bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal link between hypothyroidism and gastric cancer risk: insights gained through multivariable Mendelian randomization and mediation analysis
Authors: Zhang Tianyue , Qiao Jie , Wang Yuanyou , Zhou Yinying , Jabbar Abdl Sattar Hamoudi Hammza , Hendi Mhd Alaa Al , Wang Jun 
Published: June 2024

BackgroundGastric cancer (GC) is the third leading cause of cancer death worldwide, and hypothyroidism has been identified as a potential influencing factor. Despite known associations between hypothyroidism and various cancers, the causal link between hypothyroidism and GC and potential mediators of this relationship remains unclear. This study aimed to clarify these relationships using Mendelian randomization (MR).MethodsUtilizing genetic variant information from the FinnGen and MRC Integrative Epidemiology Unit open genome-wide association studies (GWAS) databases, we conducted univariable and multivariable MR analyses to explore the causal relationship between hypothyroidism and GC risk. The analysis was adjusted for confounders such as BMI, smoking status, and alcohol intake, and included mediator MR analysis to examine the role of high cholesterol.ResultsWe identified a significant inverse association between hypothyroidism and GC risk (OR = 0.93, 95% CI= 0.89–0.98, P = 0.003), with no evidence of reverse causation or pleiotropy. Adjustments for Helicobacter pylori infection weakened this association. Mediator analysis highlighted high cholesterol levels, chronic hepatitis B infection, and diabetes/endocrine disease status as significant mediators of the protective effect of hypothyroidism on GC risk.ConclusionOur findings suggest that hypothyroidism may confer a protective effect against GC, mediated in part by high cholesterol and other factors. These results underscore the importance of thyroid function and metabolic health in GC risk, offering new insights for preventive strategies and highlighting the need for further research into these complex associations.
A meta-analysis: elucidating diagnostic thresholds of peak systolic flow velocities in thyroid arteries for the discrimination of Graves’ disease and destructive thyrotoxicosis
Authors: Li Sinong , Ding Zheng , Li Xiang , Fu Miao , Sang Li , Yang Mingxia , Tang Rubo , Gu Tianxiang , Sang Liang 
Published: June 2024

ObjectiveThis meta-analysis examines peak systolic velocities (PSVs) in thyroid arteries as potential biomarkers for thyroid disorders, which includes treated and untreated Graves’ disease(GD) and destructive thyrotoxicosis(DT).MethodsA search across databases including PubMed, Google Scholar, Embase, and Web of Science identified studies assessing peak systolic flow velocity in the inferior thyroid artery (ITA-PSV) and superior thyroid artery (STA-PSV) diagnostic efficacy in GD and DT.And the search was restricted to publications in the English language.The analysis compared STA-PSV and ITA-PSV across patient groups, evaluating intra-group variances and synthesizing sensitivity and specificity data.ResultsThe analysis covered 18 studies with 1276 GD, 564 DT patients, and 544 controls. The difference of STA-PSV between GD group, DT group and normal group and the difference of ITA-PSV were analyzed in subgroups, and there was no statistical significance between subgroups when comparing any two groups. Normal subjects displayed intra-group ITA-PSV and STA-PSV differences with established cut-off values of 20.33 cm/s (95% CI, 17.48-23.18) for ITA-PSV and 25.61 cm/s (95% CI, 20.37-30.85) for STA-PSV. However, no significant intra-group differences were observed in the STA-PSV and ITA-PSV cut-off values among groups with GD or DT. The combined cut-off values for these patient groups and normal subjects were 68.63 cm/s (95% CI, 59.12-78.13), 32.08 cm/s (95% CI, 25.90-38.27), and 23.18 cm/s (95% CI, 20.09-26.28), respectively. The diagnostic odds ratio(DOR) for these values was 35.86 (95% CI, 18.21-70.60), and the area under the summary receiver operating characteristic (SROC) curve was 0.91, with a sensitivity estimate of 0.842 (95% CI, 0.772-0.866).ConclusionPSVs in thyroid arteries are useful diagnostic tools in distinguishing DT from GD. A PSV above 68.63 cm/s significantly improves GD diagnosis with up to 91% efficacy. No notable differences were found between superior and inferior thyroid arteries in these conditions.
Diabetes care and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes in German-speaking countries
Authors: Auzanneau Marie , Reinauer Christina , Ziegler Julian , Golembowski Sven , de Beaufort Carine , Schöttler Hannah , Hahn Eva , Mirza Joaquina , Galler Angela , Wurm Michael , Holl Reinhard W. 
Published: June 2024

