bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial fibrillation screening in Syrian patients reporting to the emergency department during the ongoing conflict: a cross-sectional study
Authors: Antoun Ibrahim , Alkhayer Alkassem , Jalal Eldin Aref , Alkhayer Alamer , Salama Ibrahim , Yazji Khaled , Somani Riyaz , Ng G. André , Zakkar Mustafa
Published: February 2025

Background

Atrial fibrillation (AF) is the most common arrhythmia worldwide. Data regarding AF screening in conflict countries’ emergency departments (ED) is lacking.

Methods

We included consecutive patients >40 years old who reported to the ED of a Syrian tertiary centre between July 2024 and September 2024. Patients had routine 12-lead electrocardiograms (ECGs) regardless of presenting complaints. Two cardiology consultants blindly verified ECG findings. We excluded critically unwell patients and ECG discrepancies between the two consultants. Data were taken from patients’ medical notes.

Results

The final analysis included 694 patients, 101 (15%) had AF on the ECG. The most common presenting complaints and ECG abnormality were trauma (44%) and sinus tachycardia (15%), respectively. Compared to the rest of the patients, AF patients were older (66 vs. 59 years; p < 0.001), had a lower proportion of males (39% vs. 54%; p = 0.01), a higher prevalence of diabetes mellitus (49% vs. 21%; p = 0.01), and more cases of congestive cardiac failure (CCF) (38% vs. 17%; p < 0.001). AF patients also had a higher CHA₂DS₂-VASc score (3 vs. 2; p < 0.001). CCF [odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.5–6.4, p < 0.001] and a higher CHA₂DS₂-VASc score(OR: 4, 95% CI: 1.6–7.7, p < 0.001) were independently associated with positive AF screening.

Conclusion

15% of patients reporting to this Syrian ED had positive AF screening. CCF and CHA₂DS₂-VASc scores are predictive of AF.
Antiplatelet strategy for patients with acute coronary syndrome and chronic kidney disease: a systematic review and meta-analysis
Authors: Li Siqi , Wang Dayang , Han Xiaowan , Zhang Diying , Deng Hongxiao , Pan Guozhong
Published: February 2025

Background

Patients with both acute coronary syndrome (ACS) and chronic kidney disease (CKD) face heightened risks of adverse cardiovascular events and bleeding. An optimal antiplatelet strategy for this patient population is needed.

Methods

We conducted a systematic review and meta-analysis to evaluate comparative advantages of clopidogrel vs. ticagrelor in the choice of dual antiplatelet therapy (DAPT) strategies for patients with ACS combined with CKD, while also exploring the appropriate duration of DAPT in the presence of CKD. Relevant studies were retrieved from PubMed, Embase, Cochrane Library, and Web of Science. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE), and major bleeding. Data were analyzed using RevMan 5.4.1, and STATA 14 was used to assess publication bias. This study was registered with PROSPERO (CRD42024593764).

Results

Six studies involving 9,947 patients met the inclusion criteria. Compared with clopidogrel, ticagrelor was associated with a reduced risk of MACE (RR: 0.89, 95% CI: 0.80–0.99; P = 0.04) and stroke (RR: 0.66, 95% CI: 0.45–0.96; P = 0.03) in patients receiving DAPT. No significant differences were observed in all-cause mortality, major bleeding, cardiovascular death, or acute myocardial infarction. Three studies on DAPT duration showed a consistent trend, indicating that shortening DAPT duration did not benefit patients.

Conclusions

In patients with ACS combined with CKD, ticagrelor-based DAPT has advantages over clopidogrel-based DAPT, which is associated with a lower incidence of MACE. And shortening the duration of DAPT does not improve clinical outcomes.
Five-year evaluation of bone health in liver transplant patients: developing a risk score for predicting bone fragility progression beyond the first year
Authors: Abate Ejigayehu G. , McKenna Amanda , Yang Liu , Ball Colleen T. , Kearns Ann E.
Published: February 2025

Introduction

Liver transplant (LT) recipients have a substantial risk of bone loss and fracture. An individual’s risk is highest before and within the first year after transplantation and returns to baseline in some patients but not all. We aim to identify risk factors for bone loss and fracture beyond the first year LT and to create a risk-scoring tool to aid clinicians in identifying those at high risk for bone loss and fracture.

Methods

We conducted a retrospective review of 264 liver transplant recipients between 2011 and 2014, who were followed in our transplant clinic for an additional five years. Clinical records were evaluated at the one-year post-LT visit and subsequently on an annual basis for up to five years.

Results

Over a median follow-up of 3.6 years post-liver transplantation, 40 out of 264 patients experienced disease progression, defined as worsening bone mineral density (BMD), initiation of osteoporosis treatment, or a new fracture. Factors associated with BMD progression included female sex, Caucasian race, new fractures, number of acute rejection events requiring treatment, and lower dual energy X-ray absorptiometry (DXA) scores after the first year post-LT. A risk model was developed using multivariable analysis, with a risk score based on BMD categories. The concordance index was 0.771, indicating good discrimination between those who progressed and those who did not. Risk categories were defined as low (0-4 points), medium (5 points), and high (6-9 points) based on model coefficients. The probability of progression-free survival at two years post-LT was 96.7% for low-risk, 83.1% for medium-risk, and 59.1% for high-risk groups.

