bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationships of lifestyle behaviours and body fat distribution on diabetic microvascular complications: a Mendelian randomization study
Authors: Guo Nuojin , Shi Hekai , Zhao Hongmei , Abuduani Yierfan , Chen Da , Chen Xishuang , Wang Hua , Li Peicheng 
Published: July 2024

ObjectivesTo determine the causal correlations of lifestyle behaviours and body fat distribution on diabetic microvascular complications through a Mendelian Randomization (MR).MethodsGenetic variants significantly associated with lifestyle behaviours, abdominal obesity, generalized obesity and diabetic microvascular complications were extracted from the UK Biobank (UKB) and FinnGen. The inverse variance weighted (IVW) method was regarded as the primary method. The main results were presented in odds ratio (OR) per standard deviation (SD) increase, and a series of sensitivity analyses were also conducted to validate the stability of the results.ResultsThere was a positive causal correlation between smoking and the development of diabetic retinopathy (OR = 1.16; 95%CI: 1.04–1.30; p = 0.01). All of the indicators representing abdominal obesity had a statistically significant causal association with diabetic microvascular complications. Concerning generalized obesity, there were significant causal associations of body mass index (BMI) on diabetic nephropathy (OR = 1.92; 95%CI: 1.58–2.33; p &lt; 0.001), diabetic retinopathy (OR = 1.27; 95%CI: 1.15–1.40; p &lt; 0.001), and diabetic neuropathy (OR = 2.60; 95%CI: 1.95–3.45; p &lt; 0.001). Other indicators including leg fat mass (left), and arm fat mass (left) also had a significant positive causality with diabetic microvascular complications.ConclusionOur findings suggested that smoking has a genetically causal association with the development of diabetic retinopathy rather than diabetic nephropathy and diabetic neuropathy. In addition, both abdominal obesity and generalized obesity are risk factors for diabetic microvascular complications. To note, abdominal obesity represented by waist circumference (WC) is the most significant risk factor.
Intratumoral high endothelial venules in solid tumors: a pooled study
Authors: Wang Bin , Han Yin , Liu Jie , Zhang Xinyao , Deng Yaotiao , Jiang Yu 
Published: July 2024

ObjectiveWe performed this pooled analysis for the first time to comprehensively explore the prognostic value of tumor-associated high endothelial venules (TA-HEVs) and determine their relationships with clinicopathological features in solid tumors.MethodsFour online databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched to identify studies assessing the effect of TA-HEVs on prognosis or clinicopathological features. Hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate survival outcomes, including overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). The association between TA-HEV status and clinicopathological characteristics was assessed by odds ratios (ORs) combined with 95% CIs. Subgroup analysis was conducted to explore sources of heterogeneity. The sensitivity analysis was performed to evaluate the stability of our findings. Meanwhile, Funnel plots were employed to visually evaluate potential publication bias, and both Begg’s and Egger’s tests were adopted to quantitatively determine publication bias.ResultsA total of 13 retrospective cohort studies, involving 1,933 patients were finally included in this meta-analysis. Effect-size pooling analysis showed that the positivity of TA-HEVs was related to improved OS (pooled HR: 0.75, 95% CI: 0.62-0.93, P&lt;0.01), and DFS (pooled HR = 0.54, 95% CI = 0.41-0.72, P&lt; 0.01). However, TA-HEV positivity in solid tumors was not linked to PFS (pooled HR = 0.75, 95% CI 0.34-1.64, P = 0.47) or CSS (pooled HR: 0.58, 95% CI: 0.04-7.58, P= 0.68). Further subgroup analysis demonstrated that ethnicity and source of HR were the main factors contributing to heterogeneity. Moreover, TA-HEVs were inversely associated with lymph node metastasis and distant metastasis, but were positively related to worse tumor differentiation. However, TA-HEVs were not significantly correlated with sex, LVI, clinical stage, and depth of invasion. Sensitivity analysis suggested that the pooled results were stable and reliable, with no significant publication bias in all included articles.ConclusionsThis is the first comprehensive analysis of the prognostic value of TA-HEVs in solid tumors using existing literature. Overall, our study demonstrated a significant correlation between TA-HEVs and prognosis as well as clinicopathological features. TA-HEVs may serve as novel immune-related biomarkers for clinical assessments and prognosis prediction in solid tumors.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD42023394998.
Analysis revealed the molecular mechanism of oxidative stress-autophagy-induced liver injury caused by high alkalinity: integrated whole hepatic transcriptome and metabolome
Authors: Shang Xinchi , Geng Longwu , Wei Hai jun , Liu Tianqi , Che Xinghua , Li Wang , Liu Yuhao , Shi Xiao dan , Li Jianhong , Teng Xiaohua , Xu Wei 
Published: July 2024