IntroductionCurrently, over two million war refugees live in Germany. Exposure to war and flight is associated with a high burden of diseases, not limited to mental disorders and infections. We aimed to analyze diabetes treatment and outcomes of pediatric refugees and migrants from Ukraine and Syria/Afghanistan with type 1 diabetes (T1D) in German-speaking countries.Materials and methodsWe included patients with T1D documented between January 2013 and June 2023 in the German/Austrian/Luxembourgian/Swiss DPV registry, aged &lt; 20 years, born in Ukraine [U], in Syria or Afghanistan [S/A], or without migration background [C]. Using logistic, linear, and negative binomial regression models, we compared diabetes technology use, BMI-SDS, HbA1c values, as well as severe hypoglycemia and DKA rates between groups in the first year of treatment in the host country. Results were adjusted for sex, age, diabetes duration, and time spent in the host country.ResultsAmong all patients with T1D aged &lt; 20 years, 615 were born in Ukraine [U], 624 in Syria or Afghanistan [S/A], and 28,106 had no migration background [C]. Compared to the two other groups, patients from Syria or Afghanistan had a higher adjusted BMI-SDS (0.34 [95%-CI: 0.21–0.48] [S/A] vs. 0.13 [- 0.02–0.27] [U] and 0.20 [0.19–0.21] [C]; all p&lt;0.001), a lower use of CGM or AID system (57.6% and 4.6%, respectively [S/A] vs. 83.7% and 7.8% [U], and 87.7% and 21.8% [C], all p&lt;0.05) and a higher rate of severe hypoglycemia (15.3/100 PY [S/A] vs. 7.6/100 PY [C], and vs. 4.8/100 PY [U], all p&lt;0.05). Compared to the two other groups, patients from Ukraine had a lower adjusted HbA1c (6.96% [95%-CI: 6.77–7.14] [U] vs. 7.49% [7.32–7.66] [S/A] and 7.37% [7.36–7.39] [C], all p&lt;0.001).DiscussionIn their first treatment year in the host country, young Syrian or Afghan refugees had higher BMI-SDS, lower use of diabetes technology, higher HbA1c, and a higher rate of severe hypoglycemia compared to young Ukrainian refugees. Diabetologists should be aware of the different cultural and socioeconomic backgrounds of refugees to adapt diabetes treatment and education to specific needs.
Non-diabetic elderly populations: the MHR as a protective factor against bone abnormalities
Authors: Li Xiang , Yan Manli , Ji Jiali , Ma Zhuohao 
Published: June 2024

ObjectivesIn China, osteoporosis has become a major health concern among elderly population, imposing significant burden on the country’s social and economic systems. The monocyte to high-density lipoprotein ratio (MHR) has been currently recommended as a novel marker of inflammation and oxidative stress associated with osteoporosis in type 2 diabetes mellitus (T2DM). However, its reliability in non-diabetic elderly populations remains unclear. The present study was to evaluate the association between MHR and osteoporosis in a non-diabetic elderly population.MethodsThe clinical data of 240 non-diabetic elderly subjects (115 in the osteoporosis group and 125 in the normal bone group) were retrospectively analyzed and all statistical analyses were performed by using SPSS 26.0.ResultsDifferences in age, neutrophils, lymphocytes, monocytes, MHR, uric acid, creatinine, triglycerides,and high-density lipoprotein cholesterol were found to be statistically significant between the two groups. A binary logistic regression model was conducted by including age, MHR, UA and Cr as variables. The results showed that age was an independent risk factor and MHR was an independent protective factor for bone abnormality in the non-diabetic elderly population. The ROC analysis showed that the area under the curve for the predictive effect of MHR, age and their combined test on osteoporosis in non-diabetic elderly populations was 0.623, 0.728 and 0.761, respectively; the correlation analysis showed that MHR was positively correlated with lumbar and hip BMD, and negatively associated with femoral neck stress ratio, femoral intertrochanteric stress ratio, and femoral stem stress ratio, showing statistically significant differences (P&lt;0.05).ConclusionsFor the non-diabetic elderly population: the MHR is a protective factor against bone abnormalities and was significantly higher in the normal bone group than in the abnormal bone group.
Construction of a 3-year risk prediction model for developing diabetes in patients with pre-diabetes
Authors: Yang Jianshu , Liu Dan , Du Qiaoqiao , Zhu Jing , Lu Li , Wu Zhengyan , Zhang Daiyi , Ji Xiaodong , Zheng Xiang 
Published: June 2024

