bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human umbilical cord mesenchymal stem cells restores mTOR-mediated autophagy homeostasis to alleviate placental injury and improve pregnancy outcomes in preeclampsia
Authors: Xu Miao , Ma Huijing , Chen Yuwen , Zhang Xinhuan , Li Mengnan , Yu Hong , Ji Jing , Li Juanwen , Zhang Nan , Wang Fang , Hao Huiniu , Li Lu , Ruidan Zhang , Chen Yinmin , Yang Lijun , Hao Zhuanghui , Song Huifang , HE SHENG , Yang Hailan 
Published: October 2024

Abstract

Background
Preeclampsia is a hypertensive disorder during pregnancy, which seriously threatens both maternal and infant health. Currently, the only treatment available is to induce infant and placenta delivery, resulting in interest in potential fetal-safe treatment strategies. One such strategy is cell therapy with human umbilical cord mesenchymal stem cells (hUC-MSCs), which possesses immunomodulatory, anti-inflammatory and angiogenic functions that could alleviate pre-eclamptic symptoms. However, the precise effects and underlying mechanisms behind their activities are still largely unknown. In this study, we aimed to elucidate the effect of hUC-MSCs, as well as the pathways involved, on placental function in preeclampsia, thereby highlighting potential novel avenue for stem cell therapy.
Methods
Both an in vivo rat model, involving N-nitro-L-arginine methyl ester (L-NAME) injections in pregnant rats, and an in vitro model, entailing HTR8 trophoblasts/human umbilical cord vein endothelial cells (HUVECs) being stimulated with lipopolysaccharide (LPS), were established to simulate pre-eclampsia. In vivo, maternal blood pressure, renal function, as well as placental and fetal weights, were measured. ELISA was used to measure maternal serum levels of angiogenic, inflammatory, and oxidative stress factors. Placental mitochondrial morphology was evaluated using transmission electron microscopy, while autophagic pathways were analyzed by Western blots. With the in vitro model, cell proliferation, invasion, oxidative stress, and apoptosis were evaluated in a Transwell co-cultured with hUC-MSCs.
Results
hUC-MSC administration was found in the in vivo model to increase fetal weights, along with alleviating hypertension and proteinuria, which are owed to those cells promoting placental angiogenesis and blood perfusion, as well as lowering inflammation, oxidative stress, and apoptosis. These findings were further supported by the in vitro model, where hUC-MSC co-culture with LPS-treated HTR8/HUVECs resulted in increased cell proliferation and invasion, along with lowered apoptosis and reactive oxygen species generation. All of these effects are owed to hUC-MSCs improving placental mitochondrial function by lowering autophagy; this is through activating Akt/mTOR and inhibiting AMPK/mTOR pathways, leading to pro-autophagic LC3 and Beclin1 downregulation, as well as anti-autophagic P62 upregulation.
Conclusion
hUC-MSCs are able to alleviate pre-eclampsia by restoring physiological placental autophagic homeostasis, which could serve as a promising therapeutic strategy for the disease.
Successful treatment of an anti-MDA5 antibody-positive Juvenile Dermatomyositis patient with refractory interstitial lung disease using tofacitinib
Authors: Natoli Valentina , Palmeri Serena , Rebollo-Giménez Ana Isabel , Matucci-Cerinic Caterina , Bocca Paola , Caorsi Roberta , Volpi Stefano , Papa Riccardo , Consolaro Alessandro , Gattorno Marco , Ravelli Angelo , Rosina Silvia 
Published: October 2024

