bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Red Blood Cell Distribution Width and In‐Hospital Mortality among Congestive Heart Failure Patients with Diabetes among Patients in the Intensive Care Unit: A Retrospective Cohort Study
Authors: Zhang Kai , Han Yu , Gao Yu Xuan , Gu Fang Ming , Cai Tianyi , Hu Rui , Gu Zhao Xuan , Liang Jia Ying , Zhao Jia Yu , Gao Min , Li Bo , Cui Dan
Published: July 2024

Background. Elevated red blood cell distribution width (RDW) levels are strongly associated with an increased risk of mortality in patients with congestive heart failure (CHF). Additionally, heart failure has been closely linked to diabetes. Nevertheless, the relationship between RDW and in‐hospital mortality in the intensive care unit (ICU) among patients with both congestive heart failure (CHF) and diabetes mellitus (DM) remains uncertain. Methods. This retrospective study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC‐IV) database, a comprehensive critical care repository. RDW was assessed as both continuous and categorical variables. The primary outcome of the study was in‐hospital mortality at the time of hospital discharge. We examined the association between RDW on ICU admission and in‐hospital mortality using multivariable logistic regression models, restricted cubic spline analysis, and subgroup analysis. Results. The cohort consisted of 7,063 patients with both DM and CHF (3,135 females and 3,928 males). After adjusting for potential confounders, we found an association between a 9% increase in mortality rate and a 1 g/L increase in RDW level (OR = 1.09; 95% CI, 1.05∼1.13), which was associated with 11 and 58% increases in mortality rates in Q2 (OR = 1.11, 95% CI: 0.87∼1.43) and Q3 (OR = 1.58, 95% CI: 1.22∼2.04), respectively, compared with that in Q1. Moreover, we observed a significant linear association between RDW and in‐hospital mortality, along with strong stratified analyses to support the findings. Conclusions. Our findings establish a positive association between RDW and in‐hospital mortality in patients with DM and CHF.
Diagnostic Accuracy of Urinary Biomarkers in Periodontitis: A Systematic Review and Meta‐Analysis
Authors: Fratini Adriano , Izzetti Rossana , Riccetti Nicola , Gennai Stefano , Graziani Filippo , Marchetti Enrico
Published: July 2024

Background. Biomarkers can be measured in various biological samples. Urine is among the most useful biofluids for routine testing, and several experimental and clinical studies support its role as a tool for the diagnosis and prevention of various diseases. The present systematic review aimed to examine periodontitis‐specific urine biomarkers that could have a diagnostic relevance and to provide a qualitative assessment of the current literature. Materials and Methods. Relevant studies identified from PubMed, Embase, Cochrane Library, and Scopus databases were examined to answer the following PECO question: “Could the concentration of specific metabolites in the urine be related to periodontal health and what is their diagnostic accuracy?”. Quality of included studies was rated using ROBINS‐I tool. Meta‐analysis was conducted on available quantitative data. Results. After the screening of 768 titles, five studies were included in qualitative synthesis. The studies included referred to the evaluation of 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) and neopterin. Meta‐analysis was conducted for neopterin concentration on data available in four studies involving 129 participants. Higher concentrations of neopterin were found in periodontitis‐affected patients compared to controls and patients treated for periodontitis. Conclusions. The literature appears controversial in attributing a role to neopterin and 8‐OHdG as periodontal biomarkers, highlighting the need for further clinical studies on this topic. While some studies report variations in 8‐OHdG and neopterin levels in periodontally affected patients versus either controls or periodontally treated patients, the level of evidence appears still limited to draw firm conclusions (PROSPERO CRD42020222681).
Surface Damage Detection and Localization for Bridge Visual Inspection Based on Deep Learning and 3D Reconstruction
Authors: Ni Youhao , Mao Jianxiao , Wang Hao , Xi Zhuo , Chen Zhengyi
Published: July 2024

In the process of infrastructure construction in recent decades, there exist millions of bridges in service that need safety inspection for performance assessment. Currently, computer vision and deep learning‐based surface damage detection methods can achieve classification and localization of damages at the image level, but achieving precise localization in three‐dimensional space is more challenging. To overcome aforementioned limitations, this study proposes a three‐stage method of bridge surface damage detection and localization based on three‐dimensional (3D) reconstruction. In stage 1, the UAV flight path planning of the bridge is carried out, and the 3D reconstruction model of the bridge is formed based on the structure from motion (SfM) algorithm. In stage 2, you‐only‐look‐once version 7 (YOLOv7) network is adopted to detect multiple damages, and scale invariant feature transform (SIFT) detector is used to match the identical damage in image level. In stage 3, based on solution of epipolar geometric constraint, the matched damage was mapped to the 3D model, and the 3D damage localization is realized and visualized. The quality of the 3D model has been analyzed, and it is recommended that inspection distance is determined at 20 m. Moreover, the reconstruction model of bridges achieves centimeter‐level positioning accuracy, and the positioning accuracy of damage reaches the meter level. The mapped model effectively showcases surface damages, providing bridge owners with intuitive insights.
Multidimensional Fragmentomics Enables Early and Accurate Detection of Colorectal Cancer
Authors: Cao Yuepeng , Wang Nannan , Wu Xuxiaochen , Tang Wanxiangfu , Bao Hua , Si Chengshuai , Shao Peng , Li Dongzheng , Zhou Xin , Zhu Dongqin , Yang Shanshan , Wang Fufeng , Su Guoqing , Wang Ke , Wang Qifan , Zhang Yao , Wang Qiangcheng , Yu Dongsheng , Jiang Qian , Bao Jun , Yang Liu
Published: July 2024

