bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis
Authors: Li Jicui , Guo Qiaoyan , Wei Xianping , Zhu Yuexin , Luo Manyu , Luo Ping 
Published: January 2024

IntroductionWe aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN.MethodsWe selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states.ResultsThere was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity.ConclusionNrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.
Antagonism of regulatory ISGs enhances the anti-melanoma efficacy of STING agonists
Authors: Filderman Jessica N. , Taylor Jennifer L. , Wang Jianmin , Zhang Yali , Singh Prashant , Ross Mark A. , Watkins Simon C. , Nedal Al Bzour Ayah , Karapetyan Lilit , Kalinski Pawel , Storkus Walter J. 
Published: January 2024

BackgroundStimulator of Interferon Genes (STING) is a dsDNA sensor that triggers type I inflammatory responses. Recent data from our group and others support the therapeutic efficacy of STING agonists applied intratumorally or systemically in a range of murine tumor models, with treatment benefits associated with tumor vascular normalization and improved immune cell recruitment and function within the tumor microenvironment (TME). However, such interventions are rarely curative and STING agonism coordinately upregulates expression of immunoregulatory interferon-stimulated genes (ISGs) including Arg2, Cox2, Isg15, Nos2, and Pdl1 that may limit treatment benefits. We hypothesized that combined treatment of melanoma-bearing mice with STING agonist ADU-S100 together with antagonists of regulatory ISGs would result in improved control of tumor growth vs. treatment with ADU-S100 alone.MethodsMice bearing either B16 (BRAFWTPTENWT) or BPR20 (BRAFV600EPTEN-/-) melanomas were treated with STING agonist ADU-S100 plus various inhibitors of ARG2, COX2, NOS2, PD-L1, or ISG15. Tumor growth control and changes in the TME were evaluated for combination treatment vs ADU-S100 monotherapy by tumor area measurements and flow cytometry/transcriptional profiling, respectively.ResultsIn the B16 melanoma model, we noted improved antitumor efficacy only when ADU-S100 was combined with neutralizing/blocking antibodies against PD-L1 or ISG15, but not inhibitors of ARG2, COX2, or NOS2. Conversely, in the BPR20 melanoma model, improved tumor growth control vs. ADU-S100 monotherapy was only observed when combining ADU-S100 with ARG2i, COX2i, and NOS2i, but not anti-PD-L1 or anti-ISG15. Immune changes in the TME associated with improved treatment outcomes were subtle but included increases in proinflammatory innate immune cells and activated CD8+CD69+ T cells and varied between the two tumor models.ConclusionsThese data suggest contextual differences in the relative contributions of individual regulatory ISGs that serve to operationally limit the anti-tumor efficacy of STING agonists which should be considered in future design of novel combination protocols for optimal treatment benefit.
Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome
Authors: Saito Suguru , Shahbaz Shima , Luo Xian , Osman Mohammed , Redmond Desiree , Cohen Tervaert Jan Willem , Li Liang , Elahi Shokrollah 
Published: January 2024

IntroductionA group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed.MethodsWe identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC).ResultsThrough these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores.ConclusionOur study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.
Cost-effectiveness analysis of toripalimab for metastatic or recurrent triple-negative breast cancer
Authors: Shao Jiangbo , Zhan Cuiping , Jin Chunxiang , Jin Ying 
Published: January 2024

