH (OR 4.62, 1.68 to 12.72; P = 0.003) increased the need for revisional surgery. SSI increased the duration of hospital stay: median 28 (i.q.r. 16–40) versus 14 (9–21) days (P = 0.045).

Conclusion
SSI and IWH are common after LLA and have a significant impact on outcome. A 5-day course of antibiotic prophylaxis was associated with a reduction in both SSI and IWH compared with a 24-h course, and this reduced the need for further surgery. Registration number: NCT02018094 (http://www.clinicaltrials.gov); EudraCT 2012-003146-32 (https://www.clinicaltrialsregister.eu).
Betulinic acid accelerates diabetic wound healing by modulating hyperglycemia-induced oxidative stress, inflammation and glucose intolerance
Authors: Xie Weiguo , Hu Weigang , Huang Zhuo , Li Min , Zhang Hongyu , Huang Xiaodong , Yao Paul 
Published: January 2022

Abstract

Background
Diabetes significantly delays wound healing through oxidative stress, inflammation and impaired re-epithelialization that lead to defective regulation of the healing process, although the related mechanism remains unclear. Here, we aim to investigate the potential role and mechanism for the beneficial effect of betulinic acid (BA) on diabetic wound healing.

Methods
The molecular effect of BA on hyperglycemia-mediated gene expression, oxidative stress, inflammation and glucose uptake was evaluated in endothelial, fibroblast and muscle cells. Burn injury was introduced to streptozotocin-induced diabetic rats and BA administration through either an intraperitoneal (IP) or topical (TOP) technique was used for wound treatment. Glucose tolerance was evaluated in both muscle tissue and fibroblasts, while oxidative stress and inflammation were determined in both the circulatory system and in wound tissues. The effect of BA on the wound healing process was also evaluated.

Results
BA treatment reversed hyperglycemia-induced glucose transporter type 4 (GLUT4) suppression in both muscle and fibroblast cells. This treatment also partly reversed hyperglycemia-mediated suppression of endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and nuclear factor NFκB p65 subunit (NFκB p65) activation in endothelial cells. An in vivo rat study showed that BA administration ameliorated diabetes-mediated glucose intolerance and partly attenuated diabetes-mediated oxidative stress and inflammation in both the circulatory system and wound tissues. BA administration by both IP and TOP techniques significantly accelerated diabetic wound healing, while BA administration by either IP or TOP methods alone had a significantly lower effect.

Conclusions
BA treatment ameliorates hyperglycemia-mediated glucose intolerance, endothelial dysfunction, oxidative stress and inflammation. Administration of BA by both IP and TOP techniques was found to significantly accelerate diabetic wound healing, indicating that BA could be a potential therapeutic candidate for diabetic wound healing.
Kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222
Authors: Jayathilaka Deshni , Jeewandara Chandima , Gomes Laksiri , Jayadas Tibutius Thanesh Pramanayagam , Kamaladasa Achala , Somathilake Gayasha , Guruge Dinuka , Pushpakumara Pradeep Darshana , Ranasinghe Thushali , Aberathna Inoka Sepali , Danasekara Saubhagya , Gunathilaka Buddini , Kuruppu Heshan , Wijewickrama Ananda , Wijayamuni Ruwan , Schimanski Lisa , Tan T K , Ogg Graham S , Townsend Alain , Malavige Gathsaurie Neelika 
Published: January 2022

Abstract
To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222 (Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD, and N proteins in patients at 4 weeks and 12 weeks since the onset of illness or following vaccination. Antibodies to the receptor-binding domain of SARS-CoV-2 wild type (WT), α, β, and λ and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. For those with mild illness and in vaccines, the IgG responses to S1, S2, RBD, and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccines, IgG antibodies to the S2 subunit had the highest significant rise (P &lt; 0.0001). Vaccines had several-fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the haemagglutination test (HAT) titres were significantly lower to the α in vaccines and significantly lower in those with mild illness and in vaccines to β and for λ. No such difference was seen in those with moderate/severe illness. Vaccines had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccines had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs.
Effects of DRD2/ANKK1 and COMT Val158Met polymorphisms on stabilization against and adaptation to unexpected events
Authors: Trempler Ima , Binder Ellen , Reuter Martin , Plieger Thomas , Standke Isabel , Mecklenbrauck Falko , Meinert Susanne , Forstner Andreas J , Nöthen Markus M , Rietschel Marcella , Stürmer Sophie , Dannlowski Udo , Tittgemeyer Marc , Lencer Rebekka , Fink Gereon R , Schubotz Ricarda I 
Published: January 2022