Conclusion

We developed a simple, clinically applicable risk score that predicts bone disease progression beyond the first year after LT. This tool may help guide appropriate bone health follow-up, although prospective validation is necessary.
Ultrasound speckle tracking imaging measurement of endocardial longitudinal strain for evaluation of prognostic value of “new quadruple” therapy in patients with chronic heart failure
Authors: Tang Man , Zeng Yuwei , Zhao Ping , Zhao Qianlei
Published: February 2025

Purpose

This study aimed to evaluate the effectiveness of the “new quadruple” therapy in chronic heart failure (CHF) patients with metabolic syndrome using 2D speckle tracking imaging (2D-STI) stratified strain imaging to measure endocardial longitudinal strain while exploring its underlying neuroendocrine mechanisms.

Patients and methods

The study retrospectively analyzed 158 patients with heart failure with reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) < 40%] treated with the “new quadruple” therapy (angiotensin receptor neprilysin inhibitor (ARNI), sacubitril/valsartan, dapagliflozin, bisoprolol, and spironolactone) for 8 weeks. Conventional ultrasound indices, left ventricular global longitudinal strain (LVGLS), and subendocardial longitudinal strain (LS) were measured pre- and post-treatment. Follow-up for 15 months recorded major adverse cardiac events (MACEs).

Results

The 158 patients were divided into two groups: MACEs (n=25) and no MACEs (n=133). Univariate comparisons revealed significant differences between groups in coronary artery diameter stenosis percentage; admission LVEF and brain natriuretic peptide (BNP); LVGLS and subendocardial LS; post-treatment LVEF, LVGLS, and subendocardial LS, ΔLVGLS; and subendocardial ΔLS (P < 0.05). Multifactorial Cox regression modeling showed that coronary artery diameter stenosis, admission LVEF, BNP, subendocardial LS, post-treatment LVEF, and subendocardial LS were predictive factors for MACEs in HFrEF patients following “new quadruple” therapy (P < 0.05). ROC analysis indicates that post-treatment subendocardial LS predicts MACEs with an AUC of 0.871, which was significantly higher than other single metrics (P < 0.05).

Conclusions

Using 2D-STI layer-specific strain imaging to measure endocardial longitudinal strain serves as a significant non-invasive indicator in predicting MACEs during 1-year follow-up after “new quadruple” therapy in HFrEF patients with metabolic syndrome, highlighting substantial clinical applicability. Additionally, our findings suggest that the therapy may improve prognosis through the modulation of neuroendocrine mechanisms.
Unlocking the fog: assessing fog collection potential and need as a complementary water resource in arid urban lands–the Alto Hospicio, Chile case
Authors: Carter Virginia , Verbrugghe Nathalie , Lobos-Roco Felipe , del Río Camilo , Albornoz Francisco , Khan Ahmed Z.
Published: February 2025

Water scarcity is a rising issue in fast-growing cities in arid lands, where demand outpaces supply. This leads to non-renewable water systems and exacerbates social inequalities. This is the case for Alto Hospicio (AH), located in the northern Chilean Atacama Desert. Regarding its water availability, the main source of drinking water comes from underground aquifers, last recharged about 10,000 years ago. Nevertheless, atmospheric water such as fog, is present in this territory and offers an alternative, though its potential in large urban areas remains unexplored. This study assesses the fog water collection potential in AH and its surroundings using two methods: in-situ data collection using Standard Fog Collectors (SFCs) and the AMARU model, which estimates fog collection in space and time. This research concludes that fog water collection is feasible in the northeast and southeast areas surrounding the city, where fog collection rates reach up to 10 L m−2 day−1. Fog water has the potential to serve as an effective alternative water source for populations lacking access to drinking water from a public water source, and for activities such as irrigation of urban green spaces, human consumption, and hydroponic farming. Key recommendations for policymakers include incorporating atmospheric water into local city policies, promoting further research on estimating the fog water potential in the AH metropolitan zone, and rethinking water management strategies from nonconventional resources.
Multiscale impacts of landscape metrics on water quality based on fine-grained land use maps
Authors: Zhou Ya’nan , He Jinke , Feng Li , Wang Binyao , Chen Yuehong , Miao Lingzhan
Published: February 2025

Quantifying the impact of landscape metrics on water quality can offer scientific supports for water conservation and land use planning. However, previous studies mainly relied on coarse land use maps, and were lack of understanding of effects from physiographic metrics. Here, based on the in-situ water quality monitoring data in the Fujiang river basin, we used redundancy analysis, variation partitioning analysis, and Shapley Additive exPlanations methods to assess the impact of landscape metrics on water quality. We use these analyses in the dry and wet season, in circular buffer zone, in riparian buffer zone, and at the sub-basin scale, we are able to analyze and understand the complex interactions between landscape features and water quality, as well as spatial and temporal scale effects. The results indicated that the impact of landscape metrics on water quality variation can be ranked in the following order: landscape composition (15.8%–32.2%) > landscape configuration (1.2%–19.5%)> physiographic metrics (−2.0%-0.6%). Forests and grasslands improved water quality, whereas farmland and impervious surfaces degraded water quality. At a finer scale of land use types, closed broadleaf evergreen forests improved water quality, while rainfed cropland had the opposite effect. The 1500 m circular buffer was the key scale with the highest rate of interpretation. The relationship between landscape metrics and water quality was marginally stronger during the wet season than the dry season. Water quality was improved by large relief amplitude and slope standard deviation. The water quality is not significantly affected by the river network density, the length of the river, or the basin area. These conclusions could provide science-informed information and support to the study between landscape metrics and water quality.
Instability and uncertainty of carbon storage in karst regions under land use change: a case study in Guiyang, China
Authors: Zhou Heng , Tang Mingdong , Huang Jun , Zhang Jinting , Huang Jingnan , Zhao Haijuan , Yu Yize
Published: February 2025

Introduction

Karst regions are integral to the global carbon cycle. However, land use changes of karst regions driven by urbanization and desertification contribute to the instability of carbon storage, leading to uncertainties in the future. Understanding these instabilities and uncertainties is crucial for formulating carbon sequestration and land management strategies.

