bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics analysis of DNA replication-associated primase polymerase (PRIMPOL) in pan-cancer: a potential target for prognosis and immune response
Authors: Deng Langmei , Thakur Abhimanyu , Peng Jinwu , Song Liying , Li Zhilan 
Published: June 2023

Abstract
Background
It is critical to understand the mechanisms of human cancers in order to develop the effective anti-cancer therapeutic strategies. Recent studies indicated that primase polymerase (PRIMPOL) is strongly associated with the development of human cancers. Nevertheless, a systematic pan-cancer analysis of PRIMPOL remains to be further clarified.

Method
Comprehensive multi-omics bioinformatics algorithms, such as TIMER2.0, GEPIA2.0 and cBioPortal, were utilized to evaluate the biological roles of PRIMPOL in pan-cancer, including the expression profiles, genomic alterations, prognostic values and immune regulation.

Results
PRIMPOL was upregulated in glioblastoma multiforme and kidney renal clear cell carcinoma. The brain lower grade glioma patients with enhanced PRIMPOL expression displayed poor prognostic values. We also demonstrated the PRIMPOL's immunomodulating effects on pan-cancer as well as its genomic changes and methylation levels. The aberrant expression of PRIMPOL was linked to various cancer-associated pathways, including DNA damage response, DNA repair, and angiogenesis, according to single-cell sequencing and function enrichment.

Conclusions
This pan-cancer analysis offers a thorough review of the functional roles of PRIMPOL in human cancers, suggesting PRIMPOL as a potentially important biomarker for the progression and immunotherapy of various cancers.
Benzylpenicillin concentrations in umbilical cord blood and plasma of premature neonates following intrapartum doses for group B streptococcal prophylaxis
Authors: Samb Amadou , Dierikx Thomas H. , Bijleveld Yuma A. , de Haan Timo R. , Hodiamont Caspar J. , van Leeuwen Elisabeth , van Kaam Anton H. L. C. , Mathôt Ron A. A. , Visser Douwe H. 
Published: June 2023

Abstract
Background and method
Dutch obstetrics guideline suggest an initial maternal benzylpenicillin dose of 2,000,000 IU followed by 1,000,000 IU every 4 h for group-B-streptococci (GBS) prophylaxis. The objective of this study was to evaluate whether concentrations of benzylpenicillin reached concentrations above the minimal inhibitory concentrations (MIC) in umbilical cord blood (UCB) and neonatal plasma following the Dutch guideline.

Results
Forty-six neonates were included. A total of 46 UCB samples and 18 neonatal plasma samples were available for analysis. Nineteen neonates had mothers that received intrapartum benzylpenicillin. Benzylpenicillin in UCB corresponded to concentrations in plasma drawn directly postpartum (R2 = 0.88, p < 0.01). A log-linear regression suggested that benzylpenicillin concentrations in neonates remained above the MIC threshold 0.125 mg/L up to 13.0 h after the last intrapartum dose.

Conclusions
Dutch intrapartum benzylpenicillin doses result in neonatal concentrations above the MIC of GBS.
The feasibility and acceptability of an app-based cognitive strategy training programme for older people
Authors: Tulliani Nikki , Bye Rosalind , Bissett Michelle , Coutts Samantha , Liu Karen P. Y. 
Published: June 2023

Abstract
Background
Increasing numbers of people are living with mild cognitive impairment in later life and seeking therapy to maintain cognition to remain as independent as possible in daily life. Based on a review of the literature, an app-based programme using perceptual-encoding strategies called Enhancing Memory in Daily Life (E-MinD Life) was developed. An expert panel reviewed the programme’s appropriateness for older people with and without mild cognitive impairment. As part of the design process, the feasibility and acceptability of the E-MinD Life programme were then assessed in relation to its use by healthy older adults, with findings informing the application of the programme to older people with mild cognitive impairment in the future.