Colorectal cancer is frequently diagnosed in advanced stages, highlighting the need for developing approaches for early detection. Liquid biopsy using cell-free DNA (cfDNA) fragmentomics is a promising approach, but the clinical application is hindered by complexity and cost. This study aimed to develop an integrated model using cfDNA fragmentomics for accurate, cost-effective early-stage colorectal cancer detection. Plasma cfDNA was extracted and sequenced from a training cohort of 360 participants, including 176 patients with colorectal cancer and 184 healthy controls. An ensemble stacked model comprising five machine learning models was employed to distinguish patients with colorectal cancer from healthy controls using five cfDNA fragmentomic features. The model was validated in an independent cohort of 236 participants (117 patients with colorectal cancer and 119 controls) and a prospective cohort of 242 participants (129 patients with colorectal cancer and 113 controls). The ensemble stacked model showed remarkable discriminatory power between patients with colorectal cancer and controls, outperforming all base models and achieving a high area under the receiver operating characteristic curve of 0.986 in the validation cohort. It reached 94.88% sensitivity and 98% specificity for detecting colorectal cancer in the validation cohort, with sensitivity increasing as the cancer progressed. The model also demonstrated consistently high accuracy in within-run and between-run tests and across various conditions in healthy individuals. In the prospective cohort, it achieved 91.47% sensitivity and 95.58% specificity. This integrated model capitalizes on the multiplex nature of cfDNA fragmentomics to achieve high sensitivity and robustness, offering significant promise for early colorectal cancer detection and broad patient benefit.

 Significance: The development of a minimally invasive, efficient approach for early colorectal cancer detection using advanced machine learning to analyze cfDNA fragment patterns could expedite diagnosis and improve treatment outcomes for patients.

See related commentary by Rolfo and Russo, p. 3128
Hyperactive Dendritc Cells Redirect Aged Antitumor Immunity
Authors: Chen Alex C.Y. , Sen Debattama R.
Published: July 2024

Aging is one of the biggest risk factors for cancer development. More than 85% of all cancers occur in individuals above 55 years old, often accompanied by age-associated immune defects. Previous studies on the tumor microenvironment during aging have identified several factors, such as the roles of fibroblasts, immunosuppression, and metastasis. However, the aging-associated defects in antitumor immunity, particularly with regard to T cells, remain underexplored. Recent findings by Zhivaki and colleagues suggest that age-related immune defects affecting antitumor responses involve reduced levels of CD8+ T cells and compromised dendritic cell (DC) functions such as antigen presentation and migration. Their study demonstrates that a hyperactive DC vaccine can restore DC functions in older mice. Furthermore, these hyperactive DCs, characterized by increased IL1β production and better migratory capability to the lymph node, promote the development of cytolytic CD4+ T cells exhibiting Th1-like phenotypes. This research reveals mechanisms underlying the response to hyperactive DC vaccines in older mice and highlights the critical role of cytolytic CD4+ T cells as substitutes for CD8+ T cells in driving antitumor immunity and achieving long-term tumor control in older mice.
Table S3 from ZNF397 Deficiency Triggers TET2-Driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer
Authors: Xu Yaru , Yang Yuqiu , Wang Zhaoning , Sjöström Martin , Jiang Yuyin , Tang Yitao , Cheng Siyuan , Deng Su , Wang Choushi , Gonzalez Julisa , Johnson Nickolas A. , Li Xiang , Li Xiaoling , Metang Lauren A. , Mukherji Atreyi , Xu Quanhui , Tirado Carla R. , Wainwright Garrett , Yu Xinzhe , Barnes Spencer , Hofstad Mia , Chen Yu , Zhu Hong , Hanker Ariella B. , Raj Ganesh V. , Zhu Guanghui , He Housheng H. , Wang Zhao , Arteaga Carlos L. , Liang Han , Feng Felix Y. , Wang Yunguan , Wang Tao , Mu Ping
Published: July 2024

Table S3. Significantly Enriched or Depleted Signaling Pathways in GSEA Analysis
Data from ZNF397 Deficiency Triggers TET2-Driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer
Authors: Xu Yaru , Yang Yuqiu , Wang Zhaoning , Sjöström Martin , Jiang Yuyin , Tang Yitao , Cheng Siyuan , Deng Su , Wang Choushi , Gonzalez Julisa , Johnson Nickolas A. , Li Xiang , Li Xiaoling , Metang Lauren A. , Mukherji Atreyi , Xu Quanhui , Tirado Carla R. , Wainwright Garrett , Yu Xinzhe , Barnes Spencer , Hofstad Mia , Chen Yu , Zhu Hong , Hanker Ariella B. , Raj Ganesh V. , Zhu Guanghui , He Housheng H. , Wang Zhao , Arteaga Carlos L. , Liang Han , Feng Felix Y. , Wang Yunguan , Wang Tao , Mu Ping
Published: July 2024

Abstract
Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming that allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified zinc finger protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a ten-eleven translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the resistance to AR-targeted therapies in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity.