Methods

This study employed Patch-generating Land Use Simulation (PLUS) and Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) to estimate carbon storage, and introduced the Coefficient of Variation (CV) to assess the instability and uncertainty. Multiscale Geographically Weighted Regression (MGWR) was applied to explore the mechanisms, while Polynomial Regression (PR) identified the stable intervals of factors, informing land-use policies.

Results and Discussion

(1) From 2000 to 2020, Guiyang’s carbon storage rose from 136.62 Tg to 142.13 Tg. By 2035, projections under natural development, urban expansion, and ecological protection scenarios estimate increases to 147.50 Tg, 147.40 Tg, and 147.82 Tg, respectively. (2) Carbon storage instability increased from 2000 to 2020, while uncertainty is expected to decrease by 2035. Instability was primarily due to transitions of Cropland-Forest, Forest-Cropland, Cropland-Grassland, and Cropland-Impervious, while uncertainties mainly arise from Cropland-Forest, Cropland-Impervious, and Grassland-Impervious transitions. (3) DEM, AI, Distance from national highways, SHDI, and Mean annual precipitation affected instability significantly. (4) Encouraging Shrub-Forest, Shrub-Cropland and Cropland-Forest conversions, and controlling Forest-Cropland, Forest-Shrub, and Cropland-Impervious conversions within the stable intervals of factors, can enhance carbon storage and reduce uncertainty. This study establishes a methodology for evaluating carbon storage instability and uncertainty in karst regions, which is an extension of carbon storage research.
Comprehensive systematic review and meta-analysis of the TGF-β1 T869C gene polymorphism and autoimmune disease susceptibility
Authors: Zhu Yawen , Qian Ai , Cheng Yuanyuan , Li Ming , Huang Chuanbing
Published: February 2025

Objective

Autoimmune diseases (ADs) result from an aberrant immune response, in which the body mistakenly targets its own tissues. The association between TGF-β1 gene polymorphisms and risk of developing autoimmune diseases remains to be established. This meta-analysis aimed to reassess the relationship between TGF-β1 T869C gene polymorphisms and susceptibility to autoimmune diseases.

Methods

We conducted a comprehensive search of seven electronic databases for case-control studies investigating the TGF-β1 T869C polymorphism in relation to autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and juvenile idiopathic arthritis. The search encompassed publications published up to June 2024. Studies were categorized by ethnicity into three groups: Asian, Caucasian, and mixed-ethnicity groups. Five different genetic models were assessed, and the quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Statistical analyses were performed using Stata 14.0, by calculating the odds ratio (OR) and 95% confidence interval (CI).

Results

A total of 32 case-control studies (31 articles), comprising 4,304 cases and 4,664 controls, were included in this meta-analysis. The overall analysis indicated no significant association between TGF-β1 T869C gene polymorphism and susceptibility to autoimmune diseases. However, subgroup analyses based on race and disease status revealed significant associations. Ethnic subgroup analysis showed that the TGF-β1 T869C allele model (T vs C: OR = 1.422, 95% CI = 1.109–1.824, P = 0.006), homozygous model (TT vs CC: OR = 1.923, 95% CI = 1.232–3.004, P = 0.004), and dominant model (TT + TC vs CC: OR = 1.599, 95% CI = 1.164–2.196, P = 0.004) were associated with autoimmune disease susceptibility in Asians. In the disease subgroup analysis, the results showed that the TGF-β1 T869C allele model (T vs C: OR = 1.468, 95% CI = 1.210–1.781, P = 0.000), recessive model (TT vs TC + CC: OR = 1.418, 95% CI = 1.097–1.832, P = 0.008), dominant model (TT + TC vs CC: OR = 1.747, 95% CI = 1.330–2.295, P = 0.000), homozygous model (TT vs CC: OR = 1.937, 95% CI = 1.373–2.734, P = 0.000), and heterozygous model (TC vs CC: OR = 1.555, 95% CI = 1.199–2.016, P = 0.001) were associated with rheumatoid arthritis susceptibility.

Conclusion

The findings of this meta-analysis suggest that carrying the T allele of the TGF-β1 T869C polymorphism increases the risk of autoimmune diseases in Asian populations. Moreover, individuals carrying the T allele are at higher risk of developing rheumatoid arthritis.
Interaction between nasal epithelial cells and Tregs in allergic rhinitis responses to allergen via CCL1/CCR8
Authors: Sha Jichao , Yang Maolin , Lei Yashu , Sun Liwei , Meng Cuida , Zhu Dongdong
Published: February 2025

Background

The airway epithelial barrier is the first defence against aeroallergens. Nasal epithelial cells (NECs) are vital in regulating innate and adaptive mucosal immunity in allergic rhinitis (AR). Tregs produce cytokines essential for the immunomodulatory activities in allergen immunotherapy. Understanding the relationship between NECs and Tregs in the airway hyperresponsiveness network is essential for developing novel treatments.

