bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focus group-supported development and psychometric exploration of an instrument to assess perceived physical exertion in nursing students
Authors: Lorenz Eva , Grüne Eva , Popp Johanna , Pfeifer Klaus , Carl Johannes 
Published: December 2024

Abstract
Background
The physical demands of nurses during their work and education are high. In addition, shortage in nursing staff increases the individual workload. However, an appropriate tool to measure perceived physical exertion in nursing students is missing. Therefore, the goal of the present study was to design a questionnaire to assess perceived physical exertion in nursing students during their vocational education and to explore its factor structure.

Methods
We initially conducted two parallel semi-structured focus group interviews with purposefully sampled nursing students to gain insights into their daily physical load. We coded the material and derived an initial set of 35 items (work-related and school-related). Subsequently, we conducted another semi-structured focus group interview with purposefully sampled nursing students of another school to cross-validate the items and refine the preliminary questionnaire according to their responses. To check the psychometric quality and factor structure of the questionnaire, we used data of 237 nursing students from 16 different nursing schools. We analyzed the items (n = 30) descriptively (including internal consistency via Cronbach’s α) and examined the structure of the questionnaire using exploratory factor analyses.

Results
In the focus group interviews, we found different categories that play a role for perceived physical exertion in nursing vocational education: ‘general conditions’, ‘patient’, ‘additional load’, ‘locomotion’, ‘awkward postures’, ‘one-sided load’ and ‘others’. The factor analyses suggested three factors explaining the structure of the questionnaire. We registered satisfactory item statistics and good internal consistencies for all three factors: ‘relocating and handling of objects’ (α = 0.967); ‘personal care of patients’ (α = 0.910); ‘relocating patients’ (α = .809). The final questionnaire comprises 30 items (28 work-related, two school-related).

Conclusion
The developed questionnaire provided initial evidence for content validity and internal consistency of the factors. The instrument can be used to detect perceived physical exertion in nursing students and thus help specifically address health-related problems. There is a need for a further confirmatory approach to cross-validate the questionnaire.

Trail registration
Clinical trials NCT05817396.
A single-plasmid-based, easily curable CRISPR/Cas9 system for rapid, iterative genome editing in Pseudomonas putida KT2440
Authors: Wen Qifeng , Chen JinJin , Li Jin , Dharmasiddhi Ida Putu Wiweka , Yang Maohua , Xing Jianmin , Liu Yilan 
Published: December 2024

Abstract
Background
Pseudomonas putida KT2440, a non-pathogenic soil bacterium, is a key platform strain in synthetic biology and industrial applications due to its robustness and metabolic versatility. Various systems have been developed for genome editing in P. putida, including transposon modules, integrative plasmids, recombineering systems, and CRISPR/Cas systems. However, rapid iterative genome editing is limited by complex and lengthy processes.

Results
We discovered that the pBBR1MCS2 plasmid carrying the CRISPR/Cas9 module could be easily cured in P. putida KT2440 at 30 oC. We then developed an all-in-one CRISPR/Cas9 system for yqhD and ech-vdh-fcs deletions, respectively, and further optimized the editing efficiency by varying homology arm lengths and target sites. Sequential gene deletions of vdh and vanAB were carried out rapidly using single-round processing and easy plasmid curing. This system’s user-friendliness was validated by 3 researchers from two labs for 9 deletions, 3 substitutions, and 2 insertions. Finally, iterative genome editing was used to engineer P. putida for valencene biosynthesis, achieving a 10-fold increase in yield.

Conclusions
We developed and applied a rapid all-in-one plasmid CRISPR/Cas9 system for genome editing in P. putida. This system requires less than 1.5 days for one edit due to simplified plasmid construction, electroporation and curing processes, thus accelerating the cycle of genome editing. To our knowledge, this is the fastest iterative genome editing system for P. putida. Using this system, we rapidly engineered P. putida for valencene biosynthesis for the first time, showcasing the system’s potential for expanding biotechnological applications.
Effectiveness of an online food shopping intervention to reduce salt purchases among individuals with hypertension – findings of the SaltSwitch Online Grocery Shopping (OGS) randomised trial
Authors: Wu Jason HY , Maganja Damian , Huang Liping , Trieu Kathy , Taylor Fraser , Barrett Eden M. , Arnott Clare , Feng Xiaoqi , Schutte Aletta E. , Di Tanna Gian Luca , Mhurchu Cliona Ni , Cameron Adrian J. , Huffman Mark D. , Neal Bruce 
Published: December 2024

Abstract
Background
Online grocery shopping is a growing source of food purchases in many countries. We investigated the effect of nudging consumers towards purchases of lower sodium products using a web browser extension.