Significance: This study reveals a bifurcated role of ZNF397, and a TET2–driven epigenetic mechanism regulating tumor lineage plasticity and therapy response in prostate cancer, enhances the understanding of drug resistance, and unveils a new therapeutic strategy for overcoming androgen receptor-targeted therapy resistance.
Data from A Kinome-Wide Synthetic Lethal CRISPR/Cas9 Screen Reveals That mTOR Inhibition Prevents Adaptive Resistance to CDK4/CDK6 Blockade in HNSCC
Authors: Goto Yusuke , Koshizuka Keiichi , Ando Toshinori , Izumi Hiroki , Wu Xingyu , Sato Kuniaki , Ishikawa Tomohiko , Ford Kyle , Feng Xiaodong , Wang Zhiyong , Arang Nadia , Allevato Michael M. , Kishore Ayush , Mali Prashant , Gutkind J. Silvio
Published: July 2024

Abstract
The comprehensive genomic analysis of the head and neck squamous cell carcinoma (HNSCC) oncogenome revealed the frequent loss of p16INK4A (CDKN2A) and amplification of cyclin D1 genes in most human papillomavirus–negative HNSCC lesions. However, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown modest effects in the clinic. The aberrant activation of the PI3K/mTOR pathway is highly prevalent in HNSCC, and recent clinical trials have shown promising clinical efficacy of mTOR inhibitors (mTORi) in the neoadjuvant and adjuvant settings but not in patients with advanced HNSCC. By implementing a kinome-wide CRISPR/Cas9 screen, we identified cell-cycle inhibition as a synthetic lethal target for mTORis. A combination of mTORi and palbociclib, a CDK4/6-specific inhibitor, showed strong synergism in HNSCC-derived cells in vitro and in vivo. Remarkably, we found that an adaptive increase in cyclin E1 (CCNE1) expression upon palbociclib treatment underlies the rapid acquired resistance to this CDK4/6 inhibitor. Mechanistically, mTORi inhibits the formation of eIF4G–CCNE1 mRNA complexes, with the consequent reduction in mRNA translation and CCNE1 protein expression. Our findings suggest that mTORi reverts the adaptive resistance to palbociclib. This provides a multimodal therapeutic option for HNSCC by cotargeting mTOR and CDK4/6, which in turn may halt the emergence of palbociclib resistance.
Significance:
A kinome-wide CRISPR/Cas9 screen identified cell-cycle inhibition as a synthetic lethal target of mTORis. A combination of mTORi and palbociclib, a CDK4/6-specific inhibitor, showed strong synergistic effects in HNSCC. Mechanistically, mTORis inhibited palbociclib-induced increase in CCNE1.
Diagnostic Accuracy and Safety of Nonsurgical Biopsy for Diagnosing Pulmonary Ground-Glass Opacities: A Systematic Review and Meta-Analysis
Authors: Zhou Mengyun , Zhang Meng , Jin Zhou , Zhao Xiang , Yu Kunyao , Huang Junfang , Wang Guangfa , Cheng Yuan
Published: July 2024

Introduction: Previous meta-analyses have explored the diagnostic accuracy and safety of computed tomography-guided percutaneous lung biopsy of ground-glass opacities (GGOs). However, no research investigated the role of nonsurgical biopsies (including transbronchial approaches). Additionally, studies reporting the diagnostic accuracy of GGOs with different characteristics are scarce, with no quantitative assessment published to date. We performed a systematic review to explore the diagnostic accuracy and safety of nonsurgical biopsy for diagnosing GGOs, especially those with higher ground-glass components and smaller nodule sizes. Methods: A thorough literature search of four databases was performed to compile studies evaluating both or either of the diagnostic accuracy and complications of nonsurgical biopsy for GGOs. A bivariate random-effects model and random-effect model were utilized for data synthesis. The methodological quality of the studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: Nineteen eligible studies with a total of 1,379 biopsy-sampled lesions were analyzed, of which 1,124 were confirmed to be malignant. Nonsurgical biopsy reported a pooled sensitivity of 0.89, a specificity of 0.99, and a negative predictive value (NPV) of 60.3%. The overall sensitivity, specificity, and NPV of nonsurgical biopsy for diagnosing GGOs according to GGO component were 0.90, 0.99, and 77.2% in pure GGOs; 0.87, 0.99, and 67.2% in GG-predominant lesions; and 0.89, 1.00, and 44.1% in solid-predominant lesions, respectively. Additionally, the diagnostic sensitivity was better in lesions ≥20 mm than in small lesions (0.95 vs. 0.88). Factors that contributed to higher sensitivity were the use of a coaxial needle system and CT fluoroscopy but not the needle gauge. The summary sensitivity of core needle biopsy (CNB) was not significantly higher than fine needle aspiration (FNA) (0.92 vs. 0.84; p = 0.42); however, we found an increased incidence of hemorrhage in CNB compared with FNA (60.9 vs. 14.2%; p = 0.012). Conclusion: Nonsurgical biopsy for diagnosing GGOs shows high sensitivity and specificity with an acceptably low risk of complications. However, negative biopsy results are unreliable in excluding malignancy, necessitating resampling or subsequent follow-up. The applicability of our study is limited due to significant heterogeneity, indirect comparisons, and the paucity of data on bronchoscopic approaches, restricting the generalizability of our findings to patients requiring transbronchial biopsies.
The Immunosuppressive Drug LF15-0195 Acts Also on Glomerular Lesions, by a Change in Cytoskeleton Distribution in Podocyte
Authors: Le Berre Ludmilla , Tilly Gaëlle , Pilet Paul , Brouard Sophie , Dantal Jacques
Published: July 2024