Methods

Using an in vitro human Treg-NEC co-culture system of AR and health control group, the chemokine expression profiles of NECs were examined using immunohistochemistry, RT-PCR, and ELISA, and functional surface markers of Tregs were detected using flow cytometric analysis. Correlation analysis was performed between cytokines derived from NECs and surface markers of CD4+CD8+Foxp3+ Tregs in the AR group after co-culture, including TSLP/CTLA4, CCL1/CTLA4, TSLP/CTLA4, TSLP/CCR8, and CCL1/CCR8.

Results

CCR8 and CTLA-4 expressions after co-culturing were higher than single culture. Following Derp1 stimulation, TSLP, IL-25 and TGF-β expressions in the AR + Derp1 group were increased. CCL1 mRNA was lower in the AR + Derp1 group than control group. In the AR + Derp1 group, TSLP was higher, and CCL1 protein levels were decreased. There were no significant differences in IL-25, TGF-β and IL-10. When Treg co-culture group added, changes were similar to that observed in pNECs. After co-culture, CCL1/CCR8 was positively correlated in AR.

Conclusion

Human pNECs can communicate with Tregs directly, CCL1/CCR8 may be the pathway between NECs and Tregs in vitro and may play a key role in the immune network of AR.
Super-resolution of nodal and paranodal disruption in anti-pan-neurofascin-associated autoimmune nodopathy
Authors: da Cruz Neris Geßner Vinicius , Linke Janis Theobald , Peulen Thomas-Otavio , Appeltshauser Luise , Sommer Claudia , Brämer Dirk , Geis Christian , Heinze Katrin Gertrud , Doppler Kathrin
Published: February 2025

Introduction

In autoimmune nodopathies, autoantibodies target the nodes of Ranvier, impairing saltatory nerve conduction. Understanding the impact of autoantibody binding on protein assembly is crucial for gaining insights into the pathogenicity of different autoantibodies. We investigated nodal, paranodal, and cytoskeletal axonal proteins in teased fibers from a sural nerve biopsy of a patient with anti-pan-neurofascin autoantibodies. Conventional diagnostic tools, including fluorescence microscopy, often miss subtle alterations at the ultrastructural level.

Methods

We utilized direct stochastic optical reconstruction microscopy (dSTORM), a super-resolution fluorescence imaging technique, to assess the nanoscale architecture of nodal, paranodal, and cytoskeletal axonal proteins.

Result

While conventional fluorescence microscopy revealed severe paranodal and nodal damage in 14% of the nodes, with 86% appearing normal at first glance, the super-resolved images revealed a decreased neurofascin-155 and Caspr-1 density, but preserved colocalization of these adhesion proteins in paranodes that initially seemed normal. At the nodes, sodium channel density and distribution remained intact, but neurofascin-186 density was reduced. Axonal beta-IV spectrin was altered only in severely damaged nodes. This indicates that axonal integrity is largely preserved, with a potentially reversible decrease in paranodal and nodal adhesion proteins in patients with nodopathy revealing subtle alterations in nodal integrity that are not apparent with conventional imaging.

Discussion

These likely reversible changes may explain the rapid recovery seen in patients with anti-pan-neurofascin autoantibodies following autoantibody depletion. Conversely, the small percentage of severely and axonally damaged nodes may account for the residual symptoms experienced by most patients.
Antibiotic pretreatment inhibits white band disease infection by suppressing the bacterial pathobiome
Authors: Selwyn Jason D. , Despard Brecia A. , Galvan-Dubois Kai A. , Trytten Emily C. , Vollmer Steven V.
Published: February 2025

Diseases have caused unprecedent mortality in Caribbean coral communities. White band disease (WBD) has killed up to 95% of all endangered Caribbean Acroporids since it was first observed in 1979. Despite the devastating impacts of WBD, its etiology is currently unknown although recent research identified two bacterial strains – ASVs classified as a Cysteiniphilum litorale and a Vibrio sp., as the most likely pathogens. To better understand the disease etiology of WBD, we pretreated corals with antibiotics to determine how prophylactic use of antibiotics impacts the transmission of WBD in a replicated tank-based experiment. We found the prophylactic use of antibiotics led to significantly reduced infection rates in disease exposed corals with a 30-percentage point decrease in the infection rate. Analyses of 16S rRNA amplicon gene sequencing data in the disease exposed corals demonstrated that antibiotic pretreatment resulted in coral microbiomes which were less speciose and contained relatively fewer Vibrio spp. than untreated corals, indicating that the benefit of the antibiotic pretreatment was its ability to reduce the relative abundance of intrinsic secondary opportunists and/or opportunistic pathogens suggesting their likely importance to the etiology of WBD. We propose two distinct etiologies involving either an extrinsic keystone pathogen (Cysteiniphilum litorale) or overgrowth of intrinsic opportunistic pathogens (Vibrio spp.). Future research should isolate these strains to confirm the etiology of white band disease.
Breaking new ground: machine learning enhances survival forecasts in hypercapnic respiratory failure
Authors: Liu Zhongxiang , Zuo Bingqing , Lin Jianyang , Sun Zhixiao , Hu Hang , Yin Yuan , Yang Shuanying
Published: February 2025

Background

The prognostic prediction of patients with hypercapnic respiratory failure holds significant clinical value. The objective of this study was to develop and validate a predictive model for predicting survival in patients with hypercapnic respiratory failure.