IntroductionHigh-alkalinity water is a serious health hazard for fish and can cause oxidative stress and metabolic dysregulation in fish livers. However, the molecular mechanism of liver damage caused by high alkalinity in fish is unclear. MethodsIn this study, 180 carp were randomly divided into a control (C) group and a high-alkalinity (A25) group and were cultured for 56 days. High-alkalinity-induced liver injury was analysed using histopathological, whole-transcriptome, and metabolomic analyses. ResultsMany autophagic bodies and abundant mitochondrial membrane damage were observed in the A25 group. High alkalinity decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activity and the total antioxidant capacity (T-AOC) and increased the malondialdehyde (MDA) content in liver tissues, causing oxidative stress in the liver. Transcriptome analysis revealed 61 differentially expressed microRNAs (miRNAs) and 4008 differentially expressed mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that mammalian target of rapamycin (mTOR), forkhead box O (FoxO), mitogen-activated protein kinase (MAPK), and the autophagy signalling pathway were the molecular mechanisms involved. High alkalinity causes oxidative stress and autophagy and results in autophagic damage in the liver. Bioinformatic predictions indicated that Unc-51 Like Kinase 2 (ULK2) was a potential target gene for miR-140-5p, demonstrating that high alkalinity triggered autophagy through the miR-140-5p–ULK2 axis. Metabolomic analysis revealed that the concentrations of cortisol 21-sulfate and beta-aminopropionitrile were significantly increased, while those of creatine and uracil were significantly decreased. DiscussionThe effects of high alkalinity on oxidative stress and autophagy injury in the liver were analysed using whole-transcriptome miRNA-mRNA networks and metabolomics approaches. Our study provides new insights into liver injury caused by highly alkaline water.
Temporal changes in mouse hippocampus transcriptome after pilocarpine-induced seizures
Authors: Popova Evgenya Y. , Kawasawa Yuka Imamura , Leung Ming , Barnstable Colin J. 
Published: July 2024

IntroductionStatus epilepticus (SE) is a seizure lasting more than 5 min that can have lethal consequences or lead to various neurological disorders, including epilepsy. Using a pilocarpine-induced SE model in mice we investigated temporal changes in the hippocampal transcriptome.MethodsWe performed mRNA-seq and microRNA-seq analyses at various times after drug treatment.ResultsAt 1 h after the start of seizures, hippocampal cells upregulated transcription of immediate early genes and genes involved in the IGF-1, ERK/MAPK and RNA-PolII/transcription pathways. At 8 h, we observed changes in the expression of genes associated with oxidative stress, overall transcription downregulation, particularly for genes related to mitochondrial structure and function, initiation of a stress response through regulation of ribosome and translation/EIF2 signaling, and upregulation of an inflammatory response. During the middle of the latent period, 36 h, we identified upregulation of membrane components, cholesterol synthesis enzymes, channels, and extracellular matrix (ECM), as well as an increased inflammatory response. At the end of the latent period, 120 h, most changes in expression were in genes involved in ion transport, membrane channels, and synapses. Notably, we also elucidated the involvement of novel pathways, such as cholesterol biosynthesis pathways, iron/BMP/ferroptosis pathways, and circadian rhythms signaling in SE and epileptogenesis.DiscussionThese temporal changes in metabolic reactions indicate an immediate response to injury followed by recovery and regeneration. CREB was identified as the main upstream regulator. Overall, our data provide new insights into molecular functions and cellular processes involved at different stages of seizures and offer potential avenues for effective therapeutic strategies.
Spinal manipulation and mobilization forces delivered treating sciatica: a case report
Authors: Siciliano Theodore B. , Gudavalli Maruti R. , Kruse Ralph 
Published: July 2024