Abstract

Juvenile dermatomyositis (JDM) is a rare autoimmune disorder affecting children, mainly characterized by skin rash and muscle weakness (1). Anti-MDA5 antibody-positive JDM represents a distinct phenotype of disease with a high risk of developing life-threatening progressive interstitial lung disease (ILD)(2). The pivotal role of the type I interferon (IFN) pathway in the pathogenesis of anti-MDA5 positive JDM has prompted the exploration of Janus kinase (JAK) inhibitors as a therapeutic option (3). Nevertheless, while the efficacy and safety of JAK inhibitors have been established in clinical trials including adult-onset anti-MDA5-antibody positive DM (4), evidence in paediatric cases with progressive or refractory ILD is limited. In this report we describe the efficacy and safety of tofacitinib, a JAK 1/3 inhibitor, in treating an anti-MDA5-positive JDM young girl with refractory ILD, highlighting the potential of JAK inhibitors as targeted therapy in these patients.
Detection of Low-Frequency Artemisinin Resistance Mutations C469Y, P553L and A675V in Asymptomatic Primary School Children in Kenya
Authors: Osoti Victor , Wamae Kevin , Ndwiga Leonard , Gichuki Paul .M. , Okoyo Collins , Kepha Stella , Keitany Kibor , Kandie Regina , Aricha Stephen , Kiplagat Rosebella , Mwandawiro Charles , Bejon Philip , Snow Robert W. , Ochola-Oyier Lynette Isabella 
Published: October 2024

Abstract

Background: To understand the emergence and spread of drug-resistant parasites in malaria-endemic areas, accurate assessment and monitoring of antimalarial drug resistance markers is critical. Recent advances in next-generation sequencing (NGS) technologies have enabled the tracking of drug-resistant malaria parasites.
Methods: In this study, we used Targeted Amplicon Deep Sequencing (TADs) to characterise the genetic diversity of the Pfk13,Pfdhfr, Pfdhps, and Pfmdr1genes among primary school-going children in 15 counties in Kenya (Bungoma, Busia, Homa Bay, Migori, Kakamega, Kilifi, Kirinyaga, Kisii, Kisumu, Kwale, Siaya, Tana River, Turkana, Vihiga, and West Pokot,). A total of 920 dried blood spot (DBS) samples collected from 121 selected primary schools within the country were used to extract genomic DNA. A nested polymerase chain reaction (PCR) was used to generate amplicons that were sequenced to determine the prevalence of known and novel polymorphisms.
Results:The analysis of Pfk13 mutations associated with artemisinin resistance showed that the C469Y mutation was found in 23 samples (4%), the A675V mutation was identified in 2 samples (1.7%), and the P553L mutation was present as a mixed genotype in 7 samples (1.2%), all as mixed infections. The A578S mutation, one of the most common nonsynonymous mutations found in Africa, was also identified in mixed infections, appearing in 15.2% of the 87 samples analysed. The Pfdhfr 51I and 108N pyrimethamine-resistance mutations were at fixation (100% frequency), and the Pfmdr1 Y184F mutation that has been associated with reduced susceptibility to lumefantrine was found in 97.5% of the samples as mixed genotype infections.
Conclusion:The genomics surveillance of asymptomatic school children in Kenya provides an early warning signal of at least 1 of the 3 validated artemisinin resistance mutations circulating in all regions in Western Kenya sampled except Homa Bay and Kisii Counties. These signals in asymptomatic, mixed infections would have been missed without deep sequencing.
The Predictive Value of Myoglobin for Sepsis-Induced Cardiomyopathy
Authors: Chen Yue , Lin Xiaohong , Yu Guangwei 
Published: October 2024