Introduction: Buffalo/Mna rats spontaneously develop nephrotic syndrome (NS) which recurs after renal transplantation. The immunosuppressive drug LF15-0195 can promote regression of the initial and post-transplantation nephropathy via induction of regulatory T cells. We investigate if this drug has an additional effect on the expression and localization of podocyte specific proteins. Methods: Buffalo/Mna kidney samples were collected before and after the occurrence of proteinuria, and after the remission of proteinuria induced by LF15-0195 treatment and compared by quantitative RT-PCR, Western blot, electron, and confocal microscopy to kidney samples of age-matched healthy rats. Cytoskeleton changes were assessed in culture by stress fibers induction by TNFα. Results: We observed, by electron microscopy, a restoration of foot process architecture in the LF15-0195-treated Buff/Mna kidneys, consistent with proteinuria remission. Nephrin, podocin, CD2AP, and α-actinin-4 mRNA levels remained low during the active disease in the Buff/Mna, in comparison with healthy rats which increase, while podocalyxin and synaptopodin transcripts were elevated before the occurrence of the disease but did not differ from healthy animals after. No difference in the mRNA and protein expression between the untreated and the LF15-0195-treated proteinuric Buff/Mna were seen for these 6 proteins. No changes were observed by confocal microscopy in the protein distribution at a cellular level, but a more homogenous distribution similar to healthy rats, was observed within the glomeruli of LF15-0195-treated rats. In addition, LF15-0195 could partially restore actin cytoskeleton of endothelial cells in TNFα-induced-cell stress experiment. Conclusion: The effect of LF15-0195 treatment appears to be mediated by 2 mechanisms: an immunomodulatory effect via regulatory T cells induction, described in our previous work and which can act on immune cell involved in the disease pathogenesis, and an effect on the restoration of podocyte cytoskeleton, independent of expression levels of the proteins involved in the slit diaphragm and podocyte function, showed in this article.
QUALITY OF LIFE AND PSYCHOLOGICAL CHANGES IN BARIATRIC SURGERY: AN OBSERVATIONAL STUDY
Authors: Ramos-Bachiller Beatriz , López-Gómeza Juan J. , García-Calvo Susana , Torres-Torres Beatriz , Primo-Martín David , Pinto-Fuentes Pilar , Pacheco-Sánchez David , Uribe-Ladrón De Cegama Fernando , de Luis Daniel A.
Published: July 2024

Introduction: Candidates for bariatric surgery may have psychiatric disorders that must be evaluated. The aim of this study was to describe the psychological state and quality of life (QoL) of patients with obesity awaiting bariatric surgery prior to surgical procedure and one year after surgery.
Methods: A longitudinal retrospective observational study was carried out in 71 patients awaiting bariatric surgery. Anthropometric data were collected, and the following were evaluated before and one year after the intervention: 44 patients were evaluated to rule out personality disorder, using the Salamanca Questionnaire of Personality Disorders; eating disorder, with the Bulimia Test of Edinburgh (BITE); depression, using the Beck Depression Inventory (BDI); and 71 patients were evaluated QoL, with the "Short Form Health Survey"(SF-36).
Results: A total of 34.1% (n=15) of patients presented personality disorder (Group B most frequent). 31.8% (n=14) obtained scores suggesting anomalous food behavior (6.8% n=3 severe). According to the BDI, 43.2% (n=19) showed low mood prior to the intervention. Lower scores were obtained when evaluating QoL for physical functioning (physical function:56.81±24.9; physical problems:66.76±37.64). One year after the intervention, QoL improved in those patients who underwent the sleeve gastrectomy (SG).
Conclusions: Patients with bariatric surgery more frequently presented with Type B and C personalities. One year after bariatric surgery an improvement in QoL test was observed. Patients who underwent SG technique showed better mean scores than those after bilopancreatic diversion (BPD).
Cognitive and behavioural profile of patients with Amyotrophic Lateral Sclerosis spectrum in the Indian Context
Authors: Srivastava Kosha , Arshad Faheem , Mujawar Wasim Javed , Cranberg Lee , Rajeshwaran Jamuna , Afsar Mohammad , Thanissery Nithin , Desai Vaishnavi , Keerthana Bangalore Somashekar , Shubhangi Balu , Vengalil Seena , Nashi Saraswati , Baskar Dipti , Polavarapu Kiran , Preethish-Kumar Veeramani , Alladi Suvarna , Nalini Atchayaram
Published: July 2024

