bluuebunny/crossref_metadata_2025_split huggingface dataset:
E2F1 Mediates SOX17 Deficiency–Induced Pulmonary Hypertension
Authors: Yi Dan , Liu Bin , Ding Hongxu , Li Shuai , Li Rebecca , Pan Jiakai , Ramirez Karina , Xia Xiaomei , Kala Mrinalini , Ye Qinmao , Lee Won Hee , Frye Richard E. , Wang Ting , Zhao Yutong , Knox Kenneth S. , Glembotski Christopher C. , Fallon Michael B. , Dai Zhiyu 
Published: September 2023

BACKGROUND:
Rare genetic variants and genetic variation at loci in an enhancer in SOX17 (SRY-box transcription factor 17) are identified in patients with idiopathic pulmonary arterial hypertension (PAH) and PAH with congenital heart disease. However, the exact role of genetic variants or mutations in SOX17 in PAH pathogenesis has not been reported.

METHODS:
SOX17 expression was evaluated in the lungs and pulmonary endothelial cells (ECs) of patients with idiopathic PAH. Mice with Tie2Cre-mediated Sox17 knockdown and EC-specific Sox17 deletion were generated to determine the role of SOX17 deficiency in the pathogenesis of PAH. Human pulmonary ECs were cultured to understand the role of SOX17 deficiency. Single-cell RNA sequencing, RNA-sequencing analysis, and luciferase assay were performed to understand the underlying molecular mechanisms of SOX17 deficiency–induced PAH. E2F1 (E2F transcription factor 1) inhibitor HLM006474 was used in EC-specific Sox17 mice.

RESULTS:
SOX17 expression was downregulated in the lung and pulmonary ECs from patients with idiopathic PAH. Mice with Tie2Cre-mediated Sox17 knockdown and EC-specific Sox17 deletion induced spontaneously mild pulmonary hypertension. Loss of endothelial Sox17 in EC exacerbated hypoxia-induced pulmonary hypertension in mice. Loss of SOX17 in lung ECs induced endothelial dysfunctions including upregulation of cell cycle programming, proliferative and antiapoptotic phenotypes, augmentation of paracrine effect on pulmonary arterial smooth muscle cells, impaired cellular junction, and BMP (bone morphogenetic protein) signaling. E2F1 signaling was shown to mediate the SOX17 deficiency–induced EC dysfunction. Pharmacological inhibition of E2F1 in Sox17 EC-deficient mice attenuated pulmonary hypertension development.

CONCLUSIONS:
Our study demonstrated that endothelial SOX17 deficiency induces pulmonary hypertension through E2F1. Thus, targeting E2F1 signaling represents a promising approach in patients with PAH.
Low rate of nonrelapse mortality in under-4-year-olds with ALL given chemotherapeutic conditioning for HSCT: a phase 3 FORUM study
Authors: Bader Peter , Pötschger Ulrike , Dalle Jean-Hugues , Moser Laura M. , Balduzzi Adriana , Ansari Marc , Buechner Jochen , Güngör Tayfun , Ifversen Marianne , Krivan Gergely , Pichler Herbert , Renard Marleen , Staciuk Raquel , Sedlacek Petr , Stein Jerry , Heusel Jan Robert , Truong Tony , Wachowiak Jacek , Yesilipek Akif , Locatelli Franco , Peters Christina 
Published: September 2023

Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is highly effective for treating pediatric high-risk or relapsed acute lymphoblastic leukemia (ALL). For young children, total body irradiation (TBI) is associated with severe late sequelae. In the FORUM study (NCT01949129), we assessed safety, event-free survival (EFS), and overall survival (OS) of 2 TBI-free conditioning regimens in children aged &lt;4 years with ALL. Patients received fludarabine (Flu), thiotepa (Thio), and either busulfan (Bu) or treosulfan (Treo) before HSCT. From 2013 to 2021, 191 children received transplantation and were observed for ≥6 months (median follow-up: 3 years). The 3-year OS was 0.63 (95% confidence interval [95% CI], 0.52-0.72) and 0.76 (95% CI, 0.64-0.84) for Flu/Thio/Bu and Flu/Thio/Treo (P = .075), respectively. Three-year EFS was 0.52 (95% CI, 0.41-0.61) and 0.51 (95% CI, 0.39-0.62), respectively (P = .794). Cumulative incidence of nonrelapse mortality (NRM) and relapse at 3 years were 0.06 (95% CI, 0.02-0.12) vs 0.03 (95% CI: &lt;0.01-0.09) (P = .406) and 0.42 (95% CI, 0.31-0.52) vs 0.45 (95% CI, 0.34-0.56) (P = .920), respectively. Grade &gt;1 acute graft-versus-host disease (GVHD) occurred in 29% of patients receiving Flu/Thio/Bu and 17% of those receiving Flu/Thio/Treo (P = .049), whereas grade 3/4 occurred in 10% and 9%, respectively (P = .813). The 3-year incidence of chronic GVHD was 0.07 (95% CI, 0.03-0.13) vs 0.05 (95% CI, 0.02-0.11), respectively (P = .518). In conclusion, both chemotherapeutic conditioning regimens were well tolerated and NRM was low. However, relapse was the major cause of treatment failure. This trial was registered at www.clinicaltrials.gov as #NCT01949129.
Interaction between N6-methyladenosine modification and the tumor microenvironment in colorectal cancer
Authors: Yao Jiali , Song Yeke , Yu Xiaoping , Lin Zhijie 
Published: September 2023

AbstractThe incidence and mortality of colorectal cancer (CRC) are rapidly increasing worldwide. Recently, there has been significant attention given to N6-methyladenosine (m6A), the most common mRNA modification, especially for its effects on CRC development. It is important to note that the progression of CRC would be greatly hindered without the tumor microenvironment (TME). The interaction between CRC cells and their surroundings can activate and influence complex signaling mechanisms of epigenetic changes to affect the survival of tumor cells with a malignant phenotype. Additionally, the TME is influenced by m6A regulatory factors, impacting the progression and prognosis of CRC. In this review, we describe the interactions and specific mechanisms between m6A modification and the metabolic, hypoxia, inflammatory, and immune microenvironments of CRC. Furthermore, we summarize the therapeutic role that m6A modification can play in the CRC microenvironment, and discuss the current status, limitations, and potential future directions in this field. This review aims to provide new insights into the molecular targets and theoretical foundations for the treatment of CRC.
The benefits of rehabilitation exercise in improving chronic traumatic encephalopathy: recent advances and future perspectives
Authors: Huang Yin-qiong , Wu Zhe , Lin Shu , Chen Xiang-rong 
Published: September 2023

AbstractTraumatic encephalopathy syndrome (TES) is used to describe the clinical manifestations of chronic traumatic encephalopathy (CTE). However, effective treatment and prevention strategies are lacking. Increasing evidence has shown that rehabilitation training could prevent cognitive decline, enhance brain plasticity, and effectively improve neurological function in neurodegenerative diseases. Therefore, the mechanisms involved in the effects of rehabilitation exercise therapy on the prognosis of CTE are worth exploring. The aim of this article is to review the pathogenesis of CTE and provide a potential clinical intervention strategy for CTE.
Comprehensive analysis on the regulation of differentially expressed of mRNA and ncRNA in different ovarian stages of ark shell Scapharca broughtonii
Authors: Wang Wenjing , Wu Biao , Liu Zhihong , Sun Xiujun , Zhou Liqing , Xu Wandong , Yu Tao , Zheng Yanxin , Zhang Shihao 
Published: September 2023

Abstract
Background
Ovarian development is an important prerequisite and basis for animal reproduction. In many vertebrates, it is regulated by multiple genes and influenced by sex steroid hormones and environmental factors. However, relative information is limited in shellfish. To explore the biological functions and molecular mechanisms of mRNA and non-coding RNA that regulate ovarian development in Scapharca broughtonii, we performed whole transcriptome sequencing analysis on ovaries at three developmental stages. Furthermore, the biological processes involved in the differential expression of mRNA and ncRNA were analyzed.

