bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of the COVID-19 lockdown on malaria transmission in South Africa
Authors: Maharaj Rajendra , Ward Abigail , Didier Bradley , Seocharan Ishen , Firas Nina , Balawanth Ryleen , Lucero Dominic , Morris Natashia , Shandukani Mbavhalelo , Raswiswi Eric , Malatjie Gillian , Mabunda Erik , Moonasar Devanand 
Published: March 2023

Abstract
Background
For a country such as South Africa which is targeting malaria elimination, mobile and migrant populations pose a substantial risk to importation of malaria parasites. It has been hypothesized that halting cross-border movement of mobile and migrant populations will decrease the importation of malaria, however this option is not a politically, operationally, and financially viable prospect. It has social impacts as well, since families live on either side of the border and preventing travel will challenge family ties. Due to the COVID-19 pandemic and closure of ports of entry (land and air) for non-essential travel into South Africa, a unique opportunity arose to test the hypothesis.

Methodology
An interrupted time series analysis was done to assess whether the post-lockdown trends (April–December 2020) in monthly reported imported and local cases differed from the pre-lockdown trends (January 2015–March 2020). The analysis was conducted separately for KwaZulu-Natal, Mpumalanga, and Limpopo provinces.

Results
On average, imported cases were lower in the post-intervention period in all three provinces, and local cases were lower in Mpumalanga and Limpopo, though no results were statistically significant.

Conclusion
Since population movement continued after the travel restrictions were lifted, border screening with testing and treating should be considered for reducing parasite movement. Another option is reducing malaria cases at the source in neighbouring countries by implementing proven, effective vector and parasite control strategies and through a downstream effect reduce malaria entering South Africa.
Cuproptosis correlates with immunosuppressive tumor microenvironment based on pan-cancer multiomics and single-cell sequencing analysis
Authors: Qin Yan , Liu Yanling , Xiang Xiaoyun , Long Xingqing , Chen Zuyuan , Huang Xiaoliang , Yang Jianrong , Li Wei 
Published: March 2023

AbstractRecent studies suggest that cuproptosis, a novel mode of cell death, may be associated with the development of cancer. However, no studies are showing its role in tumorigenesis, progression, and prognosis. In the present study, we comprehensively analyzed the expression difference, gene variation and methylation modification of cuproptosis-related genes (CRGs) in pan-cancer. Then, Single sample gene set enrichment analysis (ssGSEA) was used to calculate individual cuproptosis scores (CS). The association of CS with copy number variation, clinical features, immune-related genes, TMB, MSI, and tumor immune dysfunction and exclusion (TIDE) was comprehensively assessed. Single-cell transcriptome sequencing (scRNA-seq) to analyze the activation of cuproptosis in the tumor microenvironment. Immunohistochemistry (IHC) were used to validate the expression of cuproptosis hub-gene. Our study shows that CRGs were significantly expressed in a variety of tumors, and CDKN2A had the highest mutation frequency (49%) in all tumors. A significant increase in the CS was observed in most cancers and were associated with poor prognosis in the majority of tumors. CS was significantly negatively correlated with tumor microenvironment scores in more than 10 tumors and positively correlated with PD-L1 in 11 tumors, suggesting involvement in tumor immune escape. scRNA-seq suggests that CRG scores significantly increased in the cancer cells. This study opens avenues for further research on the role of cuproptosis in the occurrence and development of cancer and the development of targeted therapies based on cuproptosis.
NMR derived changes of lipoprotein particle concentrations related to impaired fasting glucose, impaired glucose tolerance, or manifest type 2 diabetes mellitus
Authors: Kalbitzer Tina , Lobenhofer Kristina , Martin Silke , Beck Erlach Markus , Kremer Werner , Kalbitzer Hans Robert 
Published: March 2023

Abstract
Background
Type 2 diabetes mellitus (T2D) and corresponding borderline states, impaired fasting glucose (IFG) and/or glucose tolerance (IGT), are associated with dyslipoproteinemia. It is important to distinguish between factors that cause T2D and that are the direct result of T2D.