Introduction
Amyotrophic lateral sclerosis (ALS) is characterized by motor, cognitive and behavioral impairment. There is a paucity of evidence about the cognitive/behavioral features of ALS patients from India. We aimed to investigate the cognitive/behavioral profile of ALS spectrum disorders in the Indian context.
Methods
Sixty patients with ALS spectrum and 40 age, gender and education matched healthy controls were recruited. The scales used were: Addenbrooke’s Cognitive Examination (ACE–III) Clinical Dementia Rating (CDR) scale, and Frontal Systems Behavior Scale (FrSBe).
Results
The median age of the overall cohort was 54 years (IQR, 14), and male-to-female ratio was 2.5:1. Median duration of illness of the cohort was 12 months (IQR, 12). Patients were classified as ALS with: normal cognition (ALS-cn, n=21), mild cognitive or behavioral deficits (ALS-ci/bi, n=28), and Frontotemporal Dementia (ALS-FTD, n=11). ALS-cn had poorer scores compared to healthy controls in global cognition, memory, and language (p<0.05). ALS-ci/bi performed poorer than healthy controls on all cognitive domains (p < 0.05). ALS-FTD had poorer scores than healthy controls and ALS-cn on all cognitive domains (p< 0.001). Behavioral assessment showed an increase in apathy among all subtypes. ALS-FTD showed significant worsening in disinhibition and executive function compared to ALS-cn and ALSci/bi.
Conclusion
Our findings suggest that there are key cognitive and behavior characteristics in Indian patients with ALS spectrum. This further strengthens the evidence of a cognitive continuum in ALS and FTD in a diverse context and highlights the importance of meticulous evaluation and correct diagnosis that would assist in better management.
Baseline Depressive Symptoms as a Predictor of Incident Dementia in a Prospectively Followed Cohort of Elders with Essential Tremor
Authors: Berry Diane S. , Ghanem Ali , McGurn Margaret M. , Huey Edward D. , Cosentino Stephanie , Louis Elan D.
Published: July 2024

Introduction: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. Methods: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants’ baseline depression scores. Results: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02–1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02–1.25, p = 0.02). Conclusion: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population.
The Role of Infant Gut Microbiota Modulation by Perinatal Maternal Probiotic Intervention in Atopic Eczema Risk Reduction
Authors: Puisto Reetta , Gómez-Gallego Carlos , Collado Maria Carmen , Turta Olli , Isolauri Erika , Rautava Samuli
Published: July 2024

Introduction: Probiotics have shown potential in reducing the occurrence of atopic eczema in high-risk infants. We aimed here to assess whether the preventive effect of maternal probiotic administration stems from compositional changes in early gut microbiota. Methods: This study included 46 mother-infant pairs from an original randomized controlled trial assessing the impact of maternal probiotic intervention with either the combinations of Lacticaseibacillus rhamnosus LPR and Bifidobacterium longum BL999, or Lacticaseibacillus paracasei ST11 and Bifidobacterium longum BL999, or placebo beginning 2 months before expected delivery and ending 2 months after birth. All children were vaginally delivered, full term and breastfed. During the 2-year follow-up period, the children were clinically evaluated by physicians for atopic eczema, and their gut microbiota was profiled at 1 and 6 months of age by 16S rRNA gene sequencing using an Illumina sequencing platform. Results: Altogether, 19 of 46 children developed atopic eczema by the age of 2 years. At 1 and 6 months of age, gut microbial diversity was similar between children who developed atopic eczema and their healthy controls, but at the age of 6 months, children who developed atopic eczema manifested with significantly higher relative abundance of Clostridia. Probiotic intervention did not significantly influence microbial diversity, and the effects on microbial composition were not consistent with the changes associated with the development of atopic eczema. Conclusion: The reduction of the risk of atopic eczema achieved by perinatal maternal probiotic intervention does not seem to require substantial gut microbiota modulation.
Association of Gum Treatment with Cognitive Decline and Dementia Risk among Older Adults with Periodontal Symptoms: A 12-Year Prospective Cohort Study
Authors: Qi Xiang , Zhu Zheng , Wang Katherine , Zheng Yaguang , Li An , Wu Bei
Published: July 2024

Introduction: This study examines the associations of gum treatment with cognitive decline and dementia risk among older adults with periodontal symptoms in the USA. Methods: A cohort of 866 adults aged ≥50 with periodontal symptoms was recruited for the 2008 Health and Retirement Study “Dental Health Experimental Module” and followed until 2020. Cognitive function was assessed with the Telephone Interview for Cognitive Status (TICS). Dementia status was ascertained with the Langa-Weir algorithm based on TICS scores and proxy assessments. Linear mixed-effects model and multivariable Cox regression models were utilized to analyze the associations of gum treatment with cognitive decline and the risk of dementia, respectively. Results: Of 866 participants (mean age 67.7, 61.4% women), 105 (12.1%) developed dementia with a median follow-up of 9 (IQR, 6–10) years. The dementia incidence rates were lower in the group with gum treatment (7.4 vs. 12.9 per 1,000 person-years). Compared with participants who did not have gum treatment, those with gum treatment experienced a decline in TICS score that was on average 0.025 (95% CI, 0.005–0.044) points less per year and a 38% lower incidence of dementia (hazard ratio, 0.62; 95% CI, 0.41–0.93). These associations were consistent across participants with a different severity of periodontal symptoms and sociodemographic characteristics (age, sex, race, ethnicity, and education) except for income levels. Conclusion: Prompt gum treatment for older adults with periodontal symptoms may be beneficial for their cognitive health.
Drug-Induced Hair Loss: Analysis of the Food and Drug Administration’s Adverse Events Reporting System Database
Authors: Hill Rachel C. , Zeldin Steven D. , Lipner Shari R.
Published: July 2024

