bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum-derived small extracellular vesicles as biomarkers for predicting pregnancy and delivery on assisted reproductive technology in patients with endometriosis
Authors: Muraoka Ayako , Yokoi Akira , Yoshida Kosuke , Kitagawa Masami , Bayasula  , Murakami Mayuko , Miyake Natsuki , Sonehara Reina , Nakamura Tomoko , Osuka Satoko , Kajiyama Hiroaki 
Published: January 2025

IntroductionEndometriosis can cause of infertility, and evaluation methods for predicting clinical pregnancy outcomes are desired. Extracellular vesicles (EVs) exist in blood and it contains small non-coding RNAs (ncRNAs) that may reflect disease severity. In this study, we investigated small ncRNAs in serum EVs to identify specific biomarkers for predicting clinical pregnancy.MethodsSerum samples were collected from 48 patients who underwent assisted reproductive technology (ART). EVs were successfully isolated from serum samples and characterized using nanoparticle tracking assays, electron microscopy, and western blotting of EV’s markers. We performed small RNA sequencing and analyzed microRNA (miRNA) profiles in the infertility patients with and without endometriosis to detect pregnancy-predicting biomarkers.ResultsCandidate miRNAs in serum EVs were selected by comparing patients without endometriosis who became pregnant (n = 13) with those who did not (n = 21). A total of 241 miRNAs were detected; however, no trends separated the two groups. Next, EVs from patients with endometriosis were analyzed and divided into pregnant (n = 4) and non-pregnant (n = 10) cases. Among the 224 candidate miRNAs, miRNA profiles of pregnant women with endometriosis were separated from those of non-pregnant women by receiver-operating characteristics (ROC) curve analysis (area under the curve [AUC] &gt; 0.8). In patients with endometriosis, serum EVs may be useful for predicting possible pregnancy before infertility treatment. Finally, we used small RNA sequencing of the tissue to demonstrate that pregnancy-predicting miRNAs in serum EVs were produced from endometriosis lesions. Although no predictors were found from miRNAs in serum EVs without endometriosis, miRNAs in serum EVs of patients with endometriosis could provide novel noninvasive biomarkers to predict pregnancy and have potential clinical applicability in ART.DiscussionFurther studies are required to examine the functional importance of these miRNAs to elucidate the pathological mechanisms of endometriosis and pregnancy.
Causal relationship between 412 gut microbiota, 1,400 blood metabolites, and diabetic nephropathy: a randomized Mendelian study
Authors: Cao Bo-Ning , Zhang Cai-Yan , Wang Zhen , Wang Yao-Xian 
Published: January 2025

ObjectiveThe aim of this study was to investigate the causal relationship between microbiota, diabetic nephropathy, and blood metabolites through a randomized Mendelian study.MethodsIn this study, we used 412 microbiota as exposures, 1,400 blood metabolites as intermediaries, and diabetic nephropathy as the outcome. We conducted a two-way Mendelian randomization (MR) analysis to explore the causal relationship between microbiota and diabetic nephropathy, followed by mediation analyses and two-step MR to identify potential blood metabolites.ResultsThere is a causal relationship between microbiota and diabetic nephropathy. Specific bacteria and metabolites, such as Escherichia coli str. K-12 substr. MG1655, Listeria monocytogenes 10403S, g_Adlercreutzia, g_Haemophilus, g_Bacteroides, and Escherichia coli CFT073, and metabolites like pyrraline, glycocholenate sulfate, alpha-ketoglutarate, tetradecadienoate (14:2), Cys-gly oxidized, methylsuccinate, and various others, were identified. Escherichia coli str. K-12 substr. MG1655 is positively related to alpha-ketoglutarate levels, while alpha-ketoglutarate levels and Sphingomyelin (d18:1/18:1, d18:2/18:0) are negatively related. The bacterial microbiota involved in fatty acid oxidation is associated with diabetic kidney disease (DKD) progression, positively correlated with glycocholenate sulfate levels, and negatively correlated with the phosphate linoleyl-tetraenyl-glycerol (18:2 to 20:4) ratio. Additionally, Listeria monocytogenes 10403S is positively correlated with N-acetyl-isoputreanine and negatively correlated with X-12462. Anaerobic fermentation-related bacteria were positively related to N-acetylcarnitine and 5-acetylamino-6-formyluracil and negatively correlated with 5-acetamino-6-amino-3-methyluracil (X-24243). Escherichia coli CFT073 was positively associated with X-16580. Interactions between Bacillus species and metabolites such as d18:1/18:1, d18:2/18:0, 2-aminophenol sulfate, and cholate were negative when compared to tetradecadienoate (14:2). g_Adlercreutzia is positively correlated with N-delta-acetylornithine, methylsuccinate, and N-acetyl-isoputreanine but negatively correlated with N-acetylglucosamine and N-acetylgalactosamine. g_Haemophilus was positively associated with arachidoylcarnitine but negatively correlated with X-24531. The results were heterogeneous and multi-efficacious.ConclusionsFor the first time, MR analysis provides supportive evidence for a bidirectional causal relationship between microbiota and diabetic nephropathy and identifies specific genes associated with the disease. The results suggest that probiotic therapy may play a significant role in preventing diabetic nephropathy and improving the quality of life and survival rates of affected patients. Furthermore, this study provides additional evidence of a causal relationship between specific microbiota, diabetic nephropathy, and blood metabolites.
Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation
Authors: Zhang Meng , Zhang Xiaomei , Wang Jiaxi , Lu Wenyi , Xiao Xia , Lyu Hairong , He Xiaoyuan , Pu Yedi , Meng Juanxia , Lyu Cuicui , Cao Xinping , Zhao Mingfeng 
Published: January 2025