Methods
Phase 1: The E-MinD Life programme was reviewed by an expert panel of occupational therapists. Experts rated the programme on a Likert scale and answered open-ended questions in relation to feasibility, clarity, and relevancy. Phase 2 involved field-testing the 9-week programme with a sample of nine healthy older people. Participants rated the acceptability of the programme on a Likert scale questionnaire. Data on recruitment rates and retention, and adherence and duration of sessions were collected to determine the feasibility of the programme. Responses to the Likert scale were analysed using descriptive statistics. Open-ended responses were categorised qualitatively using a constant comparative approach.

Results
Phase 1: Experts indicated that the E-MinD Life programme was feasible and included relevant activities for community living. Although experts felt that an older user with mild NCD would be able to independently complete the programme, the qualitative analysis suggests formatting changes in future iterations of the programme to enhance visual clarity. Phase 2: All participants completed the 9-week programme. The average number of self-administered sessions attempted over the 9-week period was 13.44 (SD = 6.73) out of 18 scheduled sessions. Overall, most participants found the programme relevant, logical and easy to understand, and perceived it to be effective for functional cognitive problems.

Conclusion
The E-MinD Life programme shows promise for inclusion into trial designs to determine the effectiveness of the cognitive strategy programme for older people with and without cognitive impairment.

Trial registration
ClinicalTrials.gov, NCT03430401. Registered 1 February 2018.
Effects of soil potassium levels on dry matter and nutrient accumulation and distribution in cotton
Authors: SHAO Jingjing , DONG Helin , JIN Yinan , LI Pengcheng , SUN Miao , FENG Weina , ZHENG Cangsong 
Published: June 2023

Abstract
Background
Potassium (K) is an essential nutrient for plant growth and development. However, plant fertilization ignoring the soil K level is very likely to cause excessive fertilizer use, and further arouse a series of side effects. This study investigated the response of cotton growth to different soil K levels and the uptake of major nutrients, aiming to evaluate the appropriate K supply level for cotton growth. Using a random block design with 6 soil K levels, we conducted 18 micro-zones field experiments over two continuous years. The soil available K concentration of each treatment was K1 (99.77–100.90 mg·kg−1), K2 (110.90–111.26 mg·kg−1), K3 (123.48–128.88 mg·kg−1), K4 (140.13–145.10 mg·kg−1), K5 (154.43–155.38 mg·kg−1), and K6 (165.77–168.75 mg·kg−1). Cotton nutrient contents, soil nutrient contents, accumulation and distribution of dry matter in cotton were determined, and the relationships between K content in soil and plants and dry matter accumulation were analyzed.

Results
The soil K content had a significantly positive relationship with dry matter and K accumulation in cotton plants. There were significant differences in dry matter accumulation, single-plant seed cotton yield, mineral nutrient uptake and the proportion of K accumulation in reproductive organs among different soil K levels. The results showed that there was significant difference between K4 and lower K level treatments (K1 and K2), but no significant difference between K4 and higher K level treatments (K5 and K6) in dry matter, single-plant seed cotton yield, or accumulation, distribution and seed cotton production efficiency of N, P and K.

Conclusion
The soil K level of K4 was able to provide sufficient K for cotton growth in our experiment. Therefore, when the soil K level reached 140.13 mg·kg−1, further increasing the soil K concentration no longer had a significant positive effect on cotton growth.
Resting heart rate and cardiovascular outcomes in patients with non-paroxysmal atrial fibrillation: CODE-AF registry
Authors: Park Hanjin , Yu Hee Tae , Kim Tae-Hoon , Park Junbeom , Park Jin-Kyu , Kang Ki-Woon , Shim Jaemin , Kim Jin-Bae , Kim Jun , Choi Eue-Keun , Park HyungWook , Lee Young Soo , Joung Boyoung 
Published: June 2023

Abstract
Background
The prognostic significance of resting heart rate and its therapeutic target in atrial fibrillation (AF) is uncertain. We sought to investigate the relationship between resting heart rate and cardiovascular outcomes in patients with non-paroxysmal AF (non-PAF).