Abstract

Myoglobin (MYO) levels can be detected in the early stages of sepsis and may serve as a potential biomarker for assessing the severity and prognosis of sepsis. Our study aims to explore the predictive value of MYO for sepsis-induced cardiomyopathy (SICM) in patients with sepsis. A single-center prospective cohort study was conducted, collecting demographic data, admission Sequential organ failure assessment (SOFA) scores, echocardiography results, MYO, N-terminal pro-B-type natriuretic peptide (NT-proBNP) results, and other related records from 158 patients with sepsis. Patients were divided into SICM and non-SICM groups based on the left ventricular ejection fraction (LEVF) results from echocardiography. Propensity score matching (PSM) was used to control for the confounding effects of age, gender, and BMI. Univariate and multivariate Logistic regression analyses were performed to identify factors associated with the occurrence of SICM; the receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of MYO for SICM. MYO levels were higher in the SICM group than in the non-SICM group (395.7 ng/ml vs 108.7 ng/ml, P < 0.05). Multivariate binary Logistic regression analysis showed that MYO is an independent risk factor for SICM in patients with sepsis (95% CI = 0.580–0.782, P < 0.05), with an area under the ROC curve (AUC) of 0.681 (95% CI: 0.580-0.782). MYO has good predictive value for SICM in patients with sepsis.
Effects of burr-hole surgery on MRI cerebral perfusion and stroke risk in adults with moyamoya angiopathy
Authors: Brandicourt Pierre , Calviere Lionel , Michelozzi Catarina , Rousseau Vanessa , Boetto Sergio , Darcourt Jean , Raposo Nicolas , Albucher Jean François , Viguier Alain , Cognard Christophe , Sol Jean Christophe , Olivot Jean Marc , Bonneville Fabrice 
Published: October 2024

Abstract

Purpose. Several surgical techniques have been proposed in moyamoya angiopathy (MMA) to reduce stroke risk; nevertheless, no one has clearly demonstrated its superiority. Burr-hole surgery allows the revascularization of large frontal areas and thus is increasingly used, but it has not been systematically evaluated in adults. We assessed the effect of burr-hole surgery as the only revascularization technique on MRI brain perfusion and stroke recurrence in adult patients with MMA. Methods. Retrospective study of consecutive adults patients with MMA and predominant frontal hypoperfusion treated by burr-hole surgery in a tertiary hospital. Parenchymal hypoperfusion rate on perfusion-weighted imaging (PWI) was compared using TMax before and 6 months after surgery. Perioperative complications and long-term risk of stroke/transient ischemic attack (TIA) were reviewed. Results. A total of 19 patients (11 women, mean age at surgery ± SD 42.4 ± 8.6 years) were included. A median of 7 (4–9) burr holes/hemisphere were performed on 34 hemispheres. Perioperative cerebral infarction occurred in 3 (15.9%) patients on 3 hemispheres (8.8%/hemisphere). The volume of slightly (Tmax ˃ 4 s) and severely (Tmax ˃ 6 s) hypoperfused parenchyma significantly decreased after surgery (p = 0.003 and p = 0.008, respectively). After a median follow-up of 72 (IQR 24.6) months, 4 strokes occurred in 3 patients (11.7%/hemisphere). The 2-year survival probability free of stroke/TIA was 85%. Conclusion. In adults with MMA and predominant frontal hypoperfusion, burr-hole surgery as the sole revascularization technique improved brain perfusion as measured with Tmax. Moreover the long-term risk of ischemic events and the rate of complications seemed similar to other techniques.
Taller forests are globally more drought-resistant
Authors: Chen Jing , Zhao Xingmin , Zhang Zhaoying , Ju Weimin , Gentine Pierre , Yang Yuting 
Published: October 2024

Abstract

Droughts exert a critical impact on forest growth, posing great challenges for forest sustainability globally. However, the mechanistic role of forest height (H) in modulating drought resistance remains poorly understood. Utilizing spaceborne observations of H and solar-induced chlorophyll fluorescence as a proxy for photosynthesis, here we show that taller forests consistently demonstrate higher resistance to drought stress globally, across varying levels of drought severity. This suggests that taller forests maintain higher stability under fluctuating climatic conditions. By synthesizing global forest root data, we found that this enhanced stability is closely tied to the deeper rooting systems of taller forests. Our findings underscore the critical role of H in forest ecosystem functioning and advocate for its inclusion as a key trait in ecosystem models to improve simulations of forest responses to climate change.
VGRCOT: a one-tube visual detection method for group B Streptococcus combining RPA and CRISPR/Cas12a for point-of-care testing in reproductive health
Authors: Ji Caixia , Ru Liqiang , Jiang Yayun 
Published: October 2024