BackgroundHuman C-type lectin-like molecule 1 (CLL-1) represents a promising therapeutic target for Chimeric antigen receptor T (CAR-T) cells therapy in the treatment of acute myeloid leukemia (AML). In this study, we aimed to evaluate the efficacy and safety profile of donor-derived CLL-1 CAR-T cells in AML patients who experienced relapsed post-transplantation.Methods14 AML patients who experienced relapse following allogeneic HSCT were enrolled in our clinical trial. However, 2 patients withdrew from the study due to rapid disease progression. 12 participants received donor-derived CLL-1 CAR-T cells and were categorized into 3 groups based on the dosage of infused CAR-T cells dose (Group A:0.5×106/kg, Group B:1×106/kg, Group C:1.5×106/kg). And scRNA-seq was used to reveal CLL-1 CAR-T cells dynamics in a CAR-T cells infusion products and PBMCs at the peak of expansion for patient 4.ResultsCLL-1 CAR-T cells were well tolerated by all 12 patients. Cytokine Release Syndrome (CRS) was observed in all patients, with 5 patients experiencing grade ≥3. 3 patients developed cytokine release syndrome-associated encephalopathy (CRES), and 1 patient had a grade 4 severity level. All patients demonstrated a reduction in tumor burden, while 7 patients (58.33%) achieved MRD-CR and 2 patients (16.67%) reached MRD+CR. CAR-T cells expansion was detectable in all 12 patients, with the median time of peak expansion was 9 days (range: 7-11 days). In patient 4, compared to the pre-reinfusion state, CD4+ cells at the peak of expansion showed upregulation of cell killing-related genes and memory T cell-related genes (P &lt; 0.01).ConclusionsThe CLL-1 CAR-T cells therapy derived from allogeneic donors demonstrates both safety and efficacy in the management of relapsed AML following allogeneic HSCT. And adjusting the ratio of CD4+ CAR-T cells and CD8+ CAR-T cells prior to infusion may help mitigate CAR-T cell-related side effects.Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000041054.
Diagnostic performance of multi-branch coronary angiography-based index of microcirculatory resistance: a novel approach
Authors: Fan Yongzhen , Wang Shuang , Cai Xinyong , Lu Zhibing , Ma Jun , Lan Hongzhi , Hu Xiaorong 
Published: January 2025

BackgroundWire-based index of microcirculatory resistance (IMR) utilizing pressure wires and thermodilution techniques for the assessment of coronary microcirculatory function, presents challenges for clinical routine use due to its complexity, time-consuming, and costly. This study introduces a novel multi-branch and wire-free method for IMR calculation based on coronary angiography. The diagnostic performance of CAG-IMR is validated within a retrospective single-center investigation.MethodsIn a retrospective single-center study, 139 patients with 201 vessels were evaluated using CAG-IMR for coronary microvascular dysfunction (CMD) detection, utilizing wire-based IMR as the reference standard. CMD was determined based on wire-based IMR ≥25U. CAG-IMR was independently calculated from diagnostic coronary angiography in a blinded fashion, employing the same diagnostic threshold of 25U for CMD identification.ResultsCAG-IMR demonstrated significant correlation (r = 0.84, p &lt; 0.001) and good diagnostic performance AUC = 0.97 (95% CI: 0.95–0.99) compared to wire-based IMR. It exhibited the overall diagnostic accuracy at 95.0% (95% CI: 92.0%−98.0%), alongside high sensitivity (92.7%) and specificity (95.6%). The positive predictive value (PPV) stood at 84.4%, and the negative predictive value (NPV) reached 98.1%.ConclusionsThis study introduces CAG-IMR, a novel, multi-branch and wire-free method for IMR calculation. The indicator demonstrates good diagnostic accuracy and correlation with wire-based IMR in a cohort of 139 patients and 201 vessels, with the potential to enhance clinical CMD assessment.
Impairment of neuronal activity in the dorsolateral prefrontal cortex occurs early in parkinsonism
Authors: Hjelle Noah , Mohanty Biswaranjan , Hubbard Tanner , Johnson Matthew D. , Wang Jing , Johnson Luke A. , Vitek Jerrold L. 
Published: January 2025

