bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of FIXUS AI Deep Learning Model for the Detection of Intra-articular Calcaneal Fractures on X-rays
Authors: Taseh Atta , Ghandour Samir , Gholipour Alireza , Sirls Evan , Fenelon Micheka , Waryasz Gregory R. , Guss Daniel , Bejarano-Pineda Lorena , DiGiovanni Christopher W. , Ashkani-Esfahani Soheil , Kwon John Y.
Published: December 2024

Category:

Hindfoot; Trauma

Introduction/Purpose:

Fractures of the calcaneus are the most frequent form of fractures among the tarsal bones. The treatment plan depends on various fracture characteristics, particularly the extension of the fracture line into the subtalar joint surfaces. While X-rays are the primary diagnostic tool, Computed Tomography (CT) scans are often necessary as they provide a more detailed description of these fractures, especially if the articular surfaces are involved. Although informative, CT scans expose patients to higher doses of ionizing radiation, and they might not be readily available in certain settings. This study aims to develop a deep learning model that will first detect calcaneal fractures and then classify the type of fracture based on its extension into the subtalar joint surfaces.

Methods:

A retrospective case-control study was conducted. Patients aged >18 years who sustained a calcaneal fracture were included in the case group, along with the same number of healthy adults for the control group. Various X-ray views of the foot including anterior, posterior, lateral, along with the axial and lateral calcaneal views were obtained. Two experienced orthopaedic researchers screened the dataset and confirmed the type of fracture. Two models were developed using an Inception V3 architecture and a split ratio of 60:20:20 for training, validation, and testing purposes. The first model was designed for fracture detection, and the second one was designed for detecting intra-articular fracture extension, if present. Conventional model metrics including sensitivity, specificity, Youden index, area under the receiver operating characteristic curve (AUC), and F1 score were reported for each model. A p-value below 0.05 was statistically significant. Baseline values are presented in median and interquartile ranges (IQR).

Results:

A total of 1102 individuals (n=551 for each group) with a female-to-male ratio of 1.6:1 were included. Baseline comparisons showed a significant difference in the age of the groups [cases: 55 (IQR 42, 67) years; controls: 62 (IQR 51, 72 years), p-value < 0.001]. The first model for fracture detection demonstrated a high performance with an AUC of 0.99 and a Youden index of 0.96. The intra-articular fracture detection model showed a slightly lower performance with an AUC of 0.97 and a Youden index of 0.88 (Table 1, Figure 1).

Conclusion:

Our study showed promising results with the utility of deep learning methods for detecting calcaneal fractures and classifying intra- vs extra-articular fractures. This algorithm may help facilitate the diagnosis and treatment of patients with suspected calcaneal fractures, serving as a decision-support tool in settings where CT scanning is not available.
Spontaneous Resolution and Asynchronous Onset of Stellate Nonhereditary Idiopathic Foveomacular Retinoschisis in the Contralateral Eye
Authors: Bayram-Suverza Mauricio , Ramírez-Estudillo Abel
Published: December 2024

Purpose: To present a patient with stellate nonhereditary idiopathic foveomacular retinoschisis found with multimodal imaging. Methods: A single case was evaluated. Results: A 70-year-old woman presented with schisis cavities in the outer plexiform layer in the left eye on macular optical coherence tomography. No leakage was detected by fluorescein angiography. After ruling out other causes of nonvasogenic cystoid maculopathy, the patient was diagnosed with stellate nonhereditary idiopathic foveomacular retinoschisis. After 5 years, the best-corrected visual acuity remained stable. The retinoschisis in the left eye had resolved, and cystoid spaces appeared in the lower portion of the macula in the right eye despite the absence of vitreomacular traction. There was no history of ocular procedures or medication use that could have affected the course of the pathology during the intervening period. Conclusions: This case emphasizes the importance of performing multimodal imaging to monitor the characteristics of stellate nonhereditary idiopathic foveomacular retinoschisis as they evolve.
Evaluating Once a Week Maxillary Advancements Using a Distraction Device
Authors: Swan Courtney , Hush Stefanie , Sobol Danielle , Soldanska Magda , Brady Colin , Williams Joseph K.
Published: December 2024

