bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and medical costs of lupus in Spanish hospitals: a retrospective database analysis
Authors: Darba Josep , Ascanio Meritxell , Agüera Ainoa 
Published: February 2024

Abstract
Background
This study aimed to assess the comorbidity profile, use of healthcare resources and medical costs of patients with systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) treated at the hospital level in Spain.

Methods
Admission records of patients with SLE and CLE that were registered between January 2016 and December 2020 were obtained from a Spanish hospital discharge database and analyzed in a retrospective multicenter study.

Results
329 patients met the criteria; 64.44% were female and 35.56% were male, with a median age of 54.65 years. Mean Charlson comorbidity index (CCI) was 2.75 in the index admission. 31.61% of the patients suffered essential hypertension, 21.96% suffered asthma and 19.76% suffered hyperlipidemia. Mortality rate was 3.95%. The most common medical procedure was heart ultrasound (19.45%) and introduction in peripheral vein of anti-inflammatory with a percutaneous approach (17.93%). Mean admission cost was €6355.99.

Conclusions
Lupus patients showed a higher incidence and prevalence in the female population, with associated cardiac diseases as the main secondary conditions.
The synergism of SMC1A cohesin gene silencing and bevacizumab against colorectal cancer
Authors: Di Nardo Maddalena , Astigiano Simonetta , Baldari Silvia , Pallotta Maria Michela , Porta Giovanni , Pigozzi Simona , Antonini Annalisa , Emionite Laura , Frattini Annalisa , Valli Roberto , Toietta Gabriele , Soddu Silvia , Musio Antonio 
Published: February 2024

Abstract
Background
SMC1A is a subunit of the cohesin complex that participates in many DNA- and chromosome-related biological processes. Previous studies have established that SMC1A is involved in cancer development and in particular, is overexpressed in chromosomally unstable human colorectal cancer (CRC). This study aimed to investigate whether SMC1A could serve as a therapeutic target for CRC.

Methods
At first, we studied the effects of either SMC1A overexpression or knockdown in vitro. Next, the outcome of SMC1A knocking down (alone or in combination with bevacizumab, a monoclonal antibody against vascular endothelial growth factor) was analyzed in vivo.

Results
We found that SMC1A knockdown affects cell proliferation and reduces the ability to grow in anchorage-independent manner. Next, we demonstrated that the silencing of SMC1A and the combo treatment were effective in increasing overall survival in a xenograft mouse model. Functional analyses indicated that both treatments lead to atypical mitotic figures and gene expression dysregulation. Differentially expressed genes were implicated in several pathways including gene transcription regulation, cellular proliferation, and other transformation-associated processes.

Conclusions
These results indicate that SMC1A silencing, in combination with bevacizumab, can represent a promising therapeutic strategy for human CRC.
Recurrent upper respiratory tract infections in early childhood: a newly defined clinical condition
Authors: Corsello Antonio , Milani Gregorio Paolo , Picca Marina , Buzzetti Roberto , Carrozzo Romeo , Gambino Mirko , Chiaffoni Giovanni , Marchisio Paola , Mameli Chiara 
Published: February 2024

Abstract
Background
Recurrent Upper Respiratory Tract Infections (R-URTIs) pose a significant challenge in pediatric healthcare, affecting both children and their families. This study aimed to investigate the prevalence, risk factors, and clinical implications of R-URTI in children aged 0–5 years.

Methods
This observational study involved a sample of 483 children aged 0–5 years, focusing on establishing a practical and dynamic definition of R-URTI. Family pediatricians prospectively collected socio-demographic information, medical history, and recorded the occurrence of URTI episodes. Children were followed from recruitment until March 2021, predating the COVID-19 outbreak.

Results
A substantial prevalence of R-URTIs was found, estimating it at 5–10% among this age group. To define R-URTI, a practical and dynamic criterion was proposed: children experiencing a minimum of four URTI episodes, each lasting four days or more, within a six-month period, with intervals of well-being in between.

Conclusions
The study highlighted that specific risk factors for R-URTI were elusive, suggesting that this condition may affect children regardless of their family or clinical history. Moreover, the study’s stratification by age group and times of observation facilitated patient-specific clinical decision-making. The proposed definition may represent a valuable tool for clinicians in diagnosing and addressing R-URTI cases.
Using a theory-based, customized video game as an educational tool to improve physicians’ trauma triage decisions: study protocol for a randomized cluster trial
Authors: Mohan Deepika , Angus Derek C. , Chang Chung-Chou H. , Elmer Jonathan , Fischhoff Baruch , Rak Kim J. , Barnes Jacqueline L. , Peitzman Andrew B. , White Douglas B. 
Published: February 2024

Abstract
Background
Transfer of severely injured patients to trauma centers, either directly from the field or after evaluation at non-trauma centers, reduces preventable morbidity and mortality. Failure to transfer these patients appropriately (i.e., under-triage) remains common, and occurs in part because physicians at non-trauma centers make diagnostic errors when evaluating the severity of patients’ injuries. We developed Night Shift, a theory-based adventure video game, to recalibrate physician heuristics (intuitive judgments) in trauma triage and established its efficacy in the laboratory. We plan a type 1 hybrid effectiveness-implementation trial to determine whether the game changes physician triage decisions in real-life and hypothesize that it will reduce the proportion of patients under-triaged.