Abstract

Group B Streptococcus (GBS) is a significant pathogen that causes perinatal infections, seriously threatening the health of pregnant women and newborns. Prophylactic antibiotic treatment for pregnant women who screen positive for GBS can notably reduce the incidence and fatality of neonatal infections. Herein, we developed a visual nucleic acid method for GBS that integrates RPA and CRISPR/Cas12a in a one-tube setup, termed VGRCOT. The VGRCOT method achieved one-tube detection by adding the appropriate reagents to the bottom and lid of the EP tube, respectively. By rigorous optimization of ssDNA-FQ reporter concentration, crRNA concentration, RPA reaction time, and CRISPR/Cas12a cleavage time, VGRCOT can exhibit fluorescence under ultraviolet light, enabling visual detection. Under optimal conditions, VGRCOT has a satisfactory selectivity and the detection limit was determined as 101 copies/reaction. Finally, VGRCOT also showed good performance comparable to qPCR in the actual detection of clinical specimens. Due to its ease of operation and convenient signal acquisition, VGRCOT shows promise for point-of-care testing in reproductive health.
The Mediating Effect of Metabolic Score for Insulin Resistance on the Link Between Cardiometabolic Index and Obstructive Sleep Apnea
Authors: Song Shangyi , Li Xuhao , Liu Yecun , Wang Xingxin , Zhang Wenhui , Yang Jiguo , Liu Yuanxiang 
Published: October 2024

Abstract

Background
Although there is considerable evidence that obstructive sleep apnea (OSA) is associated with cardiovascular and metabolic risks, such as insulin resistance and visceral fat accumulation, limited studies have explored how these risks are mediated by specific metabolic markers. The purpose of this study was to explore the relationship between Cardiometabolic Index (CMI) and OSA, and to pay special attention to the mediating role of insulin resistance metabolic score (METS-IR).
Methods
Data from 12,703 participants aged 20 and above were analyzed from the National Health and Nutrition Examination Survey (NHANES). CMI was the primary exposure variable, METS-IR served as the mediating variable, and OSA was the outcome. Multivariate logistic regression models were used to adjust for confounders and assess the relationship between CMI and OSA. Mediation analysis determined the proportion of CMI’s effect on OSA explained by METS-IR.
Results
Among 12,703 subjects, the prevalence of OSA was 30.88%. CMI was significantly associated with increased OSA risk, and participants with the highest quartile of CMI were significantly more likely to have OSA (OR = 2.06, 95% CI : 1.70–2.49). Mediation analysis showed that METS-IR accounted for 89.8% of the association between CMI and OSA, highlighting the key role of insulin resistance in this pathway.
Conclusions
CMI is a key predictor of OSA risk, which is mainly mediated by its effect on insulin resistance, as shown by METS-IR. These findings highlight the importance of addressing metabolic dysfunction in the prevention and management of OSA, and CMI and METS-IR provide valuable insights into clinical risk assessment in high-risk populations.
Cryoballoon vs. Robotic Magnetic Navigation-Guided Radiofrequency Ablation in Patients with Persistent Atrial Fibrillation: 5-year outcomes
Authors: Luo Qingzhi , Li Xiang , Xie Yun , Bao Yangyang , Wei Yue , Lin Changjian , Liu Zhuhui , Zhang Ning , Ling Tianyou , Chen Kang , Pan Wenqi , Wu Liqun , Jin Qi 
Published: October 2024