IntroductionAccurately measuring the forces applied during spinal manipulation and its biomechanical effects on the spine are critically important in current research. This single case report discusses the potential benefit of accurately monitoring manipulative forces in treating low back pain with sciatica. The type of force-based spinal manipulation used to manage this case was Cox Technic flexion distraction decompression (CTFDD) spinal manipulation care, along with other ancillary modalities.MethodsThe treatment plan, in this case, was primarily force-based CTFDD, equal-force bi-directional traction (EqFT), pre-modulated electrical muscle stimulation (EMS), infrared light therapy (ILT), and a home stretching and strengthening program.Clinical findingsInitially, the case study patient presented with complaints of left lumbar spine pain, which radiated into the left buttock, down the left leg, accompanied by an inability to dorsiflex the left foot. The patient was concerned with this condition as the left leg pain and left lower extremity motor deficit were having a profound effect on the patient’s ability to perform activities of daily living and work. The patient was recommended to undergo spinal decompression surgery, which the patient did not want, and elected to exhaust all alternative, non-surgical treatments first.Diagnosis, intervention, and outcomesA diagnosis of sciatica with a sequestered disk fragment and left lower extremity motor deficit was rendered through objective physical examination results and a review of a lumbar MRI study. Past interventions included prescription medications, physical rehabilitation, chiropractic, pain management, and neurosurgical consultation. All past interventions prior to initiating CTFDD care provided minimal subjective and/or objective clinical improvement. This patient had a positive clinical outcome from a force-based CTFDD treatment plan along with other modalities consisting of pre-modulated EMS, ILT, and a home stretching and strengthening program.ConclusionForce-based CTFDD spinal manipulation, along with other modalities consisting of pre-modulated EMS, ILT, and a home stretching and strengthening program, has been found to be an alternative, non-surgical treatment for discogenic sciatica. Continued research is needed on force-based CTFDD spinal manipulation to further evaluate the neurological and biomechanical effects of the forces and motion applied to the spine and determine health benefits for the treatment of low back pain.
Case report: Pulmonary sarcomatoid carcinoma demonstrating rapid growth on follow-up CT
Authors: Tu Li , Xie Hong , Zhan Lianshan , Yang Yushi , Chen Tingting , Hu Na , Du Xiaojun , Zhou Shi 
Published: July 2024

BackgroundThe tumor growth rate and tumor volume doubling time are crucial parameters in diagnosing and managing lung lesions. Pulmonary sarcomatoid carcinoma (PSC) is a unique and highly malignant subtype of lung cancer, with limited documentation on its growth feature. This article aims to address the gap in knowledge regarding a PSC’s growth patterns by describing the characteristics of a confirmed case using computed tomography, thereby enhancing the understanding of this rare disease.Case presentationA 79-year-old man was transferred to our center presenting with a mild cough, blood-tinged sputum, and a malignant nodule in the left upper lobe. Chest CT revealed a solid nodule in the left upper lobe. A follow-up CT ten days later showed a significant increase in the size of the nodule, accompanied by ground-glass opacity in the surrounding lung. The rapid preoperative growth of the nodule suggested a non-neoplastic lesion, and intraoperative frozen pathology also considered the possibility of tuberculosis. Subsequently, a left upper apical-posterior segment (S1 + 2) resection was performed. Postoperative tumor pathology confirmed the diagnosis of pulmonary sarcomatoid carcinoma with extensive giant cell carcinoma and necrosis. Immunohistochemistry indicated approximately 60% PD-L1 positive and genetic testing revealed a MET mutation. The patient was discharged with oral crizotinib targeted therapy, and his condition remained stable postoperatively. The patient is currently undergoing regular follow-up at our hospital, with no evidence of distant metastasis or recurrence.ConclusionPulmonary sarcomatoid carcinoma can exhibit rapid tumor growth on imaging, and PSC should be considered in the differential diagnosis for lesions that present with a fast growth rate. Timely and appropriate treatment for PSC may lead to a good prognosis.
Implications of tumor-positive sentinel lymph nodes in single vs multiple nodal basins in melanoma
Authors: Reyes Emiliano , Lourdault Kristel , Ramiscal Judi Anne , Stern Stacey , Essner Richard 
Published: July 2024