Results
A total of 11,342 mRNAs, 6897 lncRNAs, 135 circRNAs, and 275 miRNAs were differentially expressed. By mapping the differentially expressed RNAs from the three developmental stages of Venn diagram, multiple groups of shared mRNAs and lncRNAs were found to be associated with ovarian development, with some mRNA and ncRNA functions associated with steroid hormone. In addition, we constructed and visualized the lncRNA/circRNA-miRNA-mRNA network based on ceRNA targeting relationships.

Conclusions
These findings may facilitate our further understanding the mRNA and ncRNAs roles in the regulation of shellfish reproduction.
Prediction of episode of hemodynamic instability using an electrocardiogram based analytic: a retrospective cohort study
Authors: Benson Bryce , Belle Ashwin , Lee Sooin , Bassin Benjamin S. , Medlin Richard P. , Sjoding Michael W. , Ward Kevin R. 
Published: September 2023

Abstract
Background
Predicting the onset of hemodynamic instability before it occurs remains a sought-after goal in acute and critical care medicine. Technologies that allow for this may assist clinicians in preventing episodes of hemodynamic instability (EHI). We tested a novel noninvasive technology, the Analytic for Hemodynamic Instability-Predictive Indicator (AHI-PI), which analyzes a single lead of electrocardiogram (ECG) and extracts heart rate variability and morphologic waveform features to predict an EHI prior to its occurrence.

Methods
Retrospective cohort study at a quaternary care academic health system using data from hospitalized adult patients between August 2019 and April 2020 undergoing continuous ECG monitoring with intermittent noninvasive blood pressure (NIBP) or with continuous intraarterial pressure (IAP) monitoring.

Results
AHI-PI’s low and high-risk indications were compared with the presence of EHI in the future as indicated by vital signs (heart rate > 100 beats/min with a systolic blood pressure < 90 mmHg or a mean arterial blood pressure of < 70 mmHg). 4,633 patients were analyzed (3,961 undergoing NIBP monitoring, 672 with continuous IAP monitoring). 692 patients had an EHI (380 undergoing NIBP, 312 undergoing IAP). For IAP patients, the sensitivity and specificity of AHI-PI to predict EHI was 89.7% and 78.3% with a positive and negative predictive value of 33.7% and 98.4% respectively. For NIBP patients, AHI-PI had a sensitivity and specificity of 86.3% and 80.5% with a positive and negative predictive value of 11.7% and 99.5% respectively. Both groups performed with an AUC of 0.87. AHI-PI predicted EHI in both groups with a median lead time of 1.1 h (average lead time of 3.7 h for IAP group, 2.9 h for NIBP group).

Conclusions
AHI-PI predicted EHIs with high sensitivity and specificity and within clinically significant time windows that may allow for intervention. Performance was similar in patients undergoing NIBP and IAP monitoring.
Facilitators and barriers for tuberculosis preventive treatment among patients with latent tuberculosis infection: a qualitative study
Authors: Manoharan Anusha , Siti Nur Farhana H. , Manimaran K. , Khoo Ee Ming , Koh Wen Ming 
Published: September 2023

Abstract
Background
Various factors influence tuberculosis preventive treatment (TPT) decisions thus it is important to understand the health beliefs and concerns of patients before starting TPT to ensure treatment compliance. This study aims to explore facilitators and barriers for TPT among patients diagnosed with Latent Tuberculosis infection (LTBI) attending six primary healthcare clinics in Selangor, Malaysia.

Method
In-depth interviews were conducted face-to-face or via telephone among patients with a clinical diagnosis of LTBI using a semi-structured topic guide developed based on the common-sense model of self-regulation and literature review. Audio recordings of interviews were transcribed verbatim and analysed thematically.