Abstract

Background
This study aimed to evaluate the long-term efficacy and clinical outcomes of catheter ablation performed with cryoballoon (CRYO) in comparison with robotic magnetic navigation (RMN) in patients with persistent atrial fibrillation (PersAF).
Methods and Results
A total of 200 patients with symptomatic PersAF were prospectively enrolled and assigned (1:1) to the CRYO or RMN guided-ablation group and then followed up over 5 years. The primary endpoint was freedom from atrial tachyarrhythmias (ATs) recurrence following a 3-month blanking period after the initial procedure. The secondary endpoints consisted of all-cause and cardiovascular rehospitalizations, rates of electrical cardioversions (ECs) and repeat ablations, new-onset neurological events, major bleeding events and the difference in CHA2DS2-VASc score at 5-year compared with baseline. After a median follow-up period of 60 months, 184 patients (93 in RMN, 91 in CRYO) completed the follow-up. Freedom from recurrent ATs was achieved in 44 out of 93 patients in the RMN group and 37 out of 91 patients in the CRYO group (47.3% vs. 40.7%, P = 0.32). There were no significant differences in the risk of all-cause and cardiovascular rehospitalizations, rates of ECs and repeat ablations, new-onset neurological events, and major bleeding at 5 years. OAC discontinuation was relatively common after ablation, 48.4% of patients with a CHA2DS2-VASc score ≥ 2 not on OAC therapy.
Conclusion
CRYO is comparable to RMN-guided ablation with respect to long-term freedom from ATs in patients with PersAF. Discontinuation of OAC after ablation is not rare even in patients at risk of stroke for continued OAC therapy.
Loupe-Assisted Thyroidectomy; Experience from Low Volume Centres
Authors: Venkataramani Nithya , Sachidananda Ravi , MK Manjunath , M Arshad Hussain , Rao Suraksha , Dore Suresh Babu , S Sunil Kumar G , Shankarnarayan Saikiran , N Karthik 
Published: October 2024

Abstract

Background
Thyroidectomy is an intricate surgery where nerve injury can cause significant morbidity. The use of magnification has revolutionised the modern-day otolaryngology practice. Its utility is now the standard of care for many ENT surgeries. Surgical loupes in Head and Neck surgery are emerging as a single important tool in reducing complications and improving precision. This retrospective study aimed to analyse the results of complications in thyroidectomy whilst using the loupes.
Methods
A retrospective study was conducted for 6 years. All the loupe-assisted thyroidectomies done by two surgeons were included in the study. All surgeries were performed with 2.5 X and some with 3.5 X magnification loupes. The incidence of voice change, hypocalcaemia, and secondary haemorrhage after thyroidectomy were noted.
Results
80 thyroidectomies were included, 39 were total thyroidectomies and the remaining were hemithyroidectomies. The age group was between 25 and 65 years. The mean stay in the hospital was approximately 2 days. Three patients had recurrent laryngeal nerve palsy, and 3 patients had transient hypocalcaemia which required calcium and magnesium supplementation. All the patients were operated with an intent to save the nerves and parathyroid glands.
Conclusions
The use of microsurgical techniques during thyroidectomy should be the standard of care as it reduces morbidity and minimises nerve injury.
Construction of a Novel Prognostic Risk Warning Model for Bunyavirus Patients Based on Inflammatory Indicators
Authors: Xiang Xu , Li Song , Dai Yue-qing 
Published: October 2024

Abstract

Objective To analyze the risk factors for poor prognosis in patients with SFTS and construct an early warning model. Methods 207 patients with SFTS admitted to Huazhong University of Science and Technology Affiliated Tongji Hospital from April 1, 2023 to July 18, 2024 were selected for retrospective analysis. According to the patients' prognosis, they were divided into survival group (n=133) and death group (n=74). The independent risk factors affecting the prognosis of patients were analyzed by univariate analysis and multivariate logistic regression analysis of general information and inflammatory indicators within 24 hours. An early warning model was established based on the independent risk factors. Results Age (OR = 1.162, 95% CI (1.102 ~ 1.236), P <0.001), viral load (OR = 2.669, 95% CI (1.764 ~ 4.239), P <0.001), PCT (OR = 2.758, 95%CI (1.586 ~ 5.231), P = 0.001), and IL-10 (OR = 1.005, 95% CI (1.001 ~ 1.009), P = 0.19) were independent risk factors affecting the prognosis of patients. A nomogram model was constructed based on the four risk factors, and the predictive performance of the model was good (ROC = 0.905, 95%CI (0.862 ~ 0.949), P <0.001). Conclusion The prognostic risk early warning model constructed in this study has good predictive effect, which can be used as a clinical tool for predicting the prognosis of SFTS patients.
Decoding the Immune Microenvironment of Secondary Chronic Myelomonocytic Leukemia due to DLBCL with CD19 CAR-T Failure by Single-cell RNA-seq
Authors: Li Xudong , Huang Hong , Shi Jianxiang , Liu Yuke , Gao Le , Ma Xiaojia , Gao Mengya , Sun Mingxia , Cao Haixia , Zhang Danfeng , Shen Na , Jiang Zhongxing , Cao Weijie , Bian Zhilei , Song Yongping , Wang Fang , Sun Hao , Xu Linping , Li wei 
Published: October 2024