Methods
This trial was conducted among individuals with hypertension who shopped for their groceries online in Australia. From July 2021 to June 2023, participants were randomised to use the SaltSwitch Online Grocery Shopping web browser extension or continue their usual grocery shopping for 12 weeks. The SaltSwitch extension modified a retailer’s online shopping interface to suggest similar but lower sodium alternative products to those initially selected. The primary outcome was the difference in mean sodium density (mg sodium per 1000 kcal of energy) of packaged food purchases between the intervention and control groups.

Results
We randomised 185 participants of average age 56.0 (SD 11.0) years. Most were women (64%), White (89%), had BMI > 25 kg/m2 (91%), and were taking anti-hypertensive medication (83%). Demographic and medical characteristics were similar across the randomised groups. 182 (98%) completed the trial. Over the 12-week intervention, the sodium density of groceries purchased by the intervention group compared to the control group was 204 mg/1000 kcal lower (95%CI, -352 to -56) (P = 0.01). The reduction in sodium density of purchases was apparent in weeks 1–4 and sustained through the end of the trial. 86% of participants in the intervention group made at least one switch to a lower sodium product. There were no detectable effects on blood pressure, spot urine sodium concentration, or other secondary outcomes across the 12-week study period.

Conclusions
Online shopping platforms provide a novel opportunity to support purchases of lower sodium foods. While the reductions in sodium density of purchases were moderate in size, population health benefits could nonetheless be large if they were sustained over time and at scale, with large and growing numbers of online grocery shoppers and a high prevalence of elevated blood pressure amongst adults.

Trial registration
ACTRN12621000642886.
Determination of cryptococcal antigen in newly diagnosed HIV infected patients attending Specialist Hospital Sokoto North-Western Nigeria
Authors: Usman Abubakar Babangida , Yau Yassar Muhammad , Ibrahim Adamu Muhammad , Folashade Salaudeen Zainab , Abdullahi Hamisu , Hamid Kabir Magaji 
Published: December 2024

AbstractCryptococcal Meningitis (CM), an infection and inflammation of the meninges, predominantly affects individuals with compromised immune systems, particularly HIV/AIDS patients. This study aims to assess the CD4 count of newly diagnosed HIV patients, prevalence of cryptococcal antigen in those with low CD4 counts, and socioeconomic risk factors associated with cryptococcal diseases in Sokoto, Nigeria. A cross-sectional study was conducted among 154 newly diagnosed HIV-positive patients at Specialist Hospital Sokoto, utilizing blood samples for CD4 count and cryptococcal antigen detection via lateral flow assay. The study found that 38.2% of patients with CD4 < 200 cells/µL were positive for cryptococcal antigen, highlighting a significant association between low CD4 count and cryptococcal infection (p value 0.000). The prevalence was highest among the 31–40 years age group (47.6%) and married individuals (61.9%), although no significant associations were found with age or marital status. Socioeconomic factors revealed higher prevalence among Hausa/Fulani (85.7%) and individuals with informal education (66.7%). The study underscores the necessity of routine cryptococcal antigen screening in HIV clinics to reduce CM-related morbidity and mortality. Early diagnosis and preventive interventions are crucial to address the substantial burden of cryptococcal infection among HIV patients in Sokoto State, Nigeria.
Integrated hepatic transcriptomics and metabolomics identify Pck1 as a key factor in the broad dysregulation induced by vehicle pollutants
Authors: Ramanathan Gajalakshmi , Zhao Yuqi , Gupta Rajat , Langmo Siri , Bhetraratana May , Yin Fen , Driscoll Will , Ricks Jerry , Louie Allen , Stewart James A. , Gould Timothy R. , Larson Timothy V. , Kaufman Joel , Rosenfeld Michael E. , Yang Xia , Araujo Jesus A. 
Published: December 2024

Abstract
Background
Exposure to air pollution is associated with worldwide morbidity and mortality. Diesel exhaust (DE) emissions are important contributors which induce vascular inflammation and metabolic disturbances by unknown mechanisms. We aimed to determine molecular pathways activated by DE in the liver that could be responsible for its cardiometabolic toxicity.