Results
We conducted 26 In-depth interviews; Good knowledge of active tuberculosis (TB) and its associated complications, including the perceived seriousness and transmissibility of active TB, facilitates treatment. LTBI is viewed as a concern when immune status is compromised, thus fostering TPT. However, optimal health is a barrier for TPT. Owing to the lack of knowledge, patients rely on healthcare practitioners (HCPs) to determine their treatment paths. HCPs possessing comprehensive knowledge play a role in facilitating TPT whereas barriers to TPT encompass misinterpretation of tuberculin skin test (TST), inadequate explanation of TST, and apprehensions about potential medication side effects.

Conclusions
Knowledge of LTBI can influence TPT uptake and patients often entrust their HCPs for treatment decisions. Improving knowledge of LTBI both among patients and HCPs can lead to more effective doctor-patient consultation and consequently boost the acceptance of TPT. Quality assurance should be enhanced to ensure the effective usage of TST as a screening tool.
Clinical presentations and treatment outcomes of Hashimoto encephalopathy at Siriraj Hospital – Thailand’s largest national tertiary referral center
Authors: Dumrikarnlert Chaisak , Thakolwiboon Smathorn , Senanarong Vorapun 
Published: September 2023

Abstract
Background
Hashimoto encephalopathy has multiple clinical presentations, and other than the presence of thyroid antibody, laboratory and imaging investigations are all non-specific. Data specific to the clinical presentations and treatment outcomes of patients with Hashimoto encephalopathy in Thailand remain scarce.

Objectives
To retrospectively investigate the clinical presentations and treatment outcomes of patients with Hashimoto encephalopathy at Siriraj Hospital.

Methods
Patients who presented with acute encephalopathy at our center during July 2012-March 2017 were evaluated for eligibility. The inclusion criteria were positive anti-thyroperoxidase (anti-TPO) or anti-thyroglobulin (anti-Tg) in serum with negative neuronal antibody in serum or cerebral spinal fluid (CSF). Clinical presentations, symptom duration, laboratory results of thyroid status and thyroid autoantibody, CSF study, and clinical outcomes were collected.

Results
Of the 204 patients who presented with encephalopathy, 31 (15.2%) were positive for the anti-TPO or anti-Tg antibody. Of those, 13 patients met the diagnostic criteria for Hashimoto encephalopathy. Clinical presentations included cognitive impairment (76.9%), clouding of consciousness (46.2%), and behavior change (30.8%). The neuropsychiatric presentations were visual hallucination (30.8%), auditory hallucination (15.4%), delusion (7.7%), and mood disturbance (23.1%). Other clinical presentations included seizure (38.5%), abnormal movement (23.1%), sleep disturbance (38.5%), ataxia (46.2%), stroke-like episode (15.4%), and fever (15.4%). Most patients (76.9%) had onset within < 3 months. Regarding outcomes, 1 patient who did not receive corticosteroid died from status epilepticus and septic shock. Among the 12 patients who received corticosteroid, 9 (75%) had marked improvement, 1 (8.3%) had slight improvement, and 2 (16.6%) had no clinical improvement. Seven patients (53.9%) had normal thyroid function, 4 patients (30.8%) had subclinical hypothyroidism, and 2 patients (15.4%) had subclinical hyperthyroidism.