Methods
In this propensity score-weighted, multi-center prospective cohort study, 3217 patients with non-PAF were analyzed. Patients were categorized according to the baseline resting heart rate and cardiovascular outcomes were accessed for a median follow-up of 30 months. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and myocardial infarction/critical limb ischemia.

Results
Freedom from primary outcome was longest among patients with resting heart rate 80–99 beats per minute (bpm) whereas shortest among those with ≤ 59 bpm (weighted log rank, p = 0.008). Compared with heart rate ≥ 100 bpm, resting heart rate 80–99 and 60–79 bpm was associated with reduced risk of primary outcome (weighted hazard ratio [WHR] 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.008 and WHR 0.58, 95% CI 0.37–0.92, p = 0.021 for heart rate 80–99 and 60–79 bpm, respectively). Using weighted restricted cubic spline curves, there was a U-shaped association between the resting heart rate and primary outcome with reduced risk of primary outcome in heart rate range of 68–99 bpm. This association was maintained regardless of atrioventricular node (AVN) blocker use or persistent/permanent AF (p for interaction 0.767 for AVN blocker use and 0.720 for AF type).

Conclusion
Resting heart rate was associated with cardiovascular outcomes in patients with non-PAF and those with resting heart rate between 68 and 99 bpm had lower risk of adverse cardiovascular events regardless of AVN blocker use or persistent/permanent AF.
The role of telemedicine in healthcare: an overview and update
Authors: Stoltzfus Mason , Kaur Arshdeep , Chawla Avantika , Gupta Vasu , Anamika F. N. U. , Jain Rohit 
Published: June 2023

Abstract
Background
First implemented in the 1950s, telemedicine is a rapidly evolving tool for healthcare systems around the world. Technological advancement and increasing access to information technology have made the implementation of telemedicine more feasible. Recent provisions by healthcare governing bodies have increased reimbursement for and the use of telemedicine globally. We have done a literature review to find out the pros and cons of adopting telemedicine.

Main body
Telemedicine is found to offer many benefits to conventional, in-person healthcare encounters for both patients and providers: decreased travel cost and time, decreased time spent in waiting rooms, decreased risk of transmission of communicable diseases, decreased overall encounter time consumption, increased convenience, and more. Telemedicine also facilitates seamless transitions of care between healthcare teams, connects isolated people groups with healthcare providers, and helps address regional healthcare infrastructure and provider shortages by connecting patients with healthcare teams from any location. Drawbacks specific to telemedicine include the lack of accessibility and advancement of imaging technology required to replace in-person physical examinations, nonuniversal access to the required devices and networks across the general patient population, and the risk of technical difficulties such as network connection disruptions.

Conclusion
Telemedicine helps bridging the gap of distance by connecting patients in remote locations with the physicians. This has also become vital in the time pandemic.
Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease
Authors: Kahaly George J , Dolman Peter J , Wolf Jan , Giers Bert C , Elflein Heike M , Jain Amy P , Srinivasan Ashok , Hadjiiski Lubomir , Jordan David , Bradley Elizabeth A , Stan Marius N , Eckstein Anja , Pitz Susanne , Vorländer Christian , Wester Sara T , Nguyen John , Tucker Nancy , Sales-Sanz Marco , Feldon Steven E , Nelson Christine C , Hardy Isabelle , Abia-Serrano Maravillas , Tedeschi Philip , Janes Jonathan M , Xu Jing , Vue Peter , Macias William L , Douglas Raymond S 
Published: June 2023

AbstractContextInhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).ObjectiveWe report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.DesignProof-of-concept (POC) and randomized, double-blind placebo-controlled trials.SettingMulticenter.ParticipantsPatients with moderate-to-severe, active TED.InterventionIn the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.Main OutcomeChange from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).ResultsThe randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P &lt; .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P &lt; .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P &lt; .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.ConclusionsThese results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.
Development of Spinal Enthesopathies in Adults With X-linked Hypophosphatemia
Authors: Herrou Julia , Fechtenbaum Jacques , Rothenbuhler Anya , Kamenický Peter , Roux Christian , Linglart Agnès , Briot Karine 
Published: June 2023

Abstract

Context
Musculoskeletal complications are the main manifestations in adults with X-linked hypophosphatemia (XLH). Enthesopathy significantly impairs quality of life.