Methods
Apolipoprotein E knockout (ApoE KO) mice were exposed to DE or filtered air (FA) for two weeks, or DE for two weeks followed by FA for 1 week. Expression microarrays and global metabolomics assessment were performed in the liver. An integrated transcriptomic and metabolomic analytical strategy was employed to dissect critical pathways and identify candidate genes that could dissect DE-induced pathogenesis. HepG2 cells were treated with an organic extract of DE particles (DEP) vs. vehicle control to test candidate genes.

Results
DE exposure for 2 weeks dysregulated 658 liver genes overrepresented in whole cell metabolic pathways, especially including lipid and carbohydrate metabolism, and the respiratory electron transport pathway. DE exposure significantly dysregulated 118 metabolites, resulting in increased levels of triglycerides and fatty acids due to mitochondrial dysfunction as well as increased levels of glucose and oligosaccharides. Consistently, DEP treatment of HepG2 cells led to increased gluconeogenesis and glycogenolysis indicating the ability of the in-vitro approach to model effects induced by DE in vivo. As an example, while gene network analysis of DE livers identified phosphoenolpyruvate carboxykinase 1 (Pck1) as a key driver gene of DE response, DEP treatment of HepG2 cells resulted in increased mRNA expression of Pck1 and glucose production, the latter replicated in mouse primary hepatocytes. Importantly, Pck1 inhibitor mercaptopicolinic acid suppressed DE-induced glucose production in HepG2 cells indicating that DE-induced elevation of hepatic glucose was due in part to upregulation of Pck1 and increased gluconeogenesis.

Conclusions
Short-term exposure to DE induced widespread alterations in metabolic pathways in the liver of ApoE KO mice, especially involving carbohydrate and lipid metabolism, together with mitochondrial dysfunction. Pck1 was identified as a key driver gene regulating increased glucose production by activation of the gluconeogenesis pathway.
Dynamic assessment of signal entropy for prognostication and secondary brain insult detection after traumatic brain injury
Authors: Bögli Stefan Yu , Olakorede Ihsane , Beqiri Erta , Chen Xuhang , Ercole Ari , Hutchinson Peter , Smielewski Peter 
Published: December 2024

Abstract
Background
Entropy quantifies the level of disorder within a system. Low entropy reflects increased rigidity of homeostatic feedback systems possibly reflecting failure of protective physiological mechanisms like cerebral autoregulation. In traumatic brain injury (TBI), low entropy of heart rate and intracranial pressure (ICP) predict unfavorable outcome. Based on the hypothesis that entropy is a dynamically changing process, we explored the origin and value of entropy time trends.

Methods
232 continuous recordings of arterial blood pressure and ICP of TBI patients with available clinical information and 6-month outcome (Glasgow Outcome Scale) were accessed form the Brain Physics database. Biosignal entropy was estimated as multiscale entropy (MSE) that aggregates entropy at several time scales (20 coarse graining steps starting from 0.1 Hz). MSE was calculated repeatedly for consecutive, overlapping 6 h segments. Percentage monitoring time (ptime) or dosage (duration*level/hour) below different cutoffs were evaluated against outcome using univariable and multivariable analyses, and propensity score matching. Associations to clinical and monitoring metrics were explored using correlation coefficients. Lastly, individual secondary brain insults (deviations in ICP, cerebral perfusion pressure – CPP, or pressure reactivity) were assessed in relation to changes in MSE.

Results
Increased MSE abp and MSE cpp ptime (OR 1.28 (1.07–1.58) and OR 1.50 (1.16–2.03) for MSE abp and cpp respectively) and dose (OR 1.12 (1.02–1.27) and OR 1.21 (1.06–1.46) for MSE abp and cpp respectively) were associated with poor outcome even after propensity score matching within multivariable models correcting for ICP, CPP, and the pressure reactivity index. MSE trajectories differed significantly dependent on outcome. The entropy metrics displayed weak correlations to clinical parameters. Individual episodes of deranged physiology were associated with decreases in the MSE metrics from both cerebral and systemic biosignals.