BackgroundParkinson’s disease (PD) is often characterized by altered rates and patterns of neuronal activity in the sensorimotor regions of the basal ganglia thalamocortical network. Little is known, however, regarding how neuronal activity in the executive control network of the brain changes in the parkinsonian condition.ObjectiveInvestigate the impact of parkinsonism on neuronal activity in the dorsolateral prefrontal cortex (DLPFC), a key region in executive control, during a go/nogo reaching task.MethodsUsing a within-subject design, single and multi-unit neuronal activity was recorded in the DLPFC of a nonhuman primate (n = 1) before and after the induction of mild parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).ResultsCoincident with development of mild parkinsonian motor signs, there was a marked reduction in the percentage of DLPFC cells with significant task-related firing rate modulation during go and nogo conditions.ConclusionThese results suggest that DLPFC dysfunction may occur early in parkinsonism and contribute to cognitive impairments and disrupted executive function often observed in PD patients.
Association between oxidative balance scores and peripheral artery disease in US adults: a cross-sectional study
Authors: Zhou Min , He Peng-Fei , Zhang Keren , Deng Li-Juan , Wang Ning , Wang Gang , Yang Guang-Yao , Ju Shang 
Published: January 2025

BackgroundThe Oxidative Balance Score (OBS) quantifies the overall oxidative stress burden, with higher scores indicating greater antioxidant (relative to prooxidant) activity. This study aimed to examine the association between peripheral arterial disease (PAD) and OBS.Methods and materialsData from the National Health and Nutrition Examination Survey (NHANES, 1999–2004) were analyzed for participants with ankle-brachial index (ABI) measurements. The total Oxidative Balance Score (OBS) comprised a lifestyle OBS (four lifestyle categories) and a dietary OBS (16 dietary factors). Logistic regression analyses evaluated associations between PAD and total OBS, lifestyle OBS, and dietary OBS. Restricted cubic spline (RCS) analyses assessed dose–response relationships between ABI, PAD, and OBS. Mediation analyses investigated the roles of glucolipid metabolism and renal function in the OBS-PAD association. Sensitivity and stratification analyses were conducted to ensure robustness.ResultsThis study included 2,437 eligible adult participants. Logistic regression analysis, adjusted for multiple potential confounders, revealed negative associations between lifestyle OBS (OR = 0.88; 95% CI: 0.79, 1.00), total OBS (OR = 0.97; 95% CI: 0.94, 0.99), and the likelihood of PAD (all p &lt; 0.05). Restricted cubic spline (RCS) analysis demonstrated a linear relationship between total OBS and PAD, with the likelihood of PAD decreasing as total OBS increased p for nonlinearity = 0.736. Dietary OBS, lifestyle OBS, and total OBS all showed positive linear correlations with ABI levels (all p &lt; 0.05). Mediation analysis indicated that fasting plasma glucose (FPG) and creatinine (CREA) mediated 5.9 and 0.8% of the association between total OBS and PAD, respectively (all p &lt; 0.05). Sensitivity analyses confirmed the negative association between total OBS and PAD p &lt; 0.05, supporting the stability of the results. Stratified analyses highlighted the significant influence of Age, particularly in the younger population aged 20–44 years, a group warranting greater attention.ConclusionOur study demonstrated that higher total OBS is associated with a lower likelihood of PAD. Adopting an antioxidant-rich diet alongside a healthy lifestyle may help mitigate PAD risk. Additionally, modulating FPG and CREA levels could offer potential value in addressing the link between low OBS and PAD.
Association of the newly proposed dietary index for gut microbiota and constipation: a cross-sectional study from NHANES
Authors: Zhang Zhuhui , Bi Chunlu , Wu Runsheng , Qu Muwen 
Published: January 2025