BackgroundToliparibizumab in combination with nab-paclitaxel (T+N) has excellent efficacy inmetastatic or recurrent triple-negative breast cancer (TNBC), but the optimal choice of sequence of therapy is unclear given the trade-offs between quality of life and cost. Cost-effectiveness analyses can quantify these tradeoffs, leading to more informed decisions. Our objective was to assess the societal cost-effectiveness of the T+N regimen for metastatic or recurrent TNBC.MethodsClinical data were extracted from a multicenter, randomized, double-blind trial, TORCHLIGHT (NCT04085276). Patients were randomized into the T+N group or placebo plus nab-paclitaxel (P+N) group. 531 patients from 53 study locations were randomly assigned (T+N, n=353; P+N, n=178) into intend to treat (ITT) population; 200 and 100 patients, respectively had programmed death protein 1 (PD-L1) positive TNBC. A Markov model was established with a 21-day cycle length. Costs were acquired from local hospitals, effect parameters included quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER).ResultsThe cost differences were 47,538.3 CNY in ITT population (T+N, 143,725.67 CNY; P+N group, 96,187.37 CNY) and 29,258.84 CNY in PD-L1+ subgroup (T+N, 100,128.28 CNY; P+N group, 70,869.45 CNY). Meanwhile, the IEs were 0.03409 in the ITT population (T+N, 0.55323 QALY; P+N, 0.51914 QALY) and 0.03409 in the PD-L1+ subgroup (T+N, 0.42327 QALY; P+N, 0.37628 QALY). The ICERs between T+N and P+N groups were 1,394,548.41 CNY/QALY in the ITT population and 622,663.98 CNY/QALY in the PD-L1+ subgroup. We also analyzed the cost-effectiveness of toripalimab could be received in the Chinese medical insurance catalog. If toripalimab could be reimbursed at an 80% rate, the cost differences were changed to 16,598.99 CNY in ITT population (T+N, 112,786.36 CNY; P+N group, 96,187.37 CNY) and 7,704.58 CNY in PD-L1+ subgroup (T+N, 78,574.03 CNY; P+N group, 70,869.45 CNY). Meanwhile, the IEs remained unchanged. The ICERs between T+N and P+N groups were changed to 486,935.82 CNY/QALY in the ITT population and 163,962.96 CNY/QALY in the PD-L1+ subgroup. Sensitivity analyses indicated the stability of the model and the impact of utility.ConclusionAt current drug prices, the T+N group is not more cost-effective than the P+N group, but after incorporating toripalimab into medical insurance, the T+N group will be more cost-effective for patients with PD-L1+ metastatic or recurrent triple-negative breast cancer.
Perceived potentially inappropriate treatment in the PICU: frequency, contributing factors and the distress it triggers
Authors: Sarpal Amrita , Miller Michael R. , Martin Claudio M. , Sibbald Robert W. , Speechley Kathy N. 
Published: January 2024

BackgroundPotentially inappropriate treatment in critically ill adults is associated with healthcare provider distress and burnout. Knowledge regarding perceived potentially inappropriate treatment amongst pediatric healthcare providers is limited.ObjectivesDetermine the frequency and factors associated with potentially inappropriate treatment in critically ill children as perceived by providers, and describe the factors that providers report contribute to the distress they experience when providing treatment perceived as potentially inappropriate.MethodsProspective observational mixed-methods study in a single tertiary level PICU conducted between March 2 and September 14, 2018. Patients 0–17 years inclusive with: (1) ≥1 organ system dysfunction (2) moderate to severe mental and physical disabilities, or (3) baseline dependence on medical technology were enrolled if they remained admitted to the PICU for ≥48 h, and were not medically fit for transfer/discharge. The frequency of perceived potentially inappropriate treatment was stratified into three groups based on degree of consensus (1, 2 or 3 providers) regarding the appropriateness of ongoing active treatment per enrolled patient. Distress was self-reported using a 100-point scale.ResultsOf 374 patients admitted during the study, 133 satisfied the inclusion-exclusion criteria. Eighteen patients (unanimous - 3 patients, 2 providers - 7 patients; single provider - 8 patients) were perceived as receiving potentially inappropriate treatment; unanimous consensus was associated with 100% mortality on 3-month follow up post PICU discharge. Fifty-three percent of providers experienced distress secondary to providing treatment perceived as potentially inappropriate. Qualitative thematic analysis revealed five themes regarding factors associated with provider distress: (1) suffering including a sense of causing harm, (2) conflict, (3) quality of life, (4) resource utilization, and (5) uncertainty.ConclusionsWhile treatment perceived as potentially inappropriate was infrequent, provider distress was commonly observed. By identifying specific factor(s) contributing to perceived potentially inappropriate treatment and any associated provider distress, organizations can design, implement and assess targeted interventions.
Determinants of early neonatal mortality: secondary analysis of the 2012 and 2017 Indonesia Demographic and Health Survey
Authors: Titaley Christiana Rialine , Mu'asyaroh Anifatun , Que Bertha Jean , Tjandrarini Dwi Hapsari , Ariawan Iwan 
Published: January 2024