Methods
We will recruit 800 physicians who work in the emergency departments (EDs) of non-trauma centers in the US and will randomize them to the game (intervention) or to usual education and training (control). We will ask those in the intervention group to play Night Shift for 2 h within 2 weeks of enrollment and again for 20 min at quarterly intervals. Those in the control group will receive only usual education (i.e., nothing supplemental). We will then assess physicians’ triage practices for older, severely injured adults in the 1-year following enrollment, using Medicare claims, and will compare under-triage (primary outcome), 30-day mortality and re-admissions, functional independence, and over-triage between the two groups. We will evaluate contextual factors influencing reach, adoption, implementation, and maintenance with interviews of a subset of trial participants (n = 20) and of other key decision makers (e.g., patients, first responders, administrators [n = 100]).

Discussion
The results of the trial will inform future efforts to improve the implementation of clinical practice guidelines in trauma triage and will provide deeper understanding of effective strategies to reduce diagnostic errors during time-sensitive decision making.

Trial registration
ClinicalTrials.gov; NCT06063434. Registered 26 September 2023.
Regulatory T and B cells in pediatric Henoch–Schönlein purpura: friends or foes?
Authors: Filleron Anne , Cezar Renaud , Fila Marc , Protsenko Nastassja , Van Den Hende Kathleen , Jeziorski Eric , Occean Bob , Chevallier Thierry , Corbeau Pierre , Tran Tu Anh 
Published: February 2024

Abstract
Background and objectives
Henoch–Schönlein purpura (HSP) is the most common immunoglobulin A-mediated systemic vasculitis in childhood. We studied immune dysregulation in HSP by analyzing regulatory T (Treg), T helper 3 (Th3), and regulatory B cell (Breg) subpopulations that might intervene in immune activation, IgA production, and HSP clinical manifestations.

Methods
This prospective study included 3 groups of children: 30 HSP on acute phase, 30 HSP on remission, and 40 healthy controls (HCs) matched on age. Treg, Breg, and Th3 were analyzed by flow cytometry. Serum immunoglobulin and cytokine levels were quantified by ELISA and Luminex.

Results
Treg frequencies were higher in acute HSP than in remitting HSP and HCs (6.53% [4.24; 9.21] vs. 4.33% [3.6; 5.66], p = 0.002, and vs. 4.45% [3.01; 6.6], p = 0.003, respectively). Activated Th3 cells (FoxP3 + Th3 cells) tend to be more abundant in HSP than in HCs (78.43% [50.62; 80.84] vs. 43.30% [40.20; 49.32], p = 0.135). Serum IgA, IL-17, and latency-associated peptide (a marker of the anti-inflammatory cytokine TGF-beta production) were significantly and inflammatory cytokines TNF-alpha, IL-1-beta, and IL-6 were non-significantly higher in HSP than HCs. Bregs were identical between the groups, but, in patients with renal impairment, Breg percentage was lower compared to those without. Treg removal in PBMC culture resulted in an increase in IgA production in HSP proving a negative regulatory role of Tregs on IgA production.

Conclusions
In pediatric HSP, immune activation persists in spite of an increase in Th3 and Tregs. Th3 could be involved in IgA hyperproduction, inefficiently downregulated by Tregs. Lack of Bregs appears linked to renal impairment.
SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway
Authors: Zeng Xiao-chun , Tian Yuan , Liang Xian-ming , Wu Xiao-bin , Yao Chun-meng , Chen Xiao-min 
Published: February 2024

Abstract
Aims
To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients.

Materials and methods
68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30 mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300 mg/g), T2DM with macroalbuminuria group (UACR>300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels.

Results
After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), the reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of 24-h proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r = −0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients.

Conclusions
SGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal oxidative stress, but not through the AGEs pathway and does not induce RAAS activation.