Objective
To identify the risk factors associated with the development and progression of spinal enthesopathies in adults with XLH.

Design and setting
We conducted a retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism.

Patients
Adults XLH patients with 2 EOS® imaging performed at least 2 years apart at the same center between June 2011 and March 2022. The progression of enthesopathies was defined as a new enthesopathy at least 1 intervertebral level in patients with or without presence of enthesopathy at baseline.

Main outcome measures
Demographic, treatment, PHEX mutation with the progression of enthesopathies.

Results
Fifty-one patients (66.7% of women, mean age 42.1 ± 13.4 years) underwent 2 EOS imaging with an average interval of 5.7 (± 2.31) years.
Progression of spinal enthesopathies was observed in 27 (52.9%) patients. In univariate analysis, patients with a progression of spinal enthesopathies were significantly older (P &lt; .0005), were significantly older at treatment initiation (P = .02), presented with dental complications (P = .03), received less frequently treatment during childhood with phosphate and/or vitamin D analogs (P = .06), and presented more frequently with hip osteoarthritis (P = .002) at baseline. In multivariate analysis, none of these factors was associated with a progression of spinal enthesopathies.

Conclusion
This study confirms the high proportion of patients with a progression of spinal enthesopathies. Age seems to be the main factor associated with progression.
Mutations in cdon and boc affect trunk neural crest cell migration and slow-twitch muscle development in zebrafish
Authors: Lencer Ezra , Rains Addison , Binne Erin , Prekeris Rytis , Artinger Kristin B. 
Published: June 2023

ABSTRACT
The transmembrane proteins cdon and boc are implicated in regulating hedgehog signaling during vertebrate development. Recent work showing roles for these genes in axon guidance and neural crest cell migration suggest that cdon and boc may play additional functions in regulating directed cell movements. We use newly generated and existing mutants to investigate a role for cdon and boc in zebrafish neural crest cell migration. We find that single mutant embryos exhibit normal neural crest phenotypes, but that neural crest migration is strikingly disrupted in double cdon;boc mutant embryos. We further show that this migration phenotype is associated with defects in the differentiation of slow-twitch muscle cells, and the loss of a Col1a1a-containing extracellular matrix, suggesting that neural crest defects may be a secondary consequence to defects in mesoderm development. Combined, our data add to a growing literature showing that cdon and boc act synergistically to promote hedgehog signaling during vertebrate development, and suggest that the zebrafish can be used to study the function of hedgehog receptor paralogs.
The phosphatase Glc7 controls the eisosomal response to starvation via post-translational modification of Pil1
Authors: Paine Katherine M. , Laidlaw Kamilla M. E. , Evans Gareth J. O. , MacDonald Chris 
Published: June 2023

ABSTRACT
The yeast (Saccharomyces cerevisiae) plasma membrane (PM) is organised into specific subdomains that regulate surface membrane proteins. Surface transporters actively uptake nutrients in particular regions of the PM where they are also susceptible to substrate-induced endocytosis. However, transporters also diffuse into distinct subdomains termed eisosomes, where they are protected from endocytosis. Although most nutrient transporter populations are downregulated in the vacuole following glucose starvation, a small pool is retained in eisosomes to provide efficient recovery from starvation. We find the core eisosome subunit Pil1, a Bin, Amphiphysin and Rvs (BAR) domain protein required for eisosome biogenesis, is phosphorylated primarily by the kinase Pkh2. In response to acute glucose starvation, Pil1 is rapidly dephosphorylated. Enzyme localisation and activity screens suggest that the phosphatase Glc7 is the primary enzyme responsible for Pil1 dephosphorylation. Defects in Pil1 phosphorylation, achieved by depletion of GLC7 or expression of phospho-ablative or phospho-mimetic mutants, correlate with reduced retention of transporters in eisosomes and inefficient starvation recovery. We propose that precise post-translational control of Pil1 modulates nutrient transporter retention within eisosomes, depending on extracellular nutrient levels, to maximise recovery following starvation.
Variation in oxidative status, but not structural and physiological development, associated with changing ontogenetic environments
Authors: Allen Joshua M. , Hodinka Brett L. , Barbera Raven A. , Desjardin Genavieve C. , Williams Tony D. 
Published: June 2023