BackgroundMelanoma patients’ prognosis is based on the primary tumor characteristics and the tumor status of the regional lymph nodes. The advent of lymphoscintigraphy with SLN biopsy (SLNB) has shown that melanoma can drain to multiple nodal basins but the significance of multiple basins (vs. one basin) with tumor-positive sentinel lymph node(s) (+SLN) of similar tumor burden has not been shown. We examined the impact of the number of nodal basins with +SLN (+basin) in melanoma patients and its significance for patients’ prognosis and survival.Study designWe identified 1,915 patients with +SLN from two randomized surgical clinical trials: Multicenter Selective Lymphadenectomy Trials I and II. Patient groups were divided based on number of +SLNs and number of +basins. Disease-free survival (DFS), distant disease-free survival (DDFS) and melanoma-specific survival (MSS) were compared with the Kaplan-Meier method and log-rank tests. Univariable and multivariable analyses were performed using Cox proportional hazard regressions.ResultsAmong the 1,915 patients, 1,501 had only one +SLN (78%) in one basin and 414 (22%) had multiple +SLNs: 340 located in one basin and 74 in multiple basins. Among patients with multiple +SLNs, those with multiple +basins have a worse DFS, DDFS and MSS than those with a single basin (p ≤ 0.0001 for all comparisons). MSS was significantly different based on AJCC stages: AJCC IIIA and IIIB (p ≤ 0.001 and 0.0287, respectively).ConclusionOur results suggest that the number of tumor-positive basins may be important for staging and in understanding the biology of lymph node metastases.
What are the benefits of therapeutic drug monitoring in the optimization of adalimumab therapy? a systematic review and meta-analysis up to 2022
Authors: Li Yun , Xie Cheng , Ding Xiaoliang , Wu Ziyang , Zhang Jingjing , Zhu Jianguo , Miao Liyan 
Published: July 2024

AimsPersistent uncertainties exist surrounding the therapeutic drug monitoring (TDM) of adalimumab in clinical settings. To address these issues, we conducted a systematic review to assess the current evidence regarding the benefits of TDM for adalimumab.MethodsPubMed, EMBASE, and Cochrane Databases were searched from inception to October 2022. The trials regarding to the list three key questions were considered: 1) Could routine proactive TDM assist in improving outcomes in patients receiving adalimumab? 2) Could reactive TDM assist in guiding subsequent treatment strategies for patients with treatment failure to adalimumab? 3) Could TDM assist in informing dose reduction or discontinuation in patients with low disease activity or in remission treated with adalimumab? Two reviewers independently selected the studies and extracted the data. Meta-analysis was performed to calculate the relative risk (RR) and 95% confidence interval (CI).ResultsA total of 9 studies was included in this review. For proactive TDM, meta-analysis indicated that proactive TDM (n = 163/257, 63.42%) showed no significant superiority over reactive TDM and/or conventional management (n = 336/606, 55.44%) in achieving and/or maintaining clinical remission by random effects model (RR: 1.24, 95% CI 0.98–1.58, I2 = 73%). There were three studies that supporting the reactive TDM, low drug levels in the absence of anti-drug antibodies (ADA) strongly indicate the need for dose intensification, and infliximab is a feasible choice for patients with low drug levels and ADA positivity. While swapping to another class should be considered in patients with adequate drug levels. In addition, TDM can help clinicians optimize dosing schedules and prevent overtreatment in patients who have achieved low disease activity and sufficient drug concentrations, with no predictive value for successful adalimumab discontinuation.ConclusionCurrent evidence suggests that proactive TDM is numerically but not statistically significant superiority over reactive TDM and/or conventional management. Reactive TDM can aid in understanding treatment failure and developing subsequent therapy. For patients reaching low disease activity and remission, TDM can help successful dose reduction, while it cannot inform the successful drug discontinuation. However, existing trials are limited, and more well-designed trials are necessary to clarify the role of TDM in adalimumab treatment.
Development and validation of the Alimetry Gut-Brain Wellbeing Survey: a novel patient-reported mental health scale for patients with chronic gastroduodenal symptoms
Authors: Law Mikaela , Pickering Isabella , Humphrey Gayl , Sebaratnam Gabrielle , Schamberg Gabriel , Simpson Katie , Varghese Chris , Du Peng , Daker Charlotte , Huang I-Hsuan , Khalsa Sahib S. , Gharibans Armen , O'Grady Greg , Andrews Christopher N. , Calder Stefan 
Published: July 2024