IntroductionTo analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM.MethodsSubjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted.ResultsComparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P&lt;0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P&gt;0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P&lt;0.05), while HDL-C was a protective factor (P&lt;0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model.ConclusionsThe risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration.
Genetic Landscape of SH3TC2 variants in Russian patients with Charcot–Marie–Tooth disease
Authors: Shchagina Olga , Murtazina Aysylu , Chausova Polina , Orlova Mariya , Dadali Elena , Kurbatov Sergei , Kutsev Sergey , Polyakov Aleksander 
Published: June 2024

Introduction:Charcot–Marie–Tooth disease type 4C (CMT4C) OMIM#601596 stands out as one of the most prevalent forms of recessive motor sensory neuropathy worldwide. This disorder results from biallelic pathogenic variants in the SH3TC2 gene.Methods:Within a cohort comprising 700 unrelated Russian patients diagnosed with Charcot–Marie–Tooth disease, we conducted a gene panel analysis encompassing 21 genes associated with hereditary neuropathies. Among the cohort, 394 individuals exhibited demyelinating motor and sensory neuropathy.Results and discussion:Notably, 10 cases of CMT4C were identified within this cohort. The prevalence of CMT4C among Russian demyelinating CMT patients lacking the PMP22 duplication is estimated at 2.5%, significantly differing from observations in European populations. In total, 4 novel and 9 previously reported variants in the SH3TC2 gene were identified. No accumulation of a major variant was detected. Three previously reported variants, c.2860C&gt;T p. (Arg954*), p. (Arg658Cys) and c.279G&gt;A p. (Lys93Lys), recurrently detected in unrelated families. Nucleotide alteration p. (Arg954*) is present in most of our patients (30%).
Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer
Authors: Kuang Zhanpeng , Miao Jessica , Zhang Xiaoli 
Published: June 2024

BackgroundImmune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy.MethodsOur study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy.ResultsLogistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20–2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P&lt;.0001, HR 0.33, 95% CI: 0.20–0.55) and the metastatic cohort (P&lt;.0001, HR 0.28, 95% CI: 0.15–0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P&lt;.0001).ConclusionOur data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.
Proof of concept of a new plasma complement Factor H from waste plasma fraction
Authors: Mori Filippo , Pascali Giancarlo , Berra Silvia , Lazzarotti Alessandra , Panetta Daniele , Rocchiccioli Silvia , Ceccherini Elisa , Norelli Francesco , Morlando Antonio , Donadelli Roberta , Clivio Alberto , Farina Claudio , Noris Marina , Salvadori Piero A. , Remuzzi Giuseppe 
Published: June 2024