Introduction: Maxillary distraction is often used to correct significant molar Class III malocclusion. We have introduced a modification of the traditional distraction schedule utilizing larger interval distractions once a week under sedation. We hypothesize that this new schedule still allows for successful advancement with limited relapse of the LeFort segment. The underlying principle is that the greatest benefit of maxillary advancement is utilizing the LeFort I segment to expand the soft tissues of the palate and midface. Methods: The modified advancement schedule consisted of the placement of internal distraction devices following a LeFort I osteotomy with an initial advancement of 5 to 8 mm. Thereafter, the patient underwent weekly “interval” advancements under sedation in the operating room. Cephalograms were taken preoperatively, perioperatively, and 6 months after distraction device removal. The cephalometric landmarks were analyzed including SNA and ANB angles as an indicator of maxillary positioning. Results: From June 2021 to September 2023, 13 consecutive patients underwent maxillary advancement with the new interval advancement schedule. Nine patients were found to have all 3 data points required for inclusion in this study. The total distance of advancement averaged 17.2 (±2.9) mm. Patients had an average of 2.7 (±0.7) advancement events. Advancement on the day of surgery averaged 6.7 (±0.8) mm and during each interval advancement event averaged 6.1 (±1.0), 5.2 (±1.6), and 0.5 (±0.5) mm. Conclusion: Modifying the schedule of maxillary distraction from twice daily advancements during the activation phase to weekly advancements with larger interval movements grants acceptable advancement with limited relapse. This new approach to maxillary advancement utilizes both the principles of distraction osteogenesis and soft tissue expansion.
Community-based energy governance and the political: Towards a post-foundational energy democracy
Authors: Koga Hayato , Petrova Saska , Bouzarovski Stefan
Published: December 2024

Community-based energy governance (CEG) is increasingly seen as reconfiguring existing socio-environmental power dynamics, contributing to just and democratic energy transitions. Despite its perceived “positive” implications, CEG has often been instrumentalized, undermining its potential to transform the spatialities of the existing energy system more democratic. By critically reviewing how the concept of community is mobilized regarding CEG, we seek to delineate how this mobilization entails a degree of romanticization. We then offer an alternative conceptualization of community by drawing upon a post-foundational understanding of space and community, particularly theorizations by Jean-Luc Nancy. We argue that understanding CEG through his ontology of “being-with,” which demands a world where every singularity can expose itself, can create a space for the political. In other words, this ontological understanding reconceptualizes CEG as a contingent political disruptibility of the existing order, rather than merely an institution, or politics. This provides a fundamental guideline to avoid instrumental appropriations of the concept of community and grounds more critical conceptualizations of community in energy and environmental geographies. Furthermore, it guides us to understand energy democracy through CEG as a disruptive political sequence of democratization, instead of an institution that is often instrumentalized with a scaling-up discourse.
High-risk MCL: recognition and treatment
Authors: Jain Preetesh , Wang Michael
Published: December 2024

Significant progress in determining the molecular origins and resistance mechanisms of mantle cell lymphoma (MCL) has improved our understanding of the disease’s clinical diversity. These factors greatly impact the prognosis of patients with MCL. Given the dynamic alterations in MCL clones and disease evolution, it is crucial to recognize high-risk prognostic factors at diagnosis and relapse. Clinical factors include a high MCL International Prognostic Index score with a high Ki-67 proliferation index, early disease progression within 24 months of first-line treatment, >3 previous lines of therapy at relapse, and an aggressive (blastoid or pleomorphic) histology. Molecular aberrations include dysregulated cyclin D1, an aberrant SOX11-CD70 axis, upregulated Musashi-2, MYC rearrangement, metabolic reprogramming, and epigenetic changes. Other factors that contribute to high-risk MCL include an immune-depleted microenvironment and clone adaptability with complex chromosomal anomalies and somatic mutations in TP53, NSD2, CCND1, CDKN2A, BIRC3, SP140, KMT2D, NFkBIE, SMARCA4, and NOTCH2. Ultra-high-risk MCL is indicated by the coexistence of multiple high-risk prognostic factors in the relapse setting and can portend very short progression-free survival. As MCL treatments advance toward cellular therapies, resistance to anti-CD19 chimeric antigen receptor T-cell therapy is also observed. These findings necessitate revisiting the prognostic impact of high-risk factors, current management strategies, new bi- and trispecific T-cell engagers, combination therapies, novel therapeutic targets, and next-generation clinical trials for patients with high-risk MCL. This article provides a comprehensive update on recognizing and managing high-risk MCL and encompass current practices and future directions.
How I use noninvasive prenatal testing for red blood cell and platelet antigens
Authors: van 't Oever Renske Marijke , Verweij E.J.T. (Joanne) , De Haas Masja
Published: December 2024