Introduction: Drug-induced hair loss is one of several causes of hair loss commonly seen in clinical practice, and it is often a daunting task to determine a potential culprit drug when a patient is taking numerous medications. Our objective was to identify drugs responsible for hair loss, using the Food and Drug Administration’s Adverse Events Reporting System (FAERS) database, a compilation of drug-related adverse events (AEs). Methods: Using the FAERS database, we queried all domestic reports with the reaction term “alopecia” listed as an AE in patients ≥18 years old from April 1, 1968, to September 29, 2023. Using descriptive statistics, individual agents were grouped by drug class. Results: We analyzed a total of 39,346 hair loss AE reports related to a single agent. Immunomodulatory agents and monoclonal antibodies represented the highest proportion of AE reports for alopecia, followed by hair loss drugs, contraceptives, and antitumor necrosis factor (anti-TNF) biologics. Conclusion: In sum, we showed that immunomodulatory agents and monoclonal antibodies, hair loss drugs, including minoxidil and finasteride, contraceptives, kinase inhibitors, and anti-TNF drugs are most frequently associated with hair loss AEs in the FAERS database. Because many of these drugs are not prescribed primarily for dermatologic indications, our study provides guidance for dermatologists in identifying common medications associated with alopecia.
Kabuki Syndrome and Charcot-Marie-Tooth Disease Co-Occurrence: Unique Case with Novel Variant
Authors: Kablan Ahmet , Erturkmen Aru Esma
Published: July 2024

Introduction: Kabuki syndrome (KS) is a rare syndrome, characterized by dysmorphic features, congenital abnormalities, and developmental problems. The primary genetic causes are variants in the KMT2D and KDM6A genes. There are few KS patients with KDM6A variants, especially in Turkey. Charcot-Marie-Tooth (CMT) disease, with various subtypes, is the most common inherited peripheral neuropathy. Case Presentation: We present a case of a 7-year-old girl with characteristic dysmorphic features, neonatal hypotonia, developmental delay, and short stature. Exome sequencing revealed a novel heterozygous variant in KDM6A, along with a concurrent suspected diagnosis of CMT disease with CNV analysis, not previously reported in the literature. PMP22 duplication was later confirmed in the patient and symptomatic mother with MLPA test. Conclusion: We report a unique case of dual diagnosis with a novel de novo heterozygous variant in KDM6A and PMP22 duplication in the same patient, highlighting the additive use of exome sequencing for CNVs and, moreover, unraveling the complexity of rare diseases, particularly when multiple conditions coexist.
Combination Epicardial Adipose Tissue and left atrial Low Voltage Areas Predicting Atrial Fibrillation Recurrence after radiofrequency ablation
Authors: Qiu Bowen , Li Fei , Sang Chuanyi , Shen Jianfan , Shao Yameng , Chen Wenshu , Hu Xiaoqin , Li Chengzong , Hu Chunfeng , Zhang Chaoqun , Wang Zhirong , Chen Minglong
Published: July 2024

Background: Atrial fibrillation (AF) is a common arrhythmia, with radiofrequency catheter ablation (RFCA) being first-line therapy. However, the high rate of post-ablation recurrence necessitates the identification of predictors for recurrence risk. Left atrial low-voltage areas (LA-LVASs), reflecting atrial fibrosis, have been confirmed to be related to recurrence of atrial fibrillation. Recently, epicardial adipose tissue (EAT) has been studied due to its role in initiating and maintaining atrial fibrillation. In this study, we try to evaluate the significance of the combined use of LA-EAT and percentage of LA-LVAs (LA-LVAs%) for predicting the recurrence of atrial fibrillation.
Methods: A total of 387 patients with AF who had undergone RFCA for the first time were followed up for 3, 6, and 12 months. They were divided into two groups: the recurrence group (n=90) and the non-recurrence group (n=297). Before the ablation, all patients underwent computed tomography angiography (CTA) examination of the left atrium, and the left atrial epicardial adipose tissue (LA-EAT) was measured using medical software (Advantage Workstation 4.6, GE, USA). After circumferential pulmonary vein isolation， a three-dimensional mapping system was used to map the left atrial endocardium and evaluate the LA-LVAs in sinus rhythm.
Results: After a median follow-up of 10.2 months, 90 patients developed AF recurrence after RFCA. Compared to patients without recurrence, the volume of LA-EAT (33.45±13.65 vs. 26.27±11.38; p<0.001) and the LA-LVAs% (1.60% (0%, 9.99%) vs. 0.00% (0%, 2.46%); p<0.001) were significantly higher. Multivariate analysis indicated that non-paroxysmal AF, LA-EAT volume, and LA-LVAs% were independent predictors. Compared to LA-EAT volume (AUC 0.655; specificity 0.675; sensitivity 0.586) or LA-LVAs% (AUC 0.659; specificity 0.836; sensitivity 0.437), the combined use of LA-EAT volume and LA-LVAs% offers higher accuracy for predicting AF recurrence after ablation (AUC 0.738; specificity 0.761; sensitivity 0.621).
Conclusion: The combined LA-EAT and LA-LVAs% can effectively predict the risk of AF recurrence after radiofrequency ablation.
Systems Biology and Novel Biomarkers for the Early Detection of Diabetic Kidney Disease
Authors: Villalvazo Priscila , Villavicencio Carlos , Gonzalez de Rivera Marina , Fernandez-Fernandez Beatriz , Ortiz Alberto
Published: July 2024