Conclusions
The results of this study revealed cognitive impairment, neuropsychiatric symptoms, seizure, ataxia, and sleep disturbance to be common manifestations of Hashimoto encephalopathy. This condition should always be considered in individuals with subacute onset of unexplained cognitive impairment or cerebellar ataxia. Laboratory and neuroimaging investigations were all found to be nonspecific in Hashimoto encephalopathy. Most patients responded well to treatment, so clinical suspicion and early diagnosis and treatment will lead to improved patient outcomes.
Investigating the impact of diameters and thread designs on the Biomechanics of short implants placed in D4 bone: a 3D finite element analysis
Authors: Alqahtani Ali Robaian , Desai Shrikar R. , Patel Jignesh R. , Alqhtani Nasser Raqe , Alqahtani Abdullah Saad , Heboyan Artak , Fernandes Gustavo V. O. , Mustafa Mohammed , Karobari Mohamed Isaqali 
Published: September 2023

Abstract
Background
Dental implants emerge as a dependable and efficacious alternative for patients experiencing partial or complete tooth loss. The stability of these implants is influenced by surface topography and macro-level design. In cases where the height of the maxillary posterior region is diminished, employing short implants can prove advantageous. With the aim of examining the distribution of von Mises stress, strain, and micromovement in D4 bone quality surrounding platform-switched short implants, measuring 6 mm in length and featuring diameters ranging from 4 to 6 mm, as well as different thread designs, an in-depth finite element analysis was conducted under immediate loading conditions.

Methodology
A 3D finite element model was constructed to simulate maxillary molar crowns, incorporating an implant with a length of 6 mm and varying diameters and thread designs. The diameters utilized were 4/3.6 mm, 5/4 mm, and 6/4.8 mm, while the thread designs included buttress, square, and triangle patterns. Each model underwent analysis with a 100 N force applied in two directions: vertical and oblique, relative to the long axis of the implant. Stress, strain, and micromovement in the peri-implant region were recorded, employing the Ansys Workbench R v.18.1 software for modelling and analysis.

Results
When comparing all three diameters, the wide diameter (6 mm threads) exhibited the lowest values of peri-implant von Mises stresses (3.3 MPa and 35.1 MPa), strains (194 Ɛ and 484 Ɛ), and micromovements (0.7 μm and 1.3 Ɛ) subjected to axial and non-axial loading of a 100 N force. Notably, square microthreads yielded the most favorable stress parameters among the different thread shapes, manifesting the minimum values of stress, strains, and micromovements in their vicinity.

Conclusion
For the treatment of atrophic ridges or in scenarios necessitating extensive surgical preparation of the implant site, a combination of short implants, wide diameters, and platform switching can be employed. In situations with reduced bone height and the requirement for an implant-supported prosthesis to replace a missing permanent maxillary molar, the utilization of wide-diameter platform-switched short implants measuring 6 mm in length, featuring a square thread design, should be taken into consideration.
Application of PBL combined with traditional teaching in the Immunochemistry course
Authors: Song Pingping , Shen Xiangchun 
Published: September 2023

AbstractBackgroundThe problem-based learning (PBL) model has been widely carried out in many fields of medical colleges and universities. Immunochemistry as a cross-disciplinary science plays a vital role in preventing the occurrence of diseases and bridging the development of Life Science and Medicine. But now the Immunochemistry course still lacks the teaching practice in PBL. To explore the significance of PBL applied in the Immunochemistry course, the effect of the PBL model on the learning of undergraduates majoring in Chemicobiology was systematically evaluated.MethodsThe teaching objects were the undergraduates majoring in Chemicobiology from Guizhou Medical University. The PBL model was applied in the Immunochemistry course. 62 undergraduates in Grade 2018 were set as the control group and adopted the traditional expository model. 93 undergraduates in Grades 2019–2020 were separately set as the experimental groups, which adopted the PBL model based on traditional lecture-based learning. In the PBL model, six cases related to course contents were designed for the students to complete. The final exams of the undergraduates in Grades 2018–2020 were analyzed by the score ranges (< 60 points, 60–69 points, 70–79 points, and ≥ 80 points) and nonparametric test. Finally, the questionnaire survey about the teaching evaluation was performed in Grades 2019–2020.ResultsIn Grades 2019 and 2020, the excellent rates (≥ 80 points), pass rates (≥ 60 points), fail rates (< 60 points), and average scores of the undergraduates were separately about 29%, 91.11% and 93.75%, 6.25%, and 8.89%, and 72.55 and 74.45 points. But in Grade 2018, the excellent rate, pass rate, failure rate, and average score of the undergraduates were separately 9.68%, 59.68%, 40.32%, and 62.55 points. By the statistical analysis, it was found that the excellent rates (χ2 = 8.317,P < 0.005) and pass rates (χ2 = 24.52,P < 0.0001) in Grades 2018–2020 were different, of which Grade 2020were the highest (29.17%, 93.75%) and Grade 2018 was the lowest (9.68%, 59.68%). The average score, excellent rate, and pass rate in Grade 2018 had significant differences with Grade 2019 (P < 0.0001,P < 0.0167) and Grade 2020 (P < 0.001,P < 0.0167). The questionnaire survey also showed that the student’s learning interests, independent problem-solving ability, knowledge structure system, and scientific thought and teamwork awareness were enhanced. In Grades 2019 and 2020, the ICC (95% CI) of criterion validity and inter-rater reliability were separately 0.42/0.34 and 0.81/0.80 (P < 0.0001).ConclusionThe combination of PBL and traditional expository models played positive roles in the student’s learning in the Immunochemistry course.
Induced pluripotent stem cells: ex vivo models for human diseases due to mitochondrial DNA mutations
Authors: Chen Chao , Guan Min-Xin 
Published: September 2023