ObjectiveThere is currently a lack of validated questionnaires designed specifically to assess mental health within patients with chronic gastroduodenal symptoms. This research describes the multi-phase process used to develop and validate a novel mental health scale for patients with chronic gastroduodenal symptoms, the Alimetry® Gut-Brain Wellbeing (AGBW) Survey.MethodsA patient-centered multi-phase process was implemented. In Phase 1, the most relevant concepts for this patient population were selected from existing mental health scales, using data from 79 patients. In Phase 2, an interdisciplinary panel of experts generated scale items. In Phase 3, the scale underwent pre-testing with gastroenterologists (n = 9), health psychologists (n = 3), and patients (n = 12), with feedback incorporated over multiple rounds. Lastly, the psychometric properties of the scale were assessed in a sample of 311 patients via an online survey.ResultsThe AGBW Survey comprises a patient preface, 10 close-ended questions, and an optional open-ended question. This multidimensional scale assesses general mental health, alongside specific subscales relating to depression, stress, and anxiety. The subscale and total scores demonstrated high internal consistency (α = 0.91 for the total scale; α = 0.72–0.86 for subscales) and good convergent, divergent, concurrent validity, and known groups validity, with large effect sizes.ConclusionThe AGBW Survey is a brief, valid, and reliable scale for assessing mental health in patients with chronic gastroduodenal symptoms. It can be used as a tool to complement physiological tests and has the potential to guide psychological referrals, inform multidisciplinary management, and evaluate treatment outcomes.
The relationship between depression and lipid accumulation product: a population-based study
Authors: Zhu Xianlin , Wang Peng , Yue Ya , Wu Tiancheng , Cui Jiali , Shu Yanping , Ma Ling 
Published: July 2024

BackgroundLipid Accumulation Product (LAP) is a new type of obesity index. The relationship between LAP and depression is unclear, and this cross-sectional study was conducted to explore the relationship between LAP and depression using the National Health and Nutrition Examination Survey (NHANES) database from 2005–2018.MethodsIn our study, logistic regression analysis was used to calculate the odds ratio between depression and LAP, and subgroup analysis and sensitivity analysis were also performed to verify the robustness of the results.ResultsThe analysis included 13,240 participants aged 20 years or older. After adjusting for multiple variables, LAP was positively associated with depression, OR 1. 50 (95% CI, 1. 05–2. 12). In subgroup analysis, LAP was significantly positively, associated with depression among male (2. 52, OR; 95% CI, 1. 39,4. 57), non-Hispanic Black (2. 55, OR; 95% CI, 1. 49,4. 36), those without diabetes (1. 67, OR; 95% CI, (1. 06,2. 61) or in the overweight (2. 09, OR; 95% CI, (1. 23,3. 54) subgroups. After inverse probability of treatment weighting (IPTW), the OR for the highest versus lowest quartile was 1. 55 (95% CI: 1. 24 – 1. 95).ConclusionThere are positive results between LAP and depression after adjusting for multiple potential variables, and prospective studies are needed to verify the results.