Alloimmunization during pregnancy occurs when a mother produces antibodies against fetal antigens, leading to complications like hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). HDFN involves destruction of fetal red blood cells, potentially causing severe anemia, hydrops fetalis, and fetal death. FNAIT affects fetal platelets and possibly endothelial cells, resulting in risk of intracranial hemorrhage and brain damage. Traditional invasive methods for fetal antigen genotyping, like amniocentesis, carried miscarriage risks. The discovery of cell-free fetal DNA (cff-DNA) in maternal plasma enabled safe, non-invasive prenatal testing (NIPT). Initially used for RhD blood group typing, NIPT now covers various blood group antigens. Advances in technology have further enhanced NIPT's accuracy. Despite challenges such as low cff-DNA fractions and complex genetic variations, NIPT has become essential in managing alloimmunized pregnancies. In NIPT it is important to prevent both false positive results and false negative results. Particularly in the coming decades, more possibilities for personalized antenatal treatment for HDFN and FNAIT cases will become apparent and accurate NIPT blood group antigen typing results are crucial for guiding clinical decisions. In this paper we describe this journey and provide practical tools for the clinic.
Prognostic and therapeutic implications of measurable residual disease levels during remission induction of childhood ALL
Authors: Zhang Weina , Cai Jiaoyang , Wang Xiang , Ma Yani , Zhu Xiaofan , Yu Jie , Xiao Peifang , Gao Ju , Fang Yongjun , Liang Changda , Li Xue , Zhou Fen , Zhai Xiaowen , Xu Xiaoxiao , Tian Xin , Liu Aiguo , Wang Ningling , Zhu Jiashi , Wang Lingzhen , Cheng Frankie Wai Tsoi , Yang Liangchun , Zhang Ge , Cheng Cheng , Yang Jun J. , Shen Shuhong , Li Chi-kong , Li Benshang , Jiang Hua , Pui Ching-Hon
Published: December 2024

We evaluated the prognostic and therapeutic significance of measurable residual disease (MRD) during remission induction in pediatric acute lymphoblastic leukemia (ALL) patients. In the CCCG-ALL-2015 protocol, 7640 patients were categorized into low-, intermediate-, or high-risk groups based on clinical and genetic features. Final risk classification was determined by MRD assessed via flow cytometry on Days 19 and 46 of remission induction, with additional intensified chemotherapy for Day 19 MRD ≥1%. B-ALL patients with negative MRD (<0.01%) on Day 19 or Day 46 had significantly better 5-year event-free survival (EFS) than those with MRD 0.01-0.99%, who in turn had better EFS than patients with MRD ≥1%. Provisional low-risk patients with Day 19 MRD ≥1% but negative Day 46 MRD, reclassified as intermediate-risk, had comparable 5-year EFS to low-risk patients with Day 19 MRD 0.3-0.99% and negative Day 46 MRD (82.5% vs. 83.0%) and better EFS than provisional low-risk patients with MRD on both days (83.0% vs. 72.6%, P<0.001). Similarly, provisional intermediate-risk B-ALL patients with Day 19 MRD ≥1% but negative Day 46 MRD, who received additional therapy, had better 5-year EFS compared to those with Day 19 MRD between 0.3-0.99% (70.7% vs. 53.0%, P<0.001). Among low-risk patients with negative Day 46 MRD, those with negative Day 19 MRD had superior EFS compared to those with positive Day 19 MRD (91.7% vs. 86.1%, P<0.001). Optimal use of Day 19 MRD could improve individualized treatment and outcomes. Chinese Clinical Trial Registry (ChiCTR-IPR-14005706)
Advancing drug development in myelodysplastic syndromes
Authors: Mina Alain , McGraw Kathy L. , Cunningham Lea , Kim Nina , Jen Emily Y. , Calvo Katherine R. , Ehrlich Lori A. , Aplan Peter D. , Garcia-Manero Guillermo , Foran James M. , Garcia Jacqueline S. , Zeidan Amer M. , DeZern Amy E. , Komrokji Rami , Sekeres Mikkael A. , Scott Bart , Buckstein Rena , Tinsley-Vance Sara , Verma Amit , Wroblewski Tanya , Pavletic Steven , Norsworthy Kelly
Published: December 2024