ObjectiveThe dietary index for gut microbiota. DI-GM is an innovative metric designed to capture the diversity of the gut microbiome, yet its association with constipation remains unstudied.MethodsIn this cross-sectional study, 11,405 adults aged 20 and older were selected from the National Health and Nutrition Examination Survey 2005–2010 for the sample. Constipation was defined as fewer than three defecation frequencies per week using bowel health questionnaire (BHQ). Fewer than three bowel movements per week were considered as constipation by Bowel Health Questionnaire (BHQ). DI-GM was derived from dietary recall data, including avocado, broccoli, chickpeas, coffee, cranberries, fermented dairy, fiber, green tea, soybean and whole grains as beneficial elements, red meat, processed meat, refined grains, and high fat as detrimental components. Multivariable weighted logistic was employed to investigate the association of DI-GM with constipation. Secondary analyses included subgroup analyses, restricted cubic spline (RCS), and multiple imputation.ResultsA higher DI-GM and beneficial gut microbiota score were associated with a lower prevalence of constipation (DI-GM: OR = 0.82, 95% CI = 0.75, 0.90; beneficial gut microbiota score: OR = 0.77, 95% CI = 0.67, 0.89). After grouping DI-GM, in the fully adjusted model, participants with DI-GM ≥ 6 were significantly negatively correlated with both the prevalence of constipation (OR = 0.48, 95% CI = 0.33, 0.71). RCS indicated a non-linear relationship between DI-GM and constipation. Subgroup analyses by age, sex and common complications showed no statistically significant interactions (p &gt; 0.05).ConclusionThe newly proposed DI-GM was inversely related with the prevalence of constipation. When treating patients with constipation, it is necessary for clinicians to provide timely and effective dietary interventions incorporating the DI-GM for patients with constipation to avoid further deterioration of the condition.
Maternal prepregnancy overweight/obesity increase the risk of low Apgar scores in twins: a population-based cohort study in China
Authors: Feng Zhoushan , Wu Xiaohong , Tong Xiaomei , He Zheng , Yang Chunxia , Shen Wei , Ding Yueqin , Liu Jin , Meng Qiong , Zhang Aiqin , Jiang Hong , Yan Wenkang , Qiu Jianwu , Wei Xian , Zhang Yayu , Lin Xiaobo , Liu Lijun , Jin Ya , Wei Youfen , Yang Xiufang , Wang Yitong , Cai Yangfan , Lin Xinzhu , Cui Qiliang 
Published: January 2025

ObjectiveWhile prepregnancy overweight or obesity is known to negatively impact maternal health, its effect on twin infants is not well understood. Therefore, we conducted a nationwide, multicenter retrospective study to investigate the association between maternal prepregnancy weight and health outcomes in twins.Study designThis study collected data from 22 healthcare units across 12 regions in China between January 2018 and December 2020. To control for confounding factors, multiple logistic regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlapping weighting models (OW) were applied to explore the effects of prepregnancy BMI on Apgar scores and other outcomes.ResultsAfter screening, a total of 4,724 women with twin pregnancies and 9,448 newborns were included in the study. Compared to normal prepregnancy weight, prepregnancy overweight/obesity significantly increased the risk of gestational hypertension and gestational diabetes in mothers [adjusted OR (95% CI): 1.85 (1.55–2.21) and 1.49 (1.27–1.74), respectively]. It also increased the incidence of twins with a 1-min Apgar score ≤7, whether they were larger or smaller [1.60 (1.20–2.13) and 1.45 (1.09–1.92), respectively]. Sensitivity analyses using PSM [1.60 (1.20–2.13) and 1.55 (1.07–2.25)], IPTW [1.67 (1.31–2.12) and 1.48 (1.17–1.87)], and OW [1.65 (1.08–2.57) and 1.47 (0.97–2.25)] confirmed the stability of these results. However, it did not affect the likelihood of a 5-min Apgar score ≤7 [adjusted OR (95% CI): 0.82 (0.24–2.17) and 1.40 (0.70–2.73)]. In contrast, prepregnancy underweight was associated with a reduced incidence of twins with a 1-min Apgar score ≤7 [adjusted OR (95% CI): 0.56 (0.32–0.92) and 0.58 (0.34–0.94)], but had no effect on the 5-min Apgar score ≤7 [adjusted OR (95% CI): 0.82 (0.24–2.17) and 0.22 (0.01–1.08)]. Prepregnancy BMI did not significantly affect twin birth weight discordance, NICU admission, preterm birth, or low birth weight.ConclusionMaternal overweight/obesity before pregnancy increases the risk of hypertensive disorders and gestational diabetes in twin pregnancies and significantly raises the likelihood of twins having a low 1-min Apgar score. However, no significant impact on 5-min Apgar scores was observed. These findings highlight the importance of managing weight before pregnancy and ensuring readiness for neonatal resuscitation during delivery.
Lung ultrasound to evaluate the outcome and prognosis of transient tachypnea of the newborn
Authors: Jiang Peng , Wei Jing , Han Meiying 
Published: January 2025