Methods

The study enrolled a total of 697 patients with hypercapnic respiratory failure, including 565 patients from the First People’s Hospital of Yancheng in the modeling group and 132 patients from the People’s Hospital of Jiangsu Province in the external validation group. The three selected models were random survival forest (RSF), DeepSurv, a deep learning-based survival prediction algorithm, and Cox Proportional Risk (CoxPH). The model’s predictive performance was evaluated using the C-index and Brier score. Receiver operating characteristic curve (ROC), area under ROC curve (AUC), and decision curve analysis (DCA) were employed to assess the accuracy of predicting the prognosis for survival at 6, 12, 18, and 24 months.

Results

The RSF model (c-index: 0.792) demonstrated superior predictive ability for the prognosis of patients with hypercapnic respiratory failure compared to both the traditional CoxPH model (c-index: 0.699) and DeepSurv model (c-index: 0.618), which was further validated on external datasets. The Brier Score of the RSF model demonstrated superior performance, consistently measuring below 0.25 at the 6-month, 12-month, 18-month, and 24-month intervals. The ROC curve confirmed the superior discrimination of the RSF model, while DCA demonstrated its optimal clinical net benefit in both the modeling group and the external validation group.

Conclusion

The RSF model offered distinct advantages over the CoxPH and DeepSurv models in terms of clinical evaluation and monitoring of patients with hypercapnic respiratory failure.
Association of Helicobacter pylori related chronic atrophic gastritis and gastric cancer risk: a literature review
Authors: Zhang Zefeng , Chen Sitong , Li Shudan , Zheng Yadan , Mai Lifei , Zhang Xiaoguang
Published: February 2025

Chronic atrophic gastritis (CAG) is considered to be closely related to Helicobacter pylori (H. pylori) infection and characterized by the atrophy and/or intestinal metaplasia (IM) of the gastric mucosa in pathology. CAG is often regarded as the precancerous lesion of gastric cancer and H. pylori infection stimulates the development of atrophy and IM and the progression of gastric cancer through the persistent effect acting on the gastric mucosa, including releasing inflammatory factors such as Interleukin-8(IL-8). From the molecular biology perspective, growing evidence shows that H. pylori probably induce the expression of NF-κB, miR-204, miR-27a, hnRNPA2B1, and JARID1B, which play crucial roles in the progression of CAG into gastric cancer. In addition, H. pylori can increase Epstein-Barr virus (EBV) infection, and the co-infection will jointly increase gastric cancer risk. Furthermore, H. pylori induces cellular senescence and promotes atrophy progression and finally increases the gastric cancer risk. This review aims to explore the carcinogenic mechanisms of H. pylori related CAG in order to provide theoretical foundations for the pathogenesis mechanism and early detection and prevention of gastric cancer.
Immunomagnetic enrichment coupled to PAX8/TP53 molecular pathology approach increases sensitivity in the detection of ovarian cancer cells in ascites
Authors: Kurelac Ivana , Sollazzo Manuela , De Luise Monica , Nanetti Francesca , Lanteri Laura , D’Angelo Luigi , Cavina Beatrice , Corrà Simona , Miglietta Stefano , Milioni Sara , Luppi Elena , Iommarini Luisa , Di Costanzo Stella , Ricciardi Anna Maria , Coluccelli Sara , Maloberti Thais , Grillini Marco , Coadă Camelia Alexandra , Perrone Anna Myriam , De Iaco Pierandrea , de Biase Dario , Ragazzi Moira , Gasparre Giuseppe , Porcelli Anna Maria
Published: February 2025

High-grade serous ovarian carcinoma (HGSOC) is one of the deadliest malignancies in female population and the cause of 70% of all ovarian cancer-related deaths. Among its hallmarks, the fluid accumulation in the peritoneal cavity, or ascites, is a peculiar pathological sign during late stages and in recurrent patients. Besides cancer cells, ascitic fluids contain a heterogeneous cellular composition, representing a precious source to dissect molecular mechanisms underlying invasion and metastatization or find new biomarkers to predict therapy response. However, malignant cells are often a minority population in ascites making the detection and analysis of cancer cells a challenge. Here we propose a combinatorial approach for the detection of malignant cells in OC ascites based on TP53 deep sequencing and PAX8 cytological staining. In addition, we improve the procedure by implementing a cancer cell enrichment step, increasing the sensitivity in the detection of neoplastic fraction and potentiating downstream research and diagnostics applications.
Odor induced functional connectivity alteration of POC-anterior frontal cortex-medial temporal cortex in patients with mild cognitive impairment
Authors: Li Weiping , Zhou Jianan , Li Shuying , Wu Min , Zhu Yajing , Chen Qian , Chen Futao , Ma Xuefeng , Zhang Xin , Wang Zhengge , Lu Jiaming , Zhang Bing
Published: February 2025

Background

Mild cognitive impairment (MCI) is associated with an increased risk of dementia in older adults. Olfactory impairment may indicate prodromal dementia, yet its underlying mechanisms are not fully understood. This study aimed to investigate the alterations in functional connectivity (FC) of odor-induced olfactory neural circuits in MCI patients.

Methods

The study included 39 MCI patients and 42 normal controls (NCs). All subjects underwent cognitive assessments, olfactory behavior tests, and odor-based functional magnetic resonance imaging (fMRI). Differences in FC within olfactory circuits were analyzed using the generalized psychophysiological interaction (gPPI) method.