ABSTRACT
Despite the potential for temporally dependent relationships between trait values and fitness (e.g. as juveniles approach life-stage transitions such as fledging), how developmental stage affects canalization (a measure of robustness to environmental variation) of morphological and physiological traits is rarely considered. To test the sensitivity of morphological and physiological traits to environmental variation in two developmental stages, we manipulated brood size at hatch in European starlings (Sturnus vulgaris) and cross-fostered chicks between enlarged and reduced broods approaching fledging. We measured body size (mass, tarsus, wing length) and physiological state (aerobic capacity, oxidative status) at asymptotic mass on day 15, then cross-fostered chicks between ‘high’ and ‘low’ quality environments and assessed the same traits again on day 20, after 5 days of pre-fledging mass recession. Chicks in reduced broods were heavier at asymptotic mass and had lower reactive oxygen metabolites than enlarged broods, whereas structural size, aerobic capacity and antioxidant capacity were unaffected by experimental brood size. The observed canalization of structural and physiological traits during early development was maintained after cross-fostering, during late development. However, in contrast to early development, antioxidant capacity approaching fledging appeared sensitive to environmental conditions, as trajectories varied by cross-fostering treatment. Elevated reactive oxygen metabolites observed after early development in enlarged brood chicks were maintained after cross-fostering, suggesting that canalized development in low-quality environments could produce oxidative costs that carry over between life stages, even when conditions improve. These data reveal trait-specific relationships between environmental conditions and development, and highlight how natal environment effects may vary by developmental stage.
Clean up Your Theory! Invest in Theoretical Clarity and Consistency for Higher-Impact Research
Authors: von Nordenflycht Andrew 
Published: June 2023

This essay starts from a concern that many empirical researchers undermine their rigorous empirical work by coupling it to unclear and inconsistent theory. I suggest this is because we underestimate the difficulty of achieving theoretical clarity and consistency. I illustrate the problem in detail by cataloging common ways we violate clarity and consistency in the articulation of theoretical constructs and relationships and illustrating these violations with examples from unpublished manuscripts. In addition, I draw on the management literature on theory writing as well as on the dual-process theory of cognition and the philosophy of science to identify and unpack three challenges to clear and consistent theory: the taxing cognitive effort required to turn ambiguous, associative intuition into logical arguments; the impossibility of achieving perfect clarity; and the existence of trade-offs between clarity and other valued qualities of theory, particularly generalizability. The implication is that researchers need to invest not just in empirical rigor but also, in theoretical rigor. Funding: The author’s research is supported in part by the Social Sciences and Humanities Research Council of Canada.
Skeletal discrepancies. Part 2: assessment, aetiology and management of high angle cases
Authors: Durman Kyle , Batsford Hannah , Haworth Jennifer A , Fowler Peter , Ireland Anthony J 
Published: June 2023

This is the second article in a three-part series considering skeletal discrepancies in the vertical and transverse dimensions. Discrepancies in the vertical dimension are a relatively common finding, presenting challenges for the orthodontist in terms of treatment planning, management and relapse. CPD/Clinical Relevance: This article aims to increase awareness of the aetiology and management of patients presenting with increased Frankfort/maxillary mandibular planes angle and anterior lower face height, commonly described as ‘high angle’.