AbstractMitochondria are essential organelles for cellular metabolism and physiology in eukaryotic cells. Human mitochondria have their own genome (mtDNA), which is maternally inherited with 37 genes, encoding 13 polypeptides for oxidative phosphorylation, and 22 tRNAs and 2 rRNAs for translation. mtDNA mutations are associated with a wide spectrum of degenerative and neuromuscular diseases. However, the pathophysiology of mitochondrial diseases, especially for threshold effect and tissue specificity, is not well understood and there is no effective treatment for these disorders. Especially, the lack of appropriate cell and animal disease models has been significant obstacles for deep elucidating the pathophysiology of maternally transmitted diseases and developing the effective therapy approach. The use of human induced pluripotent stem cells (iPSCs) derived from patients to obtain terminally differentiated specific lineages such as inner ear hair cells is a revolutionary approach to deeply understand pathogenic mechanisms and develop the therapeutic interventions of mitochondrial disorders. Here, we review the recent advances in patients-derived iPSCs as ex vivo models for mitochondrial diseases. Those patients-derived iPSCs have been differentiated into specific targeting cells such as retinal ganglion cells and eventually organoid for the disease modeling. These disease models have advanced our understanding of the pathophysiology of maternally inherited diseases and stepped toward therapeutic interventions for these diseases.
A novel near-infrared EGFR targeting probe for metastatic lymph node imaging in preclinical mouse models
Authors: Xie Diya , Li Yunlong , Shi Jiahong , Zhu Yao Ping , Wang Yiqing , Butch Christopher J. , Wang Zhiyong 
Published: September 2023

AbstractFor the treatment of patients with oral squamous cell carcinoma (OSCC), the imaging of cervical lymph nodes and the evaluation of metastastic progression are of great significance. In recent years, the development of new non-radioactive lymph node tracers has been an area of intense research. Here, we report the synthesis, good biocompatibility, and in vivo evaluation of a new small molecule near-infrared (NIR) fluorescence probe by the conjugation of Lapatinib to S0456 (LP-S). We show that like Lapatinib, LP-S binds to the epidermal growth factor receptor (EGFR) resulting in high quality fluorescence imaging of metastatic lymph nodes in OSCC mouse models. After local injection of LP-S into the tumor, the lymphatic drainage pathway and lymph nodes can be clearly identified by NIR fluorescence imaging. Further, the LP-S probe shows higher contrast and longer retention in metastatic lymph nodes, allowing them to be differentiated from normal lymph nodes, and affording a new choice for fluorescence-guided surgery.
Graphical abstract