Methods
The lipoprotein subclass patterns of blood donors with IFG, IGT, with IFG combined with IGT, and T2D are analyzed by nuclear magnetic resonance (NMR) spectroscopy. The development of lipoprotein patterns with time is investigated by using samples retained for an average period of 6 years. In total 595 blood donors are classified by oral glucose tolerance test (oGTT) and their glycosylated hemoglobin (HbA1c) concentrations. Concentrations of lipoprotein particles of 15 different subclasses are analyzed in the 10,921 NMR spectra recorded under fasting and non-fasting conditions. The subjects are assumed healthy according to the strict regulations for blood donors before performing the oGTT.

Results
Under fasting conditions manifest T2D exhibits a significant concentration increase of the smallest HDL particles (HDL A) combined with a decrease in all other HDL subclasses. In contrast to other studies reviewed in this paper, a general concentration decrease of all LDL particles is observed that is most prominent for the smallest LDL particles (LDL A). Under normal nutritional conditions a large, significant increase of the concentrations of VLDL and chylomicrons is observed for all groups with IFG and/or IGT and most prominently for manifest T2D. As we show it is possible to obtain an estimate of the concentrations of the apolipoproteins Apo-A1, Apo-B100, and Apo-B48 from the NMR data. In the actual study cohort, under fasting conditions the concentrations of the lipoproteins are not increased significantly in T2D, under non-fasting conditions only Apo-B48 increases significantly.

Conclusion
In contrast to other studies, in our cohort of “healthy” blood donors the T2D associated dyslipoproteinemia does not change the total concentrations of the lipoprotein particles produced in the liver under fasting and non-fasting conditions significantly but only their subclass distributions. Compared to the control group, under non-fasting conditions participants with IGT and IFG or T2D show a substantial increase of plasma concentrations of those lipoproteins that are produced in the intestinal tract. The intestinal insulin resistance becomes strongly observable.
Ratiometric electrochemical OR gate assay for NSCLC-derived exosomes
Authors: Meng Fanyu , Yu Wenjun , Niu Minjia , Tian Xiaoting , Miao Yayou , Li Xvelian , Zhou Yan , Ma Lifang , Zhang Xiao , Qian Kun , Yu Yongchun , Wang Jiayi , Huang Lin 
Published: March 2023

AbstractNon-small cell lung cancer (NSCLC) is the most common pathological type of LC and ranks as the leading cause of cancer deaths. Circulating exosomes have emerged as a valuable biomarker for the diagnosis of NSCLC, while the performance of current electrochemical assays for exosome detection is constrained by unsatisfactory sensitivity and specificity. Here we integrated a ratiometric biosensor with an OR logic gate to form an assay for surface protein profiling of exosomes from clinical serum samples. By using the specific aptamers for recognition of clinically validated biomarkers (EpCAM and CEA), the assay enabled ultrasensitive detection of trace levels of NSCLC-derived exosomes in complex serum samples (15.1 particles μL−1within a linear range of 102–108particles μL−1). The assay outperformed the analysis of six serum biomarkers for the accurate diagnosis, staging, and prognosis of NSCLC, displaying a diagnostic sensitivity of 93.3% even at an early stage (Stage I). The assay provides an advanced tool for exosome quantification and facilitates exosome-based liquid biopsies for cancer management in clinics.Graphical Abstract
Establishment and validation of a prognostic nomogram for patients with early-onset stage I–II colon cancer
Authors: Li Dongdong 
Published: March 2023

Abstract
Background
The aims of this study were to establish and validate a nomogram model for predicting the survival of patients with early-onset stage I–II colon cancer (CC).

Methods
Data of eligible patients enrolled from 2012 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly allocated to training and validation groups in a 7:3 ratio. Significant prognostic factors were identified by univariate and multivariate analysis and a nomogram model constructed. The predictive performance of the nomogram was evaluated by the concordance index (C-index), calibration plots, and decision curve analysis.