BackgroundMost neonatal deaths occur during the first week of life (i.e., early neonatal deaths). In this analysis, we aimed to investigate the determinants of early neonatal deaths in a nationally representative sample of births in Indonesia over the five years before each survey.MethodsData were obtained from the 2012 and 2017 Indonesia Demographic and Health Survey (IDHS), including information from 58,902 mothers of children aged &lt;5 years of age. The outcome variable was early neonatal death (death of a newborn within the first six days of life). Explanatory variables were categorized into environmental, household, maternal, pregnancy, childbirth, and child characteristics. Multivariate regression methods were employed for analysis.ResultsIncreased odds of early neonatal deaths were associated with mothers who lacked formal education or had incomplete primary schooling (adjusted odd ratio [OR] = 2.43, 95% confidence interval [CI]: 1.18–5.01), worked outside the house in agricultural (aOR = 5.94, 95% CI: 3.09–11.45) or non-agricultural field (aOR = 2.98, 95% CI: 1.88–4.72), and were required to make a joint decision about health care with their partner or another household member (aOR = 1.79, 95% CI: 1.12–2.84). Increased odds were also observed in smaller-than-average infants, particularly those who received low-quality antenatal care services (aOR = 9.10, 95% CI: 5.04–16.41) and those whose mothers had delivery complications (aOR = 1.72, 95% CI: 1.10–2.68) or who were delivered by cesarean section (aOR = 1.74, 95% CI: 1.07–2.82). Furthermore, male infants showed higher odds than female infants (aOR = 1.85, 95% CI: 1.23–2.76).ConclusionsA multifaceted approach is essential for curtailing early neonatal mortality in Indonesia. Enabling workplace policies, promoting women's empowerment, strengthening the health system, and improving the uptake of high-quality antenatal care services are among the critical steps toward preventing early neonatal deaths in Indonesia.
High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data
Authors: Amniouel Soukaina , Jafri Mohsin Saleet 
Published: January 2024

Introduction: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed.Methods: A newly developed machine learning model was applied on several gene expression data from the public repository GEO database to identify molecular signatures predictive of efficacy of 5-FU based combination chemotherapy (FOLFOX and FOLFIRI) in patients with CRC. The model was trained using 5-fold cross validation and multiple feature selection methods including LASSO and VarSelRF methods. Random Forest and support vector machine classifiers were applied to evaluate the performance of the models.Results and Discussion: For the CRC GEO dataset samples from patients who received either FOLFOX or FOLFIRI, validation and test sets were &gt;90% correctly classified (accuracy), with specificity and sensitivity ranging between 85%-95%. In the datasets used from the GEO database, 28.6% of patients who failed the treatment therapy they received are predicted to benefit from the alternative treatment. Analysis of the gene signature suggests the mechanistic difference between colorectal cancers that respond and those that do not respond to FOLFOX and FOLFIRI. Application of this machine learning approach could lead to improvements in treatment outcomes for patients with CRC and other cancers after additional appropriate clinical validation.
What is moving where? Infants’ visual attention to dynamic objects may assist with processing of spatial relations
Authors: Choi Jihye , Park Youjeong 
Published: January 2024

IntroductionA central question in infant spatial cognition concerns how infants form abstract categories of spatial relations such as support (on) and containment (in). Prior work suggests two different possibilities regarding the role of attention to objects in infants’ formation of abstract categories of spatial relations: Attention to objects may compete with (and thus hamper) attention to the spatial relations between them, or assist with encoding of the spatial relation information. Using eye-tracking, we examined how infants’ visual attention to objects related to their successful formation of an abstract category of support relations (i.e., an object on another).MethodsThirty-eight 8-month-old infants’ eye movements were recorded during a support categorization task, where infants were habituated to four dynamic events depicting support relations (e.g., resting a block on a box) and then presented with test events that depicted either a support or containment relation with objects that they had seen or not seen in the habituation phase. Based on their looking time to the familiar versus novel spatial relation in the test, infants were classified into two groups: categorizers, who formed an abstract category of a support relation, and non-categorizers, who did not do so.ResultsDuring their initial phase of learning (i.e., the first habituation trial), categorizers paid greater attention to the object moved by a hand (i.e., the dynamic object) in comparison to non-categorizers, whereas their attention to the static object or their gaze shifts between the two objects did not differ. In addition, when presented with novel objects in a novel spatial relation after habituation, only categorizers displayed asymmetric attention between the objects, attending to the dynamic object more than the static object. Gaze shifts and attention to the concave area (i.e., hole) of the container did not differ between categorizers and non-categorizers.DiscussionThese findings suggest that infants’ focused attention to an object in motion may play a key role in young infants’ spatial category learning, and support the idea that attention to objects can assist with encoding of the spatial relational information.
A critical analysis of gender-based violence reporting and evidence building applications (GBVxTech) for capturing memory reports
Authors: Stevens Laura M. , Bennett Tia C. , Cotton Jessica , Rockowitz Sarah , Flowe Heather D. 
Published: January 2024