Myelodysplastic syndromes/neoplasms (MDSs) are heterogeneous stem cell malignancies characterized by poor prognosis and no curative therapies outside of allogeneic hematopoietic stem cell transplantation. Despite some recent approvals by the US Food and Drug Administration, (eg, luspatercept, ivosidenib, decitabine/cedazuridine, and imetelstat), there has been little progress in the development of truly transformative therapies for the treatment of patients with MDS. Challenges to advancing drug development in MDS are multifold but may be grouped into specific categories, including criteria for risk stratification and eligibility, response definitions, time-to-event end points, transfusion end points, functional assessments, and biomarker development. Strategies to address these challenges and optimize future clinical trial design for patients with MDS are presented here.
Quasi-Static and Dynamic Collapse Behavior of Circular Foam-Filled Tubes Inspired by Bamboos
Authors: Liu Kai , Yu Zhenhao , Wang Kaiyun , Jing Lin
Published: December 2024

The axial collapse mechanical behavior and energy absorption characteristics of circular foam-filled tubes mimicking the bamboo characteristics under quasi-static and low-velocity impact loads were investigated via experiments and numerical simulations in this study. The crushing deformation process, load-displacement responses, the strain field and temperature field distribution characteristics of foam-filled tubes were explored. The energy absorption mechanism and crashworthiness performance of specimens were evaluated and compared with conventional empty tubes. Effects of ambient temperature on axial collapse behavior and crashworthiness indices were also clarified. The results revealed that the superior energy absorption capacity of foam-filled tubes was attributed to the strengthening effect of bionic joints and the filling effect of aluminium foam. The energy absorption (EA), specific energy absorption (SEA), and other crashworthiness indices of foam-filled tubes under axial impact load were greatly improved than that of quasi-static load. Compared to conventional empty tubes, the foam-filled tube had a larger energy-absorbing effectiveness factor under both quasi-static and dynamic loads. The increased temperature weakens the crashworthiness performance and energy absorption ability of the foam-filled tube. The SEA values ranged from 28.2 J/g to 22.1 J/g for the quasi-static load and 31.9 J/g to 26.3 J/g for the dynamic load when the temperature elevated from −50 ℃ to 100 ℃.
Solid lipid nanoparticles for increased oral bioavailability of acalabrutinib in chronic lymphocytic leukaemia
Authors: Sinha Swagata , Ravi Punna Rao , Somvanshi Makarand , Rashmi S. R.
Published: December 2024

Acalabrutinib (ACP) is a first-line treatment for chronic lymphocytic leukemia but suffers from poor and variable oral bioavailability due to its pH-dependent solubility, CYP3A4 metabolism, and P-gp efflux. Thus, the objective of this study was to improve the solubility and dissolution behaviour, in turn enhancing bioavailability, by formulating solid lipid nanoparticles (SLNs). ACP loaded SLNs (ACP-SLNs) were prepared via solvent-free hot emulsification followed by a double sonication process. A combination of glyceryl di-behenate and stearyl palmitate along with Tween 80 was used as the lipid phase to dissolve ACP. A 1% w/v Poloxomer188 solution served as the aqueous phase. The optimized ACP-SLNs were spherical in shape and had particle size of 234.7–257.5 nm, PDI of 0.261–0.320 and loading efficiency of 18.70 ± 1.78%. A typical biphasic release pattern was observed from ACP-SLNs in the in vitro dissolution studies under gastrointestinal and plasma pH conditions (> 90% drug release at pH 4.5 ± 0.2, 6.8 ± 0.2 (representing GIT), and 7.4 ± 0.2 (representing plasma) at 8, 16 and 24 h, respectively). The freeze-dried product was stable when stored at 5 °C for over 6 months. Compared with the bulk drug suspension, the ACP-SLNs suspension resulted in 2.29-fold increase in oral bioavailability and more importantly 2.46-fold increase in the distribution of drug to spleen. Additionally, inhibition of lymph production and flow by administering cycloheximide resulted in 46.01% decrease in the overall absorption of ACP-SLNs, indicating the significance of lymphatic uptake process in the oral absorption of ACP-SLNs.