Results
Our study cohort comprised 3528 early-onset CC patients with stage I–II disease, 2469 of whom were allocated to the training cohort and 1059 to the validation cohort. Race, age, marital status, tumor grade, tumor size, tumor stage (T stage), and chemotherapy were considered the significant predictor by univariate analysis. Race, marital status, and T stage were found to be independent prognostic factors by multivariate analysis. The C-indexes of the nomogram were 0.724 and 0.692 in the training and validation cohorts, respectively. Likewise, the calibration plots showed good agreement regarding the probability of 3- and 5-year observed and nomogram-predicted overall survival in the training group. Decision curve analysis showed that the nomogram model was clinically practical and effective. Moreover, applying the nomogram enabled dividing of the patients into two cohorts with different risk scores. The low-risk group thus created had a better survival than the high-risk group.

Conclusions
We developed and validated a meaningful prognostic nomogram model for patients with early-onset stage I–II CC that clinicians can use to make better decisions for individual patients.
Outcome domains measured in randomized controlled trials of physical activity for older adults: a rapid review
Authors: Mackey Dawn C. , Ekegren Christina L. , Baldwin Claire , Young Peter J. , Gray Samantha M. , Ciok Alex , Wong Angela 
Published: March 2023

Abstract
Background
Toward development of a core outcome set for randomized controlled trials (RCTs) of physical activity (PA) interventions for older adults, the purpose of this study was to identify outcome domains and subdomains (‘what’ was measured) in previously published RCTs of PA for older adults.

Methods
We conducted a rapid review and searched Ovid MEDLINE for recently- published (2015-2021), English-language, RCTs of PA interventions for older adults (mean age 60+ yrs). We limited to articles published in Web of Science top-10 journals in general and internal medicine, geriatrics and gerontology, rehabilitation, and sports science. Two reviewers independently completed eligibility screening; two other reviewers abstracted trial descriptors and study outcomes. We classified study outcomes according to the standard outcome classification taxonomy endorsed by the Core Outcome Measures in Effectiveness Trials Initiative.

Results
Our search yielded 548 articles; 67 articles were eligible to be included. Of these, 82% were efficacy/effectiveness trials, 85% included both male and female participants, and 84% recruited community-dwelling older adults. Forty percent of articles reported on interventions that involved a combination of group and individual PAs, and 60% involved a combination of PA modes (e.g., aerobic, resistance). Trial sample size ranged from 14 to 2157 participants, with median (IQR) of 94 (57-517); 28,649 participants were included across all trials. We identified 21 unique outcome domains, spanning 4/5 possible core areas (physiological/clinical; life impact; resource use; adverse events). The five most commonly reported outcome domains were physical functioning (included in n=51 articles), musculoskeletal and connective tissue (n=30), general (n=26), cognitive functioning (n=16), and emotional functioning/wellbeing (n=14). Under these five outcome domains, we further identified 10 unique outcome subdomains (e.g., fall-related; body composition; quality of life). No outcome domains or subdomains were reported consistently in all RCTs.

Conclusions
We found extensive variability in outcome domains and subdomains used in RCTs of PA for older adults, reflecting the broad range of potential health benefits derived from PA and also investigator interest to monitor a range of safety parameters related to adverse events. This study will inform development of a core outcome set to improve outcome reporting consistency and evidence quality.
Exploring the putative role of PRDM1 and PRDM2 transcripts as mediators of T lymphocyte activation
Authors: Di Zazzo Erika , Rienzo Monica , Casamassimi Amelia , De Rosa Caterina , Medici Nicola , Gazzerro Patrizia , Bifulco Maurizio , Abbondanza Ciro 
Published: March 2023

Abstract
Background
T cell activation and programming from their naïve/resting state, characterized by widespread modifications in chromatin accessibility triggering extensive changes in transcriptional programs, is orchestrated by several cytokines and transcription regulators. PRDM1 and PRDM2 encode for proteins with PR/SET and zinc finger domains that control several biological processes, including cell differentiation, through epigenetic regulation of gene expression. Different transcripts leading to main protein isoforms with (PR +) or without (PR-) the PR/SET domain have been described. Although many studies have established the critical PRDM1 role in hematopoietic cell differentiation, maintenance and/or function, the single transcript contribution has not been investigated before. Otherwise, very few evidence is currently available on PRDM2. Here, we aimed to analyze the role of PRDM1 and PRDM2 different transcripts as mediators of T lymphocyte activation.