Diabetic kidney disease is the most common driver of chronic kidney disease (CKD)-associated mortality and kidney replacement therapy. Despite recent therapeutic advances (sodium glucose co-transporter 2 [SGLT2] inhibitors, finerenone), the residual kidney and mortality risk remains high for patients already diagnosed of having CKD (i.e., estimated glomerular filtration rate <60 mL/min/1.73 m2 or urinary albumin:creatinine ratio >30 mg/g). The challenge for the near future is to identify patients at higher risk of developing CKD to initiate therapy before CKD develops (primary prevention of CKD) and to identify patients with CKD and high risk of progression or death, in order to intensify therapy. We now discuss recent advances in biomarkers that may contribute to the identification of such high-risk individuals for clinical trials of novel primary prevention or treatment approaches for CKD. The most advanced biomarker from a clinical development point of view is the urinary peptidomics classifier CKD273, that integrates prognostic information from 273 urinary peptides and identifies high-risk individuals before CKD develops.
Hand Motor Dysfunction Is Associated with Both Subjective and Objective Cognitive Impairment across the Dementia Continuum
Authors: Rudd Kaylee D. , Lawler Katherine , Callisaya Michele L. , Bindoff Aidan D. , Chiranakorn-Costa Sigourney , Li Renjie , McDonald James S. , Salmon Katharine , Noyce Alastair J. , Vickers James C. , Alty Jane
Published: July 2024

Introduction: Motor dysfunction is an important feature of early-stage dementia. Gait provides a non-invasive biomarker across the dementia continuum. Gait speed and rhythm aid risk stratification of incident dementia in subjective cognitive impairment (SCI) and are associated with cognitive domains in mild cognitive impairment (MCI) and dementia. However, hand movement analysis, which may be more accessible, has never been undertaken in SCI and rarely in MCI or dementia. We aimed to address this gap and improve understanding of hand motor-cognitive associations across the dementia continuum. Methods: A total of 208 participants were recruited: 50 with dementia, 58 MCI, 40 SCI, and 60 healthy controls. Consensus diagnoses were made after comprehensive gold-standard assessments. A computer key-tapping test measured frequency, dwell-time, rhythm, errors, and speed. Associations between key-tapping and cognitive domains and diagnoses were analysed using regression. Classification accuracy was measured using area under receiver operating characteristic curves. Results: Hand frequency and speed were associated with memory and executive domains (p ≤ 0.001). Non-dominant hand rhythm was associated with all cognitive domains. Frequency, rhythm, and speed were associated with SCI, MCI, and dementia. Frequency and speed classified ≥94% of dementia and ≥88% of MCI from controls. Rhythm of the non-dominant hand classified ≥86% of dementia and MCI and 69% of SCI. Conclusion: Our findings show hand motor dysfunction occurs across the dementia continuum and, similar to gait, is associated with executive and memory domains and with cognitive diagnoses. Key-tapping performance differentiated dementia and MCI from healthy controls. More research is required before recommending key-tapping as a non-invasive motor biomarker of cognitive impairment.
Mortality of Epilepsy in Chinese Populations: A Comprehensive Review
Authors: Zhou Xiaowen , Ding Ding , Wang Wenzhi , Zhou Dong , Sander Josemir W.
Published: July 2024

Background: Premature mortality is a significant part of the epilepsy burden and may vary across populations, especially between high-income and lower- and middle-income countries. People with epilepsy in China are approximately a fifth of the global population with epilepsy. Previous studies were unlikely to represent the situation in China due to limitations in design, methods, sample size, follow-up time, and other inherent population heterogeneity. Summary: By summarising the evidence on the mortality characteristics in Chinese populations with epilepsy in the last 6 decades, we found a median mortality rate of 14.7 (6.8–74.4)/1,000 person-years and a median standardised mortality ratio (SMR) of 4.4 (2.6–12.9) in population-based studies, and a median mortality rate of 12.3 (9.5–101.5)/1,000 person-years and a median SMR of 3.0 (1.5–5.1) in hospital-based studies. Vascular diseases, complications of diabetes, and accidental injuries were the leading causes of death. Risk factors for mortality were reported as older age, male, longer duration, and higher frequency of seizures. Case fatality ratios of status epilepticus in adults were higher than in children, and both increased with follow-up time. Mortality in people with symptomatic epilepsy was high and varied across different primary diseases. Key Messages: The highest mortality rate and sudden unexpected death in epilepsy (SUDEP) incidence were reported from the least developed areas in China. Accidental injuries were the most common causes of epilepsy-related deaths, while the incidence of SUDEP may be underestimated in Chinese populations. Further research is warranted to improve the understanding of premature mortality risk so that preventative measures can be introduced to improve the situation.
Risk of Cancer in Patients with Congenital Heart Disease: A Systematic Review and Meta-Analysis
Authors: Ren Lijuan , Feng Mei , Luo Yulan , Chen Yu
Published: July 2024