IntroductionGender-based violence (GBV) is under-reported to the authorities owing to the stigma, shame, and fear of reprisal that surrounds these crimes. To address this, there has been an influx of technologies, including mobile phone and online applications that allow victim-survivors (hereafter, victims) to document and report GBV (hereafter referred to as GBVxTech). We critically analysed the extent to which GBVxTech applications align with the scientific knowledge base on gathering accounts of crimes from victims and witnesses.MethodsWe identified 41 reporting and evidence building applications from around the world but found many (n = 19) were no longer accessible. A total of 13 applications met the study criteria and were available for download. We evaluated each application on how well its design and features align with established minimum best practice standards for gathering complete and accurate accounts from witnesses and victims, such as the pre-interview instructions (e.g., setting ground rules), questioning approach (e.g., using open-ended questions), and the adequacy of security features (e.g., password protection).Results and DiscussionWe found most applications employ open questions, encourage victims to report information in an independent voice, and seek to elicit information pertinent to a criminal investigation. None of the applications use leading questions. However, most applications do not establish ground rules, and many use forced-choice questions, do not time stamp the information gathered, or document when users change their answers. Many applications have limited security features, potentially compromising users’ safety. Further, some applications do not provide information about how to use the app, an informed consent procedure, or data usage information. We discuss the findings and offer recommendations for future GBVxTech development.
Pediatric polysomnography-flagging etiologies and impact on the clinical timeline
Authors: Rani Seema , Schanz John , Chauhan Kapil , Kolb August , Gatta Victoria , Strang Abigail , Chidekel Aaron C. 
Published: January 2024

Background/objectiveThere is a paucity of literature regarding “flagging” abnormal sleep studies for expedited review. This single-center retrospective analysis (n = 266) of flagged polysomnography studies from 2019 to 2022 aimed to investigate flagging and its impact on the clinical timeline.MethodsTwo hundred sixty-six flagged polysomnography studies from 2019 to 2022 were retrospectively reviewed.ResultsFlagged study etiologies included repetitive brief oxygen desaturations (46.6%), sustained desaturations (32.3%), sustained hypercapnia (5.6%), or other concerning events (15.5%). The median time between a flagged study and scoring report finalization, medical intervention, and surgical intervention were 0 (2) days, 2 (3) days, 5 (11.25) days, and 44 (73) days, respectively. Patients with apnea–hypopnea index &gt;30 had less time between a flagged study and surgical intervention (65.3 ± 96.7 days vs. 112 ± 119 days, p = 0.044).ConclusionAs anticipated, the time to surgical intervention was longer than to medical intervention. Patients with a higher disease severity experienced quicker scoring, report finalization, and surgical intervention.
Morphological and Phylogenetic Analyses Reveal Three New Species of Didymella (Didymellaceae, Pleosporales) from Jiangxi, China
Authors: Luo Xingxing , Hu Yafen , Xia Jiwen , Zhang Kai , Ma Liguo , Xu Zhaohuan , Ma Jian 
Published: January 2024

Didymella contains numerous plant pathogenic and saprobic species associated with a wide range of hosts. Over the course of our mycological surveys of plant pathogens from terrestrial plants in Jiangxi Province, China, eight strains isolated from diseased leaves of four host genera represented three new species of Didymella, D. bischofiae sp. nov., D. clerodendri sp. nov., and D. pittospori sp. nov. Phylogenetic analyses of combined ITS, LSU, RPB2, and TUB2 sequence data, using maximum-likelihood (ML) and Bayesian inference (BI), revealed their taxonomic placement within Didymella. Both morphological examinations and molecular phylogenetic analyses supported D. bischofiae, D. clerodendri, and D. pittospori as three new taxa within Didymella. Illustrations and descriptions of these three taxa were provided, along with comparisons with closely related taxa in the genus.
Polymorphisms of APOE and APOB genes and dyslipidemias in a South Brazilian Cohort
Authors: Cardozo Gasparin Caroline , Viater Tureck Luciane , Pereira Ferrari Lilian , Lehtonen Rodrigues de Souza Ricardo , Furtado Alle Lupe 
Published: January 2024

Dyslipidemias are closely associated to the development of cardiovascular and cerebrovascular diseases, and therefore of great importance in public health. Many genes influence lipid levels, such as APOE and APOB. The present study aimed to investigate the effects of APOE gene alleles (rs7412: C>T and rs429358: T>C), and R3500Q mutation of APOB gene (rs5742904: G>A) in lipid levels in a South Brazilian cohort. 214 individuals were analyzed and the frequencies of APOE ε2, ε3 and ε4 alleles were found respectively as 9.25 ± 0.4625; 70.5 ± 3.525 and 20.25%± 1.401, while the frequency of R3500Q mutation of the APOB gene was 4.46 ± 1.00%. The ε4 allele was significantly more frequent in subjects with higher TC (Total Cholesterol) and LDL-C levels, while significantly higher frequency of the ε2 allele was found in individuals with higher HDL-C levels. The R3500Q mutation was suggested as a risk factor for higher TC levels, regardless gender and age (β = 21.326 ± 10377.78, p = 0.001).