IntroductionComplement factor H (FH) is a major regulator of the complement alternative pathway, its mutations predispose to an uncontrolled activation in the kidney and on blood cells and to secondary C3 deficiency. Plasma exchange has been used to correct for FH deficiency and although the therapeutic potential of purified FH has been suggested by in vivo experiments in animal models, a clinical approved FH concentrate is not yet available. We aimed to develop a purification process of FH from a waste fraction rather than whole plasma allowing a more efficient and ethical use of blood and plasma donations.MethodsWaste fractions from industrial plasma fractionation (pooled human plasma) were analyzed for FH content by ELISA. FH was purified from unused fraction III and its decay acceleration, cofactor, and C3 binding capacity were characterized in vitro. Biodistribution was assessed by high-resolution dynamic PET imaging. Finally, the efficacy of the purified FH preparation was tested in the mouse model of C3 glomerulopathy (Cfh−/− mice).ResultsOur purification method resulted in a high yield of highly purified (92,07%), pathogen-safe FH. FH concentrate is intact and fully functional as demonstrated by in vitro functional assays. The biodistribution revealed lower renal and liver clearance of human FH in Cfh-/- mice than in wt mice. Treatment of Cfh-/- mice documented its efficacy in limiting C3 activation and promoting the clearance of C3 glomerular deposits.ConclusionWe developed an efficient and economical system for purifying intact and functional FH, starting from waste material of industrial plasma fractionation. The FH concentrate could therefore constitute possible treatments options of patients with C3 glomerulopathy, particularly for those with FH deficiency, but also for patients with other diseases associated with alternative pathway activation.
Neointimal hyperplasia after endoluminal injury in mice is dependent on tissue factor- and angiopoietin-2 dependent interferon gamma production by fibrocytes and macrophages
Authors: Chen Daxin , Li Ke , Wei Lin-Lin , Ma Ning , McVey John H. , Dorling Anthony 
Published: June 2024

BackgroundThe intimal hyperplasia (IH) and vascular remodelling that follows endovascular injury, for instance after post-angioplasty re-stenosis, results in downstream ischaemia and progressive end organ damage. Interferon gamma (IFNγ) is known to play a critical role in this process. In mouse models we have previously shown that fibrocytes expressing tissue factor (TF) are recruited early to the site of injury. Through thrombin generation and protease activated receptor-1 (PAR-1) activation, fibrocytes secrete angiopoietin-2, stimulate neointimal cell proliferation, inhibit apoptosis and induce CXCL-12 production, all of which contribute to the progressive IH that then develops. In this study we investigated the relationship between TF, angiopoietin-2 and IFNγ.Methods and resultsIH developing in carotid arteries of wild-type mice 4 weeks after endoluminal injury contained a significant proportion of IFNγ+ fibrocytes and macrophages, which we show, using a previously defined adoptive transfer model, were derived from circulating CD34+ cells. IH did not develop after injury in IFNγ-deficient mice, except after transplantation of WT bone marrow or adoptive transfer of WT CD34+ cells. In vitro, CD34+ cells isolated from post-injury mice did not express IFNγ, but this was induced when provided with FVIIa and FX, and enhanced when prothrombin was also provided: In both cases IFNγ secretion was TF-dependent and mediated mainly through protease activated PAR-1. IFNγ was predominantly expressed by fibrocytes. In vivo, all IFNγ+ neointimal cells in WT mice co-expressed angiopoietin-2, as did the small numbers of neointimal cells recruited in IFNγ-/- mice. Adoptively transferred WT CD34+ cells treated with either an anti-TIE-2 antibody, or with siRNA against angiopoetin-2 inhibited the expression of IFNγ and the development of IH.ConclusionTF-dependent angiopoietin-2 production by newly recruited fibrocytes, and to a lesser extent macrophages, switches on IFNγ expression, and this is necessary for the IH to develop. These novel findings enhance our understanding of the pathophysiology of IH and expose potential targets for therapeutic intervention.
Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study
Authors: Valdes Ana M. , Ikram Adeel , Taylor Lauren A. , Zheng Amy , Kouraki Afroditi , Kelly Anthony , Ashraf Waheed , Vijay Amrita , Miller Suzanne , Nightingale Jessica , Selby Nicholas M. , Ollivere Benjamin J. 
Published: June 2024

BackgroundHip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.MethodsIn a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers.ResultsOf the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76–40.51], and with both markers plus estimated glomerular filtration rate (eGFR)– cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI.ConclusionHigh postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.