Introduction: There has been remarkable progress in both diagnosis and treatment of patients with congenital heart disease (CHD), with an increasing number of survivors. Whether patients with CHD are more likely to develop cancer is still a controversial issue. This study aimed to quantitatively estimate the association between patients with CHD and the risk of developing cancer through meta-analysis. Methods: Web of Science, PubMed, and Embase databases were searched from inception to September 2023 to identify potentially relevant case-control studies and cohort studies that reported risk estimates and confidence intervals (CIs). RevMan software was used to analyze the pooled effect size and test for heterogeneity. The random effect and fixed effect models were applied to the study period. Egger’s test was performed to examine publication bias. Results: We analyzed six studies, consisting of 2 case-control studies and 4 cohort studies comprising 276,124 participants. The overall pooled hazard risk for cancer in patients with CHD was 1.71 (95% CI: 1.28–2.28; p < 0.01), with significant heterogeneity (I2 = 97%, p < 0.01). The quantitative analysis of studies indicates that patients with CHD have an increased risk of developing cancer, even after adjusting for chromosomal disorders. Conclusion: Our study highlights the importance of controlling modifiable factors in cancer prevention and emphasizes the need for health education for patients with CHD in primary care. Given the limited number of studies included in this analysis, further research is needed to accurately quantify the cancer risk of exposed versus unexposed CHD.
Integrating Artificial Intelligence-Driven Wearable Technology in Oncology Decision-Making: A Narrative Review
Authors: Birla Meghna , Rajan  , Roy Prabhat Gautam , Gupta Ishaan , Malik Prabhat Singh
Published: July 2024

Background: Clinical decision-making in oncology is a complex process influenced by numerous disease-related factors, patient demographics, and logistical considerations. With the advent of artificial intelligence (AI), precision medicine is undergoing a shift toward more precise and personalized care. Wearable device technology complements this paradigm shift by offering continuous monitoring of patient vitals, facilitating early intervention, and improving treatment adherence. The integration of these technologies promises to enhance the quality of oncological care, making it more responsive and tailored to individual patient needs, thereby enabling wider implementation of such applications in the clinical setting. Summary: This review article addresses the integration of wearable devices and AI in oncology, exploring their role in patient monitoring, treatment optimization, and research advancement along with an overview of completed clinical trials and utility in different aspects. The vast applications have been exemplified using several studies, and all the clinical trials completed till date have been summarized in Table 2. Additionally, we discuss challenges in implementation, regulatory considerations, and future perspectives for leveraging these technologies to enhance cancer care and radically changing the global health sector. Key Messages: AI is transforming cancer care by enhancing diagnostic, prognostic, and treatment planning tools, thus making precision medicine more effective. Wearable technology facilitates continuous, noninvasive monitoring, improving patient engagement and adherence to treatment protocols. The combined use of AI and wearables aids in monitoring patient activity, assessing frailty, predicting chemotherapy tolerance, detecting biomarkers, and managing treatment adherence. Despite these advancements, challenges such as data security, privacy, and the need for standardized devices persist. In the foreseeable future, wearable technology can hold significant potential to revolutionize personalized oncology care, empowering clinicians to deliver comprehensive and tailored treatments alongside standard therapy.
Prevalence and Temporal Trends of Epilepsy in Children: A Retrospective Birth Cohort Study
Authors: Driollet Bénédicte , Buajitti Emmalin , Ahmed Asma M. , Hutcheon Jennifer A. , Rosella Laura , Yang Seungmi
Published: July 2024

Objective: Epilepsy is one of the most common chronic neurologic diseases in children; however, few recent studies examine the prevalence of epilepsy and its evolution over time according to birth or maternal characteristics. The aim of the study was to examine the prevalence of epilepsy in children born between 2002 and 2020 and the temporal trends by year of birth, in Ontario, Canada, overall, and according to maternal and birth characteristics. Methods: We included all in-hospital deliveries between 2002 and 2020 (N = 2,343,482) in Ontario, Canada, using linked administrative health dataset. We estimated the overall prevalence of epilepsy diagnosed before the age of 18 years, by birth and maternal characteristics. For temporal trend analyses, we restricted our population to children born up to 2012 (N = 1,405,271) and examined the prevalence of epilepsy diagnosed by age 8 by their year of birth, using Poisson regression. Results: The overall prevalence of epilepsy in our cohort was 8.1 per 1,000 live births (95% CI: 8.0–8.2). Prevalence was higher for boys, for children born preterm, with congenital malformations, from multiple pregnancies, from mothers born in Canada, and for children living in deprived areas. Epilepsy prevalence diagnosed by age 8 increased slightly between 2002 and 2012 cohorts (6.9 [95% CI: 6.2–7.6] to 7.3 [95% CI: 6.6–8.1] per 1,000 live births, respectively). Differences by gestational age as gradient and socioeconomic characteristics were persistent and stable over time, while those by pregnancy plurality and sex decreased. Significance: In a large population-based birth cohort in Canada, we observed a slight increase in epilepsy prevalence over time among children born in 2002 and those born in 2012 and persistent disparities by gestational age, socioeconomic position, and maternal immigration status. This study highlights the need for continued surveillance of rates to see if this increasing trend is persistent, to understand the potential causes behind it, and to understand the persistence of these disparities.