Graphical Abstract
Sex identification in rainbow trout using genomic information and machine learning
Authors: Kudinov Andrei A. , Kause Antti
Published: December 2024

Sex identification in farmed fish is important for the management of fish stocks and breeding programs, but identification based on visual characteristics is typically difficult or impossible in juvenile or premature fish. The amount of genomic data obtained from farmed fish is rapidly growing with the implementation of genomic selection in aquaculture. In comparison to mammals and birds, ray-finned fishes exhibit a greater diversity of sex determination systems, with an absence of conserved genomic regions. A group of genomic markers located on a standard genotyping array has been reported to potentially be linked with sex determination in rainbow trout. However, the set of markers suitable for sex identification may vary between populations. Sex identification from genomic data is usually performed using probabilistic methods, where suitable markers are known beforehand. In our study, we demonstrated the use of the Extreme Gradient Boosting approach from the supervised machine learning gradient boost framework to predict sex from unimputed genomic data, when the suitability of the markers was unknown a priori. The accuracy of the method was assessed using four simulated datasets with different genotyping error rates and one real dataset from the Finnish Rainbow Trout Breeding Program. The method showed high prediction quality on both simulated and real datasets. For simulated datasets with low (5%) and high (50%) genotyping error rates, the accuracies were 1.0 and 0.60, respectively. In the real data, the method achieved a prediction accuracy of 98%, which is suitable for routine use.
Predicting kidney graft function and failure among kidney transplant recipients
Authors: Yao Yi , Astor Brad C. , Yang Wei , Greene Tom , Li Liang
Published: December 2024

Background

Graft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history. Finally, the model should also properly account for the competing risk by death with a functioning graft. A model with the features above is not yet available in the literature and is the focus of this research.

Methods

We built and internally validated a prediction model on 3,893 patients from the Wisconsin Allograft Recipient Database (WisARD) who had a functioning graft 6 months after kidney transplantation. The landmark analysis approach was used to build a proof-of-concept dynamic prediction model to address the aforementioned methodological issues: the prediction of graft failure, accounted for competing risk of death, as well as the future eGFR value, are updated at each post-transplant time. We used 21 predictors including recipient characteristics, donor characteristics, transplant-related and post-transplant factors, longitudinal eGFR, hospitalization, and rejection history. A sensitivity analysis explored a less conservative variable selection rule that resulted in a more parsimonious model with reduced predictors.

Results

For prediction up to the next 1 to 5 years, the model achieved high accuracy in predicting graft failure, with the AUC between 0.80 and 0.95, and moderately high accuracy in predicting eGFR, with the root mean squared error between 10 and 18 mL/min/1.73m2 and 70%-90% of predicted eGFR falling within 30% of the observed eGFR. The model demonstrated substantial accuracy improvement compared to a conventional prediction model that used only baseline predictors.

Conclusion

The model outperformed conventional prediction model that used only baseline predictors. It is a useful tool for patient counseling and clinical management of KTx and is currently available as a web app.
The association between PM2.5 and frailty: evidence from 122 cities in China and 7 countries in Europe
Authors: Wen Yanchao , Zhu Guiming , Cao Kexin , Liang Jie , Lu Xiangfeng , Wang Tong
Published: December 2024

Background

The accelerated aging process worldwide is placing a heavy burden on countries. PM2.5 particulate matter exposure is a significant factor affecting human health and is crucial in the aging process.