Trial registration
This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.
Genome-wide association study and polygenic risk scores of retinal thickness across the cognitive continuum: data from the NORFACE cohort
Authors: Sáez María Eugenia , García-Sánchez Ainhoa , de Rojas Itziar , Alarcón-Martín Emilio , Martínez Joan , Cano Amanda , García-González Pablo , Puerta Raquel , Olivé Clàudia , Capdevila Maria , García-Gutiérrez Fernando , Castilla-Martí Miguel , Castilla-Martí Luis , Espinosa Ana , Alegret Montserrat , Ricciardi Mario , Pytel Vanesa , Valero Sergi , Tárraga Lluís , Boada Mercè , Ruiz Agustín , Marquié Marta 
Published: February 2024

Abstract
Background
Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer’s disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness.

Methods
RNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated.

Results
Several genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered.

Conclusions
Our study does not support the existence of a genetic link between dementia and retinal thickness.
The search for clarity regarding “clinically meaningful outcomes” in Alzheimer disease clinical trials: CLARITY-AD and Beyond
Authors: Tarawneh Rawan , Pankratz Vernon S. 
Published: February 2024

AbstractCLARITY-AD is an 18-month, double-blinded, placebo-controlled, phase 3 trial which examined the safety and efficacy of the anti-amyloid agent, lecanemab, in mild cognitive impairment and mild dementia due to Alzheimer disease (AD). Lecanemab effectively reduced mean brain amyloid burden and was associated with statistically significant favorable effects, reflected by moderately less decline in the primary and secondary clinical outcomes, at 18 months compared to placebo. However, there is controversy within the AD community regarding the clinical significance of these results and whether they translate into clinically meaningful and tangible benefits on cognition or daily functions.We here review the primary and secondary clinical outcomes of CLARITY-AD and present our interpretation of the potential clinical meaningfulness of the group-level differences in study outcomes in the context of the 18-month study duration. We propose that the validation of stage-appropriate group-level thresholds for clinical meaningfulness of AD trial outcomes in biologically confirmed cohorts will allow objective interpretation of trial results and guide clinical decision-making. Further, in accordance with FDA guidance which emphasizes patient-focused drug development, the contextualization of AD clinical trial outcomes can be facilitated by supplementary individual-level data analyses which measure the risk of disease progression or summarize intraindividual change, using prespecified thresholds of clinically meaningful change, in each of the study groups over the trial period. The concepts of “time-saved” and “time-based” slowing in disease progression can be used to communicate clinical outcomes associated with emerging disease-modifying AD therapies to various stakeholders. We also describe several factors that need to be considered when evaluating outcomes of emerging AD therapies, including disease stage, the neuropathologic complexity of AD, time-based effects of disease-modifying therapies, and the possible influence of individual factors on treatment response and/or risk for adverse events. The consideration of these factors in the design and reporting of future trials of emerging AD therapies will guide clinicians regarding their appropriateness for use in various patient populations.Finally, we emphasize that data from clinical cohorts with longer durations of treatment and follow-up, including extension studies and patient registries, is needed to evaluate the long-term safety and efficacy of lecanemab in early symptomatic AD.
Intravoxel incoherent motion diffusion-weighted imaging for predicting kidney allograft function decline: comparison with clinical parameters
Authors: Wang Wei , Yu Yuanmeng , Chen Jinsong , Zhang Longjiang , Li Xue 
Published: February 2024

Abstract
Objective
To evaluate the added benefit of diffusion-weighted imaging (DWI) over clinical parameters in predicting kidney allograft function decline.

Methods
Data from 97 patients with DWI of the kidney allograft were retrospectively analyzed. The DWI signals were analyzed with both the mono-exponential and bi-exponential models, yielding total apparent diffusion coefficient (ADCT), true diffusion (D), pseudo-diffusion (D*), and perfusion fraction (fp). Three predictive models were constructed: Model 1 with clinical parameters, Model 2 with DWI parameters, and Model 3 with both clinical and DWI parameters. The predictive capability of each model was compared by calculating the area under the receiver-operating characteristic curve (AUROC).

Results
Forty-five patients experienced kidney allograft function decline during a median follow-up of 98 months. The AUROC for Model 1 gradually decreased with follow-up time > 40 months, whereas Model 2 and Model 3 maintained relatively stable AUROCs. The AUROCs of Model 1 and Model 2 were not statistically significant. Multivariable analysis showed that the Model 3 included cortical D (HR = 3.93, p = 0.001) and cortical fp (HR = 2.85, p = 0.006), in addition to baseline estimated glomerular filtration rate (eGFR) and proteinuria. The AUROCs for Model 3 were significantly higher than those for Model 1 at 60-month (0.91 vs 0.86, p = 0.02) and 84-month (0.90 vs 0.83, p = 0.007) follow-up.

Conclusions
DWI parameters were comparable to clinical parameters in predicting kidney allograft function decline. Integrating cortical D and fp into the clinical model with baseline eGFR and proteinuria may add prognostic value for long-term allograft function decline.