Results

Mild cognitive impairment patients showed significant cognitive deficits, including lower scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), alongside impairments in episodic memory, visuospatial memory, executive function, language, attention, olfactory threshold, and total olfactory function. Compared to NCs, MCI patients exhibited reduced activation in the bilateral primary olfactory cortex (bPOC) during olfactory stimulation. Odor-induced bPOC activation correlated with olfactory thresholds across the cohort. During odor stimulation, MCI patients showed increased FC from the bPOC to the right anterior frontal lobe, particularly the middle frontal gyrus (MFG) and superior frontal gyrus (SFG). Conversely, FC from the right anterior frontal lobe to the medial temporal cortex, including the fusiform and parahippocampal gyri, was reduced in MCI patients. Increased FC from the bPOC to the right SFG/MFG negatively correlated with episodic memory, while decreased FC to the right fusiform/parahippocampal gyri positively correlated with attention, language ability, and olfactory identification.

Conclusion

This study indicates that impaired FC within the primary olfactory cortex (POC)-anterior frontal cortex-medial temporal cortex circuit is a sensitive neuroimaging marker for early MCI identification. The primary dysfunction appears in the POC, suggesting that FC alterations from this region may provide novel diagnostic and therapeutic avenues for early intervention.
Apolipoprotein E genotype is associated with island sign in lobar intracerebral hemorrhage
Authors: Yang Qiong , Sun Haixin , Ma Xinran , Tang Lu , Liu Xiaolu , Huang Xin , Huang Xiao , Chen Yong , Tian Danyang , Zeng Xiangzhu , Li Nan , Wang Wenzhi , Fan Dongsheng
Published: February 2025

Background

The island sign is a predictor of hematoma expansion and worse outcomes in patients of spontaneous primary intracerebral hemorrhage (ICH). The biological mechanism of the island sign remains unclear, but its presence might be influenced by the underlying vasculopathy related to Apolipoprotein E (APOE) genotypes. Therefore, we aimed to research the association between APOE genotypes and the island sign.

Methods

We enrolled patients with primary supratentorial ICH in a multicenter cohort in northern China with baseline noncontrast CT images performed within 14 days after symptoms onset and APOE genotype available. The island sign was rated on the CT images according to validated criteria. Univariable and multivariable analyses were used to identify the association between APOE genotypes and the island sign, stratified by the ICH location.

Results

Among 460 patients enrolled, 122 were lobar ICH. In all patients, after adjusting for age, sex, hypertension, and time to CT, the presence of the APOE ε4 allele (OR 2.020, 95% CI 1.064–3.834, p = 0.032) was associated with the island sign, whereas the presence of the APOE ε2 allele (OR 0.734, 95% CI 0.339–1.593, p = 0.435) was not. After stratifying by ICH location, multivariable analysis revealed that APOE ε4 (OR 3.510, 95% CI 1.393–8.846, p = 0.008), rather than ε2 (OR 0.621, 95% CI 0.203–1.901, p = 0.404), was associated with the island sign in lobar ICH patients. Neither the ε2 nor the ε4 allele was associated with the island sign among nonlobar ICH patients.

Conclusion

The APOE ε4 allele was associated with the island sign in lobar ICH patients. Our findings indicate that the presence of the island sign may be influenced by the underlying vasculopathy related to APOE ε4, which increases amyloid deposition in the cerebral vasculature.
Facilitation of non-nociceptive bladder activity and suppression of somatic afferent inhibition by hypogastric afferents in cats
Authors: Shen Bing , Wang Jicheng , Tai Changfeng , Beckel Jonathan M.
Published: February 2025

Introduction

While it is well known that the sensory arm of the micturition reflex is mediated by A-δ afferents in the pelvic nerve, the urinary bladder is also innervated by afferents in the hypogastric nerve (HGN), whose role in micturition is less well understood. We have recently determined that stimulation of HGN afferents can facilitate nociceptive bladder activity in the cat induced by intravesical instillation of acetic acid. The aim of the present study, then, was to determine if activation of HGN afferents could similarly facilitate normal bladder activity in the cat, evoked by saline distension. Additional experiments examined if HGN stimulation could modulate the inhibitory effects of tibial or pudendal neuromodulation on bladder capacity.

Methods

Continuous infusion cystometry was performed in 9 (4 male, 5 female) α-chloralose anesthetized cats in which the HGNs were transected bilaterally. Bipolar electrodes were used to stimulate the central end of the cut HGNs at varying intensities (1-15 V) and frequencies (1-40 Hz) during bladder filling with saline (1-2 ml/min) until a micturition contraction occurred. Tripolar cuff electrodes were also placed on the left pudendal and left tibial nerve to examine the effect of neuromodulation on bladder capacity during cystometry.

Results

Hypogastric nerve stimulation (HGNS) at 30 Hz and 15 V significantly reduced bladder capacity to 80.01 ± 3.86% of control. Tibial or pudendal nerve stimulation (5 Hz, 2 T) significantly increased bladder capacity to 187.6 ± 20.2% or 193.8 ± 19.0% of control, respectively. Simultaneous HGNS significantly reduced the efficacy of tibial nerve neuromodulation (reduced to 158.7 ± 18.7% of control) and but only partially suppressed the bladder inhibition induced by pudendal neuromodulation (reduced to 161.9 ± 18.0% of control).

Conclusion

These results suggest that HGN afferents (possibly C-fiber nociceptors) from the bladder or other pelvic organs may facilitate normal bladder activity to cause bladder overactivity. Additionally, HGN afferents may influence the efficacy of tibial or pudendal neuromodulation therapy in treating OAB.
Adherence to the planetary health diet index and metabolic dysfunction-associated steatotic liver disease: a cross-sectional study
Authors: Qiu Xin , Shen Shuang , Jiang Nizhen , Lu Donghong , Feng Yifei , Yang Guodong , Xiang Bangde
Published: February 2025

Backgrounds

Adherence to the Planetary Health Diet Index (PHDI) has been shown to benefit both individual health and the planet. However, its impact on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains unclear. This study aimed to investigate the relationship between PHDI adherence and the MASLD risk.