Conclusions
Biosignal entropy of changes dynamically after TBI. The assessment of these variations augments individualized, dynamic, outcome prognostication and identification of secondary cerebral insults. Additionally, these explorations allow for further exploitation of the extensive physiological data lakes acquired for each TBI patient within an intensive care environment.
The evolutionary history of Plasmodium falciparum from mitochondrial and apicoplast genomes of China-Myanmar border isolates
Authors: Tian Yini , Ye Run , Zhang Dongmei , Zhang Yilong 
Published: December 2024

Abstract
Background
The frequent communication between African and Southeast Asian (SEA) countries has led to the risk of imported malaria cases in the China-Myanmar border (CMB) region. Therefore, tracing the origins of new malaria infections is important in the maintenance of malaria-free zones in this border region. A new genotyping tool based on a robust mitochondrial (mt) /apicoplast (apico) barcode was developed to estimate genetic diversity and infer the evolutionary history of Plasmodium falciparum across the major distribution ranges. However, the mt/apico genomes of P. falciparum isolates from the CMB region to date are poorly characterized, even though this region is highly endemic to P. falciparum malaria.

Methods
We have sequenced the whole mt/apico genome of 34 CMB field isolates and utilized a published data set of 147 mt/apico genome sequences to present global genetic diversity and to revisit the evolutionary history of the CMB P. falciparum.

Results
Genetic differentiation based on mt/apico genome of P. falciparum revealed that the CMB (Lazan, Myanmar) isolates presented high genetic diversity with several characteristics of ancestral populations and shared many of the genetic features with West Thailand (Mae Sot; WTH) and to some extent West African (Banjul, Gambia; Navrongo, Ghana; WAF) isolates. The reconstructed haplotype network displayed that the CMB and WTH P. falciparum isolates have the highest representation (five) in the five ancestral (central) haplotypes (H1, H2, H4, H7, and H8), which are comparatively older than isolates from other SEA populations as well as the WAF populations. In addition, the highest estimate of the time to the Most Recent Common Ancestor (TMRCA) of 42,400 (95% CI 18,300–82100) years ago was presented by the CMB P. falciparum compared to the other regional populations. The statistically significant negative values of Fu's Fs with unimodal distribution in pairwise mismatch distribution curves indicate past demographic expansions in CMB P. falciparum with slow population expansion between approximately 12,500–20,000 ybp.

Conclusions
The results on the complete mt/apico genome sequence analysis of the CMB P. falciparum indicated high genetic diversity with ancient population expansion and TMRCA, and it seems probable that P. falciparum might have existed in CMB, WTH, and WAF for a long time before being introduced into other Southeast Asian countries or regions. To reduce the impact of sample size or geographic bias on the estimate of the evolutionary timeline, future studies need to expand the range of sample collection and ensure the representativeness of samples across geographic distributions. Additionally, by mapping global patterns of mt/apico genome polymorphism, we will gain valuable insights into the evolutionary history of P. falciparum and optimised strategies for controlling P. falciparum malaria at international borders.

Graphical Abstract
Unraveling the protein kinase C/NDRG1 signaling network in breast cancer
Authors: Saponaro C. , Damato M. , Stanca E. , Aboulouard S. , Zito F. A. , De Summa S. , Traversa D. , Schirosi L. , Bravaccini S. , Pirini F. , Fonzi E. , Tebaldi M. , Puccetti M. , Gaballo A. , Pantalone L. , Ronci M. , Magnani L. , Sergi D. , Tinelli A. , Tacconi S. , Siculella L. , Giudetti A. M. , Fournier I. , Salzet M. , Trerotola M. , Vergara D. 
Published: December 2024