Methods
We analyzed the transcription signature of the main variants from PRDM1 (BLIMP1a and BLIMP1b) and PRDM2 (RIZ1 and RIZ2) genes, in human T lymphocytes and Jurkat cells overexpressing PRDM2 cDNAs following activation through different signals.

Results
T lymphocyte activation induced an early increase of RIZ2 and RIZ1 followed by BLIMP1b increase and finally by BLIMP1a increase. The “first” and the “second” signals shifted the balance towards the PR- forms for both genes. Interestingly, the PI3K signaling pathway modulated the RIZ1/RIZ2 ratio in favor of RIZ1 while the balance versus RIZ2 was promoted by MAPK pathway. Cytokines mediating different Jak/Stat signaling pathways (third signal) early modulated the expression of PRDM1 and PRDM2 and the relationship of their different transcripts confirming the early increase of the PR- transcripts. Different responses of T cell subpopulations were also observed. Jurkat cells showed that the acute transient RIZ2 increase promoted the balancing of PRDM1 forms towards BLIMP1b. The stable forced expression of RIZ1 or RIZ2 induced a significant variation in the expression of key transcription factors involved in T lymphocyte differentiation. The BLIMP1a/b balance shifted in favor of BLIMP1a in RIZ1-overexpressing cells and of BLIMP1b in RIZ2-overexpressing cells.

Conclusions
This study provides the first characterization of PRDM2 in T-lymphocyte activation/differentiation and novel insights on PRDM1 and PRDM2 transcription regulation during initial activation phases.
Exoskeleton-based training improves walking independence in incomplete spinal cord injury patients: results from a randomized controlled trial
Authors: Gil-Agudo Ángel , Megía-García Álvaro , Pons José Luis , Sinovas-Alonso Isabel , Comino-Suárez Natalia , Lozano-Berrio Vicente , del-Ama Antonio J. 
Published: March 2023

Abstract
Background
In recent years, ambulatory lower limb exoskeletons are being gradually introduced into the clinical practice to complement walking rehabilitation programs. However, the clinical evidence of the outcomes attained with these devices is still limited and nonconclusive. Furthermore, the user-to-robot adaptation mechanisms responsible for functional improvement are still not adequately unveiled. This study aimed to (1) assess the safety and feasibility of using the HANK exoskeleton for walking rehabilitation, and (2) investigate the effects on walking function after a training program with it.

Methods
A randomized controlled trial was conducted including a cohort of 23 patients with less than 1 year since injury, neurological level of injury (C2-L4) and severity (American Spinal Cord Injury Association Impairment Scale [AIS] C or D). The intervention was comprised of 15 one-hour gait training sessions with lower limb exoskeleton HANK. Safety was assessed through monitoring of adverse events, and pain and fatigue through a Visual Analogue Scale. LEMS, WISCI-II, and SCIM-III scales were assessed, along with the 10MWT, 6MWT, and the TUG walking tests (see text for acronyms).

Results
No major adverse events were reported. Participants in the intervention group (IG) reported 1.8 cm (SD 1.0) for pain and 3.8 (SD 1.7) for fatigue using the VAS. Statistically significant differences were observed for the WISCI-II for both the “group” factor (F = 16.75, p < 0.001) and “group-time” interactions (F = 8.87; p < 0.01). A post-hoc analysis revealed a statistically significant increase of 3.54 points (SD 2.65, p < 0.0001) after intervention for the IG but not in the CG (0.7 points, SD 1.49, p = 0.285). No statistical differences were observed between groups for the remaining variables.

Conclusions
The use of HANK exoskeleton in clinical settings is safe and well-tolerated by the patients. Patients receiving treatment with the exoskeleton improved their walking independence as measured by the WISCI-II after the treatment.
A focused review of statistical practices for relating radiation dose-volume exposure and toxicity
Authors: McDonald Andrew M. , Schneider Craig S. , Stahl John M. , Oster Robert A. , Popple Richard A. , Mayo Charles S. 
Published: March 2023

Abstract
Purpose
Relating dose-volume histogram (DVH) information to patient outcomes is critical for outcomes research in radiation oncology, but this is statistically challenging. We performed this focused review of DVH toxicity studies to characterize current statistical approaches and determine the need for updated reporting recommendations.