Methods

We analyzed a cohort of 15,865 adults (aged ≥18 years) using data from the National Health and Nutrition Examination Survey (NHANES, 2005–2018). The PHDI was derived from 24-h dietary assessments and comprised the scores of 15 food groups. Multivariate logistic regression was used to investigate the association between PHDI and MASLD, while restricted cubic spline (RCS) regression and threshold analysis were employed to explore potential non-linear relationship. Subgroup analyses were conducted to assess the influence of various demographic and clinical characteristics on the observed associations. Mediation analysis was performed to evaluate the indirect effect of PHDI on MASLD, and weighted quantile sum (WQS) regression was used to assess the influence of individual PHDI nutrients on MASLD.

Results

Among the cohort, 6,125 individuals were diagnosed with MASLD. Multivariate logistic regression revealed that a higher quintile of PHDI was significantly associated with reduced MASLD risk in the fully adjusted model (OR = 0.610, 95%CI 0.508–0.733, p < 0.001). Notably, nonlinear relationships between PHDI and MASLD risk were observed through RCS analysis (p = 0.002). Subgroup analyses indicated that PHDI was particularly effective in reducing MASLD risk among females, those with higher education attainment, and those living with a partner. WQS regression identified saturated fatty acids as the most significant factor contributing to MASLD risk (weight = 0.313). Additionally, BMI and waist circumference (81.47 and 87.66%, respectively) partially mediated the association between PHDI and MASLD risk, suggesting that the effect of PHDI on MASLD operates, in part, through its impact on BMI and waist circumference. The association between PHDI and MASLD remained robust across multiple sensitivity analyses.

Conclusion

Our findings indicate that adherence to PHDI is linked to a lower risk of MASLD, providing crucial insights for strategies aimed at mitigating the MASLD epidemic while simultaneously fostering environmental sustainability.
Breast acinic cell carcinoma with weak progesterone receptor expression: a case report and literature review
Authors: Bai Caiyun , Xin Xiaodong , Yang Yisen , Qu Fengjiang , Fan Zhimin
Published: February 2025

Rationale

Acinic cell carcinoma (AcCC) of the breast is an extremely rare malignant epithelial tumor characterized by acini cell differentiation, clinical low-grade malignancy, and a molecular triple-negative subtype.

Patient concern

A 47-year-old female presented with a 1-month history of a painless mass in her right breast.

Diagnosis

Ultrasound imaging, mammography and magnetic resonance imaging revealed a lesion, approximately 3.0cm×1.5cm in size, in the right breast, which was considered to be a malignancy. After the surgery, the AcCC of the breast was confirmed histologically.

Interventions

Right breast mastectomy and sentinel lymph node biopsy were performed. Adjuvant chemotherapy included 4 cycles of doxorubicin hydrochloride (Adriamycin) and cyclophosphamide followed by 4 cycles of docetaxel (Taxotere).

Outcomes

The patient was discharged from the hospital after surgery. There was no sign of recurrence during a 9-month follow-up period.

Lessons

Acinic cell carcinoma (AcCC) of the breast is an extremely rare malignant epithelial tumor that can be accurately diagnosed based on histopathologic morphology and immunohistochemistry. The weak positive progesterone receptor (PR) expressed in this case is extremely rare, which may provide a new research direction for the endocrine therapy of AcCC. Both AcCC and microglandular adenosis(MGA) exhibit microglandular growth, and the relationship between them remains unclear. Differentiation between them not only relies on histomorphology and pathological immunohistochemistry but also depends on clinical manifestations and other presentations. Optimal treatment of AcCC is the same as that for invasive breast cancer. The prognosis is generally good, with adjuvant therapy after surgery.
Influence of CAR T-cell therapy associated complications
Authors: Umair Mohammad Mussab , Lai Xun , Xue YuanBo , Yao Hong
Published: February 2025

Since the introduction of chimeric antigen receptor (CAR) T-cell therapy, it has elicited an immense response in both targeted and residual cancers. Its clinical efficacy is often accompanied by a group of side effects that may become serious because of factors such as tumor burden, the extent of lymphodepletion, and the type of co-stimulus. It is also crucial to know the common toxicities associated with CAR T-cell therapy, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cardiotoxicity, metabolic disorders, pulmonary toxicity, macrophage activation syndrome (MAS), prolonged cytopenia, coagulation disorders, and potential off-target effects on various organs. If not well managed, these can be fatal. However, knowledge about molecular pathways, calcineurin inhibitors, IL-6 receptor antagonists, steroids, suppression of nitric oxide synthase, various therapeutic approaches, and other recent advances have been developed to mitigate the fatal results of various short-term and chronic adverse events related to CAR T-cell therapy. This study provides a comprehensive perspective on contemporary management strategies and presumed causative processes of CAR T-cell-related adverse effects, albeit with several limitations. When CAR T-cell complications, costs, and challenges of toxicity management are properly considered, the CAR T-cell therapy of the future will include a number of toxicity-escaping options.
Experiencing fertility preservation in adolescence – a qualitative interview study indicating gender disparities in AYAs diagnosed with cancer
Authors: Rodriguez-Wallberg Kenny A. , Nilsson Hanna , Folmerz Maria , Lundqvist Erica , Granberg Lisa , Armuand Gabriela
Published: February 2025

Introduction

Fertility counselling on options for fertility preservation is increasingly implemented for children and adolescents at time of cancer diagnosis. Sperm cryopreservation has been standard of care for male patients during several decades and the procedure is not expected to delay the onset of cancer treatment. However, oocyte cryopreservation in female adolescents remains controversial, the reasons include the need of ovarian stimulation, gynecological exams and interventions, in all a potentially distressing experience for patients without previous experience of this type of examination or without previous sexual debut. With this study we wished to investigate how adolescent cancer patients experience fertility preservation procedures aiming at semen banking or oocyte cryopreservation.