Abstract

Multiple studies have confirmed the occurrence of second tumors as a rare incidence of CAR-T therapy, but one of the complications that does warrant in-depth exploration. According, given the relatively small number of reported second tumor types thus far, additional comprehensive occurrence and characterization of a new second tumor type after CAR-T therapy remains essential for understanding the risk of potential tumors with this therapy, as well as for defining the role of immune microenvironment in malignant transformation. In this article, a new second tumor type CMML was identified in a patient who had received CD19 CAR-T therapy for DLBCL. The immune microenvironment of both the pre- and post-treatment of secondary CMML and primary CMML were deeply profiled by ScRNA-seq. Our results demonstrated an enhanced inflammatory cytokines, chemokines, and immunosuppression state of monocytes/macrophages, which may inhibit the cytotoxicity of T/NKs in secondary CMML. In contrast, the cytotoxicity of T/NKs were enhanced in secondary CMML after treatment. Collectively, our results highlight a new type of second tumor, CMML after CAR-T therapy and provide a framework for defining the immune microenvironment of second tumor occurrence after CAR-T therapy. Our results also provide a rationale for targeting macrophages to strengthen CMML treatment.
Three-Dimensional Conductive Conjugated Polyelectrolyte Gels Facilitate Interfacial Electron Transfer for Improved Biophotovoltaic Performance
Authors: Bazan Guillermo , Chen Zhongxin , McCuskey Samantha , Zhang Weidong , Peng Benjamin , Quek Glenn , Jiang Yan , Ohayon David , Ong Shujian , Kundukad Binu , Mao Xianwen 
Published: October 2024

Abstract

Living biophotovoltaics represents a potentially green and sustainable method to generate bio-electricity through rewiring of photosynthetic electron transport chains (P-ETCs) to interconnect photosynthetic bacteria to electrodes. However, barriers to electron transfer across the abiotic/biotic interface hinders solar-to-electricity conversion efficiencies. Herein, we report on a facile method to improve interfacial electron transfer by combining the photosynthetic cyanobacterium Synechococcus elongatus PCC 7942 (Syne) with a conjugated polyelectrolyte (CPE) atop indium tin oxide (ITO) charge-collecting electrodes. By self-assembly of the CPE with Syne, soft and semitransparent Syne/CPE biocomposites are formed with three-dimensional conductive networks that exhibit mixed ionic-electronic conduction. These specific structures rewire an artificial P-ETC from bacteria to electrodes, allowing for improved and sustained photocurrent output compared to the performance of bacteria alone. Electrochemical studies confirmed the enhanced interfacial electron transport efficiency via the artificial P-ETC. Furthermore, microscopic photocurrent mapping for the biocomposites down to the single-cell level revealed a ~0.2 nanoampere output per cell, which translates to a 10-fold improvement relative to that of bare Syne, corroborating highly efficient long-range electron transport from Syne to the electrode via the three-dimensional CPE structure. This synergistic combination of biotic and abiotic materials underpins the significantly improved performance of biophotovoltaic devices, providing broader insights into the electron transfer mechanisms in a variety of bio-hybrid systems within semi-artificial photosynthesis and bioelectronic devices.