Background/ObjectivesTransient tachypnea of the newborn (TTN) is generally self-limiting. The increasing incidence of severe cases and lack of comprehensive studies on its clinical outcomes and influencing factors highlight the need for improved diagnostic and monitoring tools. This study aimed to assess the lung ultrasonographic features, recovery durations, and factors influencing TTN.MethodsTwo hundred neonates with wet lungs were selected as the TTN group and divided into mild (132/200) and severe (68/200) groups. Two hundred neonates without pulmonary disease served as controls. The acute-phase lung ultrasonographic features of the two groups were compared. According to the clinical recovery duration, TTN group was divided into group A (&lt;5 days, 191/200) and group B (≥5 days, 9/200). Univariate and multivariate logistic regression analyses were used to analyze the relationship between clinically relevant factors and the recovery time.ResultsThe time that was required for the 200 neonates to fully recover without symptoms was 2.3 ± 1.33 days. The average clinical recovery durations of neonates with mild illness, those who required non-invasive ventilation, and those who required invasive ventilation were 1.42 ± 0.50, 3.36 ± 0.51, and 6.00 ± 1.12 days, respectively. The differences between the groups were significant (P &lt; 0.05). Type II respiratory failure, acute respiratory distress syndrome (ARDS), persistent pulmonary hypertension of the newborn (PPHN), and heart failure were important factors affecting the recovery time.ConclusionThe lung ultrasonographic signs differed based on the degree of wet lungs. Moreover, type II respiratory failure, ARDS, PPHN, and heart failure are important factors prolonging the course of TTN in neonates.
Elocalcitol, a fluorinated vitamin D derivative, prevents high-fat diet-induced obesity via SCAP downregulation and miR-146a-associated mechanisms
Authors: Jürgenson Monika , Chithanathan Keerthana , Orav Aivar , Jaako Külli , Viil Janeli , Guha Mithu , Kask Kalev , Zharkovsky Alexander 
Published: January 2025

BackgroundObesity is an emerging health problem worldwide as it is associated with increased risk of cardiovascular, metabolic, mental disorders, and cancer. Therapeutic weight management remains one of the options for the treatment of excess weight and associated comorbidities. In this study, the therapeutic potential of elocalcitol, a fluorinated derivative of vitamin D, was studied on the model of high-fat diet (HFD)-induced obesity in mice.ResultsIt was demonstrated that co-administration of elocalcitol in the doses 15 ug/kg (i.p.) twice a week for 16 weeks prevented body weight gain by approximately 15%. The significant retardation in the body weight gain was observed already on the second week of elocalcitol treatment. Administration of elocalcitol also reduced visceral and epididymal fat accumulation by 55% and 35%, respectively, metabolic syndrome development, and lipid droplets accumulation in the liver of mice exposed to HFD. In contrast, the administration of cholecalciferol (vitamin D)—a precursor to calcitriol, the biologically active form of vitamin D, did not affect significantly the signs of obesity and metabolic syndrome, suggesting that the anti-obese effects of elocalcitol are not related to the canonical vitamin D receptor (VDR). Further studies have demonstrated that the preventive effect of elocalcitol is associated with the decreased levels of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and upregulation insulin-inducing gene-1 (Insig1) mRNA expression suggesting that the anti-obese effect of elocalcitol is mediated via inhibition of SREBP-mediated lipogenesis. We also demonstrated that elocalcitol prevents an increase in the expression of proinflammatory cytokines such as interleukin-1 beta (Il1b), tumor necrosis factor-alpha (Tnf), and interleukin-18 (Il18), and this effect was associated with upregulation of microRNA-146a (miR-146a). Deletion of the miR-146a gene reduced the anti-obese effects of elocalcitol and prevented its actions on the SCAP levels. The data indicate that elocalcitol’s reduction of SCAP is at least partly mediated by miR-146a modulation.ConclusionThe study demonstrates that elocalcitol prevents HFD-induced obesity and metabolic syndrome in mice, likely by inhibiting SREBP-mediated lipogenesis and upregulating miR-146a. These findings provide valuable insights into the anti-obesity mechanisms of fluorinated D-vitamin analogs and suggest potential therapeutic strategies for obesity prevention.