Methods

Adolescent patients diagnosed with cancer that underwent fertility preservation at the Reproductive Medicine Clinic of Karolinska University Hospital were invited to participate in the study. Inclusion required the ability to communicate in Swedish or English. Exclusion criteria were current age under 15 at time of the interview and ongoing cancer treatment. The study had a qualitative study design and phenomenological approach with semi-structured individual face-to-face interviews. Ten interviews with six female and four male study participants were conducted between June and August 2023.

Results

The analysis resulted in three identified main themes: Communication about the risk of infertility and the fertility preservation, Freezing gametes - the process and healthcare encounters, and The decision to preserve gametes for one’s own sake. Gender specific gaps in communication about fertility risks and fertility preservation procedures were found, with young females expressing a wish for improved communication and reporting experiences of discomfort during the procedures needed for oocyte cryopreservation, whereas young men were generally satisfied with their experience. Limitations include a risk of responder bias since not all patients who were contacted agreed to interview.

Discussion

Although gender disparities were identified in this study, fertility preservation was perceived as a positive experience and mitigated fertility-related distress in both male and female adolescent patients. Our study adds to the scarce literature on adolescents of both sexes undergoing fertility preservation and underscores the importance of specialized communication in fertility counselling and treatment of AYAs diagnosed with cancer.
A novel compound, SYHA1813, inhibits malignant meningioma growth directly by boosting p53 pathway activation and impairing DNA repair
Authors: Lan Yanjie , Li Shenglan , Wang Jiachen , Yang Xin , Wang Can , Huang Mengqian , Zhang Rong , Chen Feng , Li Wenbin
Published: February 2025

Introduction

Meningioma is a common tumor of the central nervous system but effective therapies for malignant meningiomas are still lacking. Therefore, the development of novel therapeutic reagents is urgently needed. SYHA1813 is a novel compound and our previous study demonstrated its potent anti-tumor activity on glioblastoma through the inhibition of macrophages and human umbilical vein endothelial cells (HUVECs). However, the precise functional role of SYHA1813 in meningiomas remains unclear.

Method

We aimed to investigate the direct tumor-inhibitory effects of SYHA1813 on meningioma both in vitro and in vivo, and explore its potential molecular mechanisms.

Results

Our results showed that SYHA1813 suppressed the proliferation, colony formation, migration, and invasion of meningioma cells in vitro. Furthermore, we found SYHA1813 induced G2/M cell cycle arrest, apoptosis, and cellular senescence. Mechanistically, RNA-seq revealed that SYHA1813 activated the P53 pathway and impaired DNA repair. In vivo, SYHA1813 effectively inhibited the growth of meningioma xenografts in a mouse model. Additionally, in an ongoing first-inhuman phase I trial, this patient with recurrent meningioma provided preliminary clinical evidence supporting the anti-tumor activity of SYHA1813.

Discussion

This study unveiled a novel antitumor mechanism of SYHA1813, showing its ability to directly target and kill meningioma cells in vitro and in vivo. Our findings highlighted the promising potential of SYHA1813 as a therapeutic agent for treating malignant meningiomas.
The family of glutathione peroxidase proteins and their role against biotic stress in plants: a systematic review
Authors: do Carmo Santos Maria Luíza , Silva Santos Ariana , Pereira Silva de Novais Diogo , dos Santos Lopes Natasha , Pirovani Carlos Priminho , Micheli Fabienne
Published: February 2025

Introduction

Glutathione peroxidases (GPXs) are extensively studied for their indispensable roles in eliminating reactive oxygen species by catalyzing the reduction of hydrogen peroxide or lipid peroxides to prevent cell damage. However, knowledge of GPXs in plants still has many gaps to be filled. Thus, we present the first systematic review (SR) aimed at examining the function of GPXs and their protective role against cell death in plants subjected to biotic stress.

Methods

To guide the SR and avoid bias, a protocol was developed that contained inclusion and exclusion criteria based on PRISMA guidelines. Three databases (PubMed, Science Direct, and Springer) were used to identify relevant studies for this research were selected.

Results

A total of 28 articles related to the proposed objective. The results highlight the importance of GPXs in plant defense against biotic stress, including their role in protecting against cell death, similar to the anti-apoptotic GPXs in animals. Data from gene expression and protein accumulation studies in plants under various biotic stresses reveal that GPXs can both increase resistance and susceptibility to pathogens. In addition to their antioxidant functions, GPXs act as sensors and transmitters of H2O2 signals, integrating with the ABA signaling pathway during stress.

Discussion

These findings show that GPXs delay senescence or reinforce physical barriers, thereby modulating resistance or susceptibility to pathogens. Additionally, their functions are linked to their cellular localization, which demonstrates an evolutionary relationship between the studied isoforms and their role in plant defense. This information broadens the understanding of molecular strategies involving GPX isoforms and provides a foundation for discussions and actions aimed at controlling necrotrophic and/or hemibiotrophic pathogens.