Methods

We utilized data from China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Aging, and Retirement in Europe (SHARE) to study the relationship between PM2.5 exposure and the frailty index. Acquire PM2.5 exposure data for China and Europe, match them according to geographic location within the database. Our study used frailty index to evaluate frailty, which comprises 29 items. We examined the association between PM2.5 and frailty index using fixed-effects regression models and Mendelian randomization (MR) analysis.

Results

We first examined the association between PM2.5 and frailty index using fixed-effects regression models, revealing a notable positive link across populations in China (coefficient = 0.0003, P = 0.0380) and Europe (Coefficient = 0.0019, P < 0.0001). This suggests that PM2.5 exposure is a significant risk factor for frailty, leading to accelerated frailty. Moreover, our MR analysis uncovered a possible causal association (OR = 1.2933, 95%CI: 1.2045–1.3820, P < 0.0001) between PM2.5 exposure and the frailty index.

Conclusions

Our findings indicate that long-term exposure to PM2.5 in the environment is a risk factor for physical frailty and may have a potential causal relationship. Given the rapid global aging trend, public health measures are needed to reduce PM2.5 concentrations and prevent frailty.
Application of 3D-printed porous prosthesis for the reconstruction of infectious bone defect with concomitant severe soft tissue lesion: a case series of 13 cases
Authors: Chen Zhuo , Yang Yiyuan , Liu Bingchuan , Li Xingcai , Tian Yun
Published: December 2024

Background

Treating infectious bone defects combined with large soft-tissue lesions poses significant clinical challenges. Herein, we introduced a modified two-stage treatment approach involving the implantation of 3D-printed prostheses and flap repair to treat large segmental infectious tibial bone defects.

Method

We conducted a retrospective study of 13 patients treated at our center between April 2018 and March 2022 for tibial infections owing to posttraumatic infection and chronic osteomyelitis combined with soft tissue defects. The average defect length was 14.0 cm (range, 5.7–22.9 cm). The flap area ranged from 14 × 5 to 15 × 8 + 25 × 15 cm. Sural neurocutaneous, lesser saphenous neurocutaneous, and local fasciocutaneous flaps were used to repair the skin defects. In the second stage, 3D-printed prostheses were designed and implanted. Union rate, complications, and functional outcomes were assessed at the final follow-up.

Result

The average follow-up period was 31.1 months (range, 17–47 months), with an average interval of 208.1 days (range, 139–359 days) between the two stages. According to our criteria, 7 of the 13 patients achieved radiographic healing without intervention. Two patients developed prosthesis-related complications and underwent revision surgery. Two patients experienced recurrent infections leading to prosthesis removal and debridement surgery, with the infection ultimately eradicated in one and the other undergoing amputation. Three patients experienced noninfectious flap-related complications, however, all eventually healed through surgical intervention.

Conclusion

The use of 3D-printed porous titanium prostheses combined with flap soft-tissue repair for the treatment of infectious tibial bone defects did not increase the rate of infection recurrence and provided good functional recovery, offering more options for the treatment of infectious bone defects.
Training needs of German healthcare professionals regarding sexual health and sex workers: results of a nationwide, cross-sectional survey
Authors: Reinehr Sabrina , Neuendorff Nina R. , van der Veen Raquel , Langenbach Benedikt P. , Thieme Andreas
Published: December 2024

Background

Sexual health is an important aspect of human well-being. In terms of sexual health and healthcare, sex workers might need more specialized care than others, given their higher risk for both discrimination and various sexually transmitted diseases. However, little is known about the quality of healthcare professionals’ training regarding sexual health and healthcare of sex workers in Germany.

Methods

In an online survey, 130 physicians, 63 psychotherapists, and 154 medical students reported their perceived quality of training regarding sexual health problems in all their patients and regarding sex workers’ health issues specifically.

Results

A substantial share of respondents reported to have experienced inadequate training regarding both sexual health problems in general and specific issues concerning sex workers. However, most respondents reported feeling rather comfortable when dealing with these topics. There was a positive correlation between feeling comfortable when treating sexual health problems/ sex workers and the perceived training on these topics.

Conclusions

The results of this study indicate that sexual health issues and sex workers’ specific healthcare requirements are not sufficiently addressed in the curricula of German healthcare professionals. Future adaptations of these curricula might be necessary.
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

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

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

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

Cryptococcal 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

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

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

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

N-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.