AbstractN-myc downstream-regulated gene 1 (NDRG1) is a member of the NDRG family of intracellular proteins and plays a central role in a wide range of biological processes including stress response, differentiation, and metabolism. The overexpression of NDRG1 is an indicator of poor prognosis in various types of cancer. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC). Analysis of the TCGA dataset showed a significant positive correlation between NDRG1 and PRKCA expression, suggesting a mechanistic role of protein kinase C (PKC) in the regulation of NDRG1. We then assessed the hypothesis that PKC might modulate the activity of NDRG1, and observed that different acute stress conditions converging on PKC activation lead to enhanced NDRG1 expression. This mechanism was found to be specific for NDRG1 as the expression of other NDRG members was not affected. Moreover, CRISPR-based inhibition of NDRG1 expression was obtained in a BC cell line, and showed that this protein is a key driver of BC cell invasion through the Rho-associated coiled-coil containing protein kinase 1 (ROCK1)/phosphorylated cofilin pathway that regulates stress fiber assembly, and the modulation of extracellular matrix reorganization related genes. Together, our findings highlight the potential of NDRG1 as a new BC biomarker and uncover a novel mechanism of regulation of NDRG1 expression that might lead to innovative therapeutic strategies.
CCN3: lactational bone booster
Authors: Xu Nathan , Yang Kyle , Wang Mengjie 
Published: December 2024

AbstractMammalian reproduction requires that nursing mothers transfer large amounts of calcium to their offspring through milk. Meeting this demand requires the activation of a brain-breast-bone circuit during lactation that coordinates changes in systemic hormones, dietary calcium intake, skeletal turnover, and calcium transport into milk. Classically, increased bone resorption via increased parathyroid hormone-related protein and low estrogen levels is the main source of calcium for milk production during lactation. Over the past few decades, investigators have described many aspects of this brain-breast-bone axis during lactation, yet many unanswered questions remain. Using a comprehensive set of parabiosis coupled with in vivo µCT, bone transplant studies, cell culturing and differentiation assays, mouse genetic models, pharmacologic interventions, hepatic viral transduction, and sequencing analysis, a recent study discovered that cellular communication network factor 3 (CCN3), derived from ARHERα/Kiss1 neurons, functions as an osteogenic hormone to sustain bone formation and progeny survival during lactation. Compelling evidence has been presented to show that (1) CCN3 expression in ARHERα/Kiss1 neurons fluctuates, almost exclusively appearing during lactation; (2) CCN3 stimulates mouse and human skeletal stem cell activity, increases bone remodeling and fracture repair in young and old mice of both sexes; (3) knockdown Ccn3 transcripts in the ARHKiss1 neurons in lactating dams causes devastating bone loss and failure to sustain progeny survival. These findings suggested that the stage-specific expression of CCN3 in female ARHERα/Kiss1 neurons during lactation is a newly identified brain-bone axis evolved to sustain the skeleton in mammalian mothers and offspring.
Immobilization of manganese in solution and soil contaminated with trivalent chromium using biochars
Authors: Jee Hyo Kyung , Kim Han Na , Park Jin Hee 
Published: December 2024

AbstractMn (manganese) exists in various oxidation states in soil, and Mn2+ is the most mobile species of Mn, which is toxic to plants and restricts their growth. When soil is contaminated with trivalent chromium (Cr3+), Mn oxides in the soil are reduced to Mn2+ by oxidizing Cr3+ while oxidized Cr is subsequently reduced back to Cr3+ by organic matter in soil, leaving Mn2+ and Cr3+ in the soil. Therefore, the objective of this study was to immobilize Mn2+ without altering the Cr species in the soil and to evaluate the effectiveness of biochar treatment in immobilizing both Mn2+ and Cr³⁺ in Cr³⁺-contaminated soil. Biochars derived from different sources including rice bran (RB), chicken manure (CM) and cow manure (WM) were tested for Mn adsorption and the chicken manure derived-biochar showed the highest removal efficiency (100%) for Mn in Mn solution. Moreover, 100% of both Mn²⁺ and Cr³⁺ were removed in Mn²⁺ and Cr³⁺ mixed solution without oxidizing Cr3+. In Mn2+ and Cr3+ mixed solution, initially 1.7% of Cr³⁺ was oxidized to Cr⁶⁺ by Mn, which was subsequently reduced back to Cr³⁺ by biochar, leading to its complete adsorption. In Cr3+ spiked soils treated with 5% and 10% CM biochar, bioavailable Mn and Cr concentrations were significantly reduced. Therefore, biochar is a promising amendment for reducing the bioavailability of Mn and Cr limiting Cr3+ oxidation in Cr3+ contaminated soils.