Methods and materials
We performed a focused MEDLINE search to identify studies published in 5 radiation oncology specialty journals that associated dosimetry with toxicity outcomes in humans receiving radiotherapy between 2015 and 2021. Elements abstracted from each manuscript included the study outcome, organs-at-risk (OARs) considered, DVH parameters analyzed, summary of the analytic approach, use of multivariable statistics, goodness-of-fit reporting, completeness of model reporting, assessment of multicollinearity, adjustment for multiple comparisons, and methods for dichotomizing variables. Each study was also assessed for sufficient reporting to allow for replication of results.

Results
The MEDLINE search returned 2,300 studies for review and 325 met the inclusion criteria for the analysis. DVH variables were dichotomized using cut points in 154 (47.4%) studies. Logistic regression (55.4% of studies) was the most common statistical method used to relate DVH to toxicity outcomes, followed by Cox regression (20.6%) and linear regression (12.0%). Multivariable statistical tests were performed in 226 (69.5%) studies; of these, the possibility of multicollinearity was addressed in 47.8% and model goodness-of-fit were reported in 32.6%. The threshold for statistical significance was adjusted to account for multiple comparisons in 41 of 196 (17.1%) studies that included multiple statistical comparisons. Twenty-eight (8.6%) studies were classified as missing details necessary to reproduce the study results.

Conclusions
Current practices of statistical reporting in DVH outcomes suggest that studies may be vulnerable to threats against internal and external validity. Recommendations for reporting are provided herein to guard against such threats and to promote cohesiveness among radiation oncology outcomes researchers.
Precise acetabular positioning, discrepancy in leg length, and hip offset using a new seven-axis robot-assisted total hip arthroplasty system requires no learning curve: a retrospective study
Authors: Tian Run , Duan Xudong , Kong Ning , Wang Kunzheng , Yang Pei 
Published: March 2023

Abstract
Objective
The purpose of the present study was to determine the learning curve for a novel seven-axis robot-assisted total hip arthroplasty (RA-THA) system, and to explore whether it was able to provide greater accuracy in acetabular cup positioning, superior leg length discrepancy (LLD), and hip offset than conventional methods.

Methods
A total of 160 patients in which unilateral THA was performed in the second affiliated Hospital of Xi'an Jiaotong University from July 2021 to September 2022 were studied. The first 80 patients underwent robot-assisted THA, while conventional THA was performed on the subsequent 80 by the same team of experienced surgeons. The learning curve for the RA-THA system was evaluated using cumulative sum (CUSUM) analysis. The demographic data, preoperative clinical data, duration of surgery, postoperative Harris hip score (HHS) and postoperative radiographic data from patients that had conventional THA were compared.

Results
The 80 patients who underwent primary unilateral RA-THA comprised 42 males and 38 females and were followed up for 12 weeks. Using analysis by CUSUM, the learning curve of the RA-THA system could be divided into learning and proficiency phases, the former of which consisted of the first 17 cases. There was no significant difference between the learning and proficiency phases in terms of LLD, hip offset, or accuracy of acetabular prosthesis position in the RA-THA groups. The proportion of acetabular prostheses located in the Lewinnek safe zone was 90.5% in the proficiency group and 77.5% in the conventional group, respectively, a difference that was statistically significant (P < 0.05). The absolute error between target angle and postoperative measured angle of anteversion was statistically significant in the proficiency group and the conventional group((P < 0.05). Postoperative acetabular anteversion and LLD were 19.96 ± 5.68° and 6.00 (5.00) mm in the proficiency group, respectively, and 17.84 ± 6.81° and 8.09 (4.33) mm using conventional surgery, respectively (anteversion: P = 0.049; LLD: P < 0.001).

Conclusions
The surgical team required a learning curve of 17 cases using the RA-THA system to become proficient. There was no learning curve for other parameters, namely LLD, hip offset, or accuracy of acetabular prosthesis positioning. During the proficiency phase, the RA system was superior to conventional THA for control of leg length and accuracy of acetabular cup placement.