Critical relevance statement
Our findings suggested that cortical D and fp derived from IVIM-DWI increased the performance to predict long-term kidney allograft function decline. This preliminary study provided basis for the utility of multi-b DWI for managing patients with a kidney transplant.

Key points
• Both clinical and multi-b DWI parameters could predict kidney allograft function decline.
• The ability to predict kidney allograft function decline was similar between DWI and clinical parameters.
• Cortical D and fp derived from IVIM-DWI increased the performance to predict long-term kidney allograft function decline.

Graphical Abstract
Imaging-based deep learning in kidney diseases: recent progress and future prospects
Authors: Zhang Meng , Ye Zheng , Yuan Enyu , Lv Xinyang , Zhang Yiteng , Tan Yuqi , Xia Chunchao , Tang Jing , Huang Jin , Li Zhenlin 
Published: February 2024

AbstractKidney diseases result from various causes, which can generally be divided into neoplastic and non-neoplastic diseases. Deep learning based on medical imaging is an established methodology for further data mining and an evolving field of expertise, which provides the possibility for precise management of kidney diseases. Recently, imaging-based deep learning has been widely applied to many clinical scenarios of kidney diseases including organ segmentation, lesion detection, differential diagnosis, surgical planning, and prognosis prediction, which can provide support for disease diagnosis and management. In this review, we will introduce the basic methodology of imaging-based deep learning and its recent clinical applications in neoplastic and non-neoplastic kidney diseases. Additionally, we further discuss its current challenges and future prospects and conclude that achieving data balance, addressing heterogeneity, and managing data size remain challenges for imaging-based deep learning. Meanwhile, the interpretability of algorithms, ethical risks, and barriers of bias assessment are also issues that require consideration in future development. We hope to provide urologists, nephrologists, and radiologists with clear ideas about imaging-based deep learning and reveal its great potential in clinical practice.Critical relevance statement The wide clinical applications of imaging-based deep learning in kidney diseases can help doctors to diagnose, treat, and manage patients with neoplastic or non-neoplastic renal diseases.Key points• Imaging-based deep learning is widely applied to neoplastic and non-neoplastic renal diseases.• Imaging-based deep learning improves the accuracy of the delineation, diagnosis, and evaluation of kidney diseases.• The small dataset, various lesion sizes, and so on are still challenges for deep learning.
Graphical Abstract
Bruns Garland Syndrome as the first presentation of type 2 diabetes: two case reports and a practical approach to diagnosis
Authors: Ambawatte Sathyajith , Wijewickrama Piyumi , Gunarathne Kamal , Somasundaram Noel 
Published: February 2024

Abstract
Background
Diabetes is a global health problem causing a significant burden on the healthcare systems both due to the disease itself and associated complications. Diabetic radiculoplexus neuropathies or Bruns–Garland syndrome constitutes a rare form of microvascular complications, more commonly affecting the lumbosacral plexus and, very rarely, the cervical plexus. We describe two Sri Lankan males who presented with diabetic lumbosacral radiculoplexus neuropathy and diabetic cervical radiculoplexus neuropathy as the initial manifestation of diabetes.

Case description
Case 1: a 49-year-old Sri Lankan hotel chef presented with subacute painful weakness and wasting of the left upper arm for 3 months and weight loss. Left upper limb proximal muscles were wasted with diminished power and reflexes. A nerve conduction study showed comparative amplitude reduction. An electromyogram revealed positive sharp waves, frequent fibrillations, and high amplitude polyphasic motor unit potentials with reduced recruitment in proximal muscles of left upper limb. Case-2: a 47-year-old Sri Lankan carpenter presented with subacute progressive asymmetrical painful weakness and wasting of bilateral thighs for 5 months and weight loss. Lower limb proximal muscles were wasted with reduced power and knee jerks. The nerve conduction study was normal. The electromyogram was similar to case 1 involving both quadratus femoris muscles, which was more prominent on the left side. The work up for an underlying etiology revealed only elevated fasting blood glucose and HbA1c, suggesting a new diagnosis of diabetes associated with neurological symptoms. Patient 1 was diagnosed with diabetic cervical radiculoplexus neuropathy and patient 2 with diabetic lumbosacral radiculoplexus neuropathy. Both showed significant improvement following optimization of glycemic control together with symptomatic treatment and physiotherapy.

Conclusion
Diagnosis of diabetic radiculoplexus neuropathy requires a comprehensive workup to rule out other sinister pathologies. This case report has a dual importance; it describes diabetic radiculoplexus neuropathy as the very first manifestation of two previously healthy people, giving rise to a new diagnosis of diabetes and, at the same time, reporting on diabetic cervical radiculoplexus neuropathy, which is extremely rare and has never been previously reported in Sri Lanka.