Abstract
Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise. In contrast, there were overall smaller differences in behavioral and neural modulation by drift surprise. Our results suggest that the impact of dopamine-relevant polymorphisms in the flexibility-stability trade-off may result in part from the role of dopamine in encoding the weight afforded to events requiring updating or stabilization.
Corticocortical innervation subtypes of layer 5 intratelencephalic cells in the murine secondary motor cortex
Authors: Im Sanghun , Ueta Yoshifumi , Otsuka Takeshi , Morishima Mieko , Youssef Mohammed , Hirai Yasuharu , Kobayashi Kenta , Kaneko Ryosuke , Morita Kenji , Kawaguchi Yasuo 
Published: January 2022

Abstract
Feedback projections from the secondary motor cortex (M2) to the primary motor and sensory cortices are essential for behavior selection and sensory perception. Intratelencephalic (IT) cells in layer 5 (L5) contribute feedback projections to diverse cortical areas. Here we show that L5 IT cells participating in feedback connections to layer 1 (L1) exhibit distinct projection patterns, genetic profiles, and electrophysiological properties relative to other L5 IT cells. An analysis of the MouseLight database found that L5 IT cells preferentially targeting L1 project broadly to more cortical regions, including the perirhinal and auditory cortices, and innervate a larger volume of striatum than the other L5 IT cells. We found experimentally that in upper L5 (L5a), ER81 (ETV1) was found more often in L1-preferring IT cells, and in IT cells projecting to perirhinal/auditory regions than those projecting to primary motor or somatosensory regions. The perirhinal region-projecting L5a IT cells were synaptically connected to each other and displayed lower input resistance than contra-M2 projecting IT cells including L1-preferring and nonpreferring cells. Our findings suggest that M2-L5a IT L1-preferring cells exhibit stronger ER81 expression and broader cortical/striatal projection fields than do cells that do not preferentially target L1.
Clinical Decision Support Systems to Reduce Unnecessary Clostridioides difficile Testing Across Multiple Hospitals
Authors: Rock Clare , Abosi Oluchi , Bleasdale Susan , Colligan Erin , Diekema Daniel J , Dullabh Prashila , Gurses Ayse P , Heaney-Huls Krysta , Jacob Jesse T , Kandiah Sheetal , Lama Sonam , Leekha Surbhi , Mayer Jeanmarie , Mena Lora Alfredo J , Morgan Daniel J , Osei Patience , Pau Sara , Salinas Jorge L , Spivak Emily , Wenzler Eric , Cosgrove Sara E 
Published: January 2022

Abstract

Background
Inappropriate Clostridioides difficile testing has adverse consequences for patients, hospitals, and public health. Computerized clinical decision support (CCDS) systems in the electronic health record (EHR) may reduce C. difficile test ordering; however, effectiveness of different approaches, ease of use, and best fit into healthcare providers’ (HCP) workflow are not well understood.

Methods
Nine academic and 6 community hospitals in the United States participated in this 2-year cohort study. CCDS (hard stop or soft stop) triggered when a duplicate C. difficile test order was attempted or if laxatives were recently received. The primary outcome was the difference in testing rates pre– and post–CCDS interventions, using incidence rate ratios (IRRs) and mixed-effect Poisson regression models. We performed qualitative evaluation (contextual inquiry, interviews, focus groups) based on a human factors model. We identified themes using a codebook with primary nodes and subnodes.

Results
In 9 hospitals implementing hard-stop CCDS and 4 hospitals implementing soft-stop CCDS, C. difficile testing incidence rate (IR) reduction was 33% (95% confidence interval [CI]: 30%–36%) and 23% (95% CI: 21%–25%), respectively. Two hospitals implemented a non-EHR-based human intervention with IR reduction of 21% (95% CI: 15%–28%). HCPs reported generally favorable experiences and highlighted time efficiencies such as inclusion of the patient’s most recent laxative administration on the CCDS. Organizational factors, including hierarchical cultures and communication between HCPs caring for the same patient, impact CCDS acceptance and integration.

Conclusions
CCDS systems reduced unnecessary C. difficile testing and were perceived positively by HCPs when integrated into their workflow and when displaying relevant patient-specific information needed for decision making.