bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research on the wound healing effect of Shengji Huayu Formula ethanol extract-derived fractions in streptozotocin-induced diabetic ulcer rats
Authors: Zhang Jing-Ting , Wu Min-Feng , Ma Ming-Hua , Zhao Liang , Zhu Jian-Yong , Nian Hua , Li Fu-Lun 
Published: March 2023

Abstract
Background
Diabetic ulcer is a common complication of diabetes. It is characterized by a long-term disease course and high recurrence rate. Shengji Huayu Formula (SHF) is an effective formula for treating diabetic ulcers. However, the specific effective parts of SHF remain unclear. Clarifying the active polar site of SHF would be helpful to refine research on the components in SHF that promote wound healing. This research aims to focus on evaluating the activity of polar fractions.

Methods
A diabetic rat model was established by intraperitoneally injecting streptozotocin (STZ) and was adopted to confirm the therapeutic effect of SHF. Four different polarity parts were extracted from SHF and prepared into a cream to evaluate the activity. High-performance liquid chromatography (HPLC) was used to detect chemical constituents in chloroform extracts.

Results
It was discovered that dracorhodin, aloe-emodin, rhein, imperatorin, emodin, isoimperatorin, chrysophanol, physcion, and tanshinone IIA were the main components of the chloroform extract from SHF. The results revealed that chloroform extract could effectively accelerate diabetic wound healing by promoting collagen regeneration and epidermal repair. Chloroform extract of SHF could stimulate the generation of vascular endothelial growth factor (VEGF). The results are also indicated that the effective active fraction was the chloroform part, and the method of detecting the main chemical constituents in the active part was successfully established.

Conclusion
SHF could improve diabetic ulcers by promoting granulation tissue synthesis. In this study, four polar parts (petroleum ether, chloroform, ethylacetate, n-butanol) were extracted from a 95% ethanol extract. In contrast, chloroform polar parts showed a higher wound closure rate, stimulated more collagen regeneration and promoted more production of vascular endothelial cells. In conclusion, the chloroform extract of SHF was the effective polar part in ameliorating diabetic wound healing.
Validation of IFMSA social accountability assessment tool: exploratory and confirmatory factor analysis
Authors: Coşkun Özlem , Timurçin Utku , Kıyak Yavuz Selim , Budakoğlu Işıl İrem 
Published: March 2023

Abstract
Background
IFMSA Social Accountability Assessment Tool has been developed for medical students by medical students to assess medical schools. However, its psychometric characteristics are unknown since it was developed without any analysis. We aimed to reveal its reliability and validity.

Methods
1122 undergraduate medical students from various years in Gazi University Faculty of Medicine have participated in the study. They have answered the Turkish version of IFMSA Social Accountability Assessment Tool created through a translation process by experts. Exploratory and confirmatory factor analyses were carried out.

Results
Exploratory factor analysis showed that factor loadings were between 0.46 and 0.73 for Factor 1, 0.68 and 0.87 for Factor 2. The two-factor model, which consists of “Community Centeredness” and “Socio-Demographic Characteristics”, was evaluated through confirmatory factor analysis. The goodness-of-fit statistics of the model showed well-fit: CMIN/df 4.46, GFI 0.96, CFI 0.95, RMSEA 0.05, SRMR 0.03. Standardized regression weights were between 0.43 and 0.77.

Conclusion
The tool has acceptable psychometric characteristics, with good reliability and validity. It could be considered as a point of departure for the change in the way of being socially accountable since it enables medical students to explore the weak areas of their medical schools in terms of social accountability.
Towards more efficient and robust evaluation of sepsis treatment with deep reinforcement learning
Authors: Yu Chao , Huang Qikai 
Published: March 2023

Abstract
Background
In recent years, several studies have applied advanced AI methods, i.e., deep reinforcement learning, in discovering more efficient treatment policies for sepsis. However, due to a paucity of understanding of sepsis itself, the existing approaches still face a severe evaluation challenge, that is, how to properly evaluate the goodness of treatments during the learning process and the effectiveness of the final learned treatment policies.

Methods
We propose a deep inverse reinforcement learning with mini-tree model that integrates different aspects of factors into the reward formulation, including the critical factors in causing mortality and the key indicators in the existing sepsis treatment guidelines, in order to provide a more comprehensive evaluation of treatments during learning. A new off-policy evaluation method is then proposed to enable more robust evaluation of the learned policies by considering the weighted averaged value functions estimated until the current step.

Results
Results in the MIMIC-III dataset show that the proposed methods can achieve more efficient treatment policies with higher reliability compared to those used by the clinicians.

Conclusions
A more sound and comprehensive evaluation of treatments of sepsis should consider the most critical factors in infulencing the mortality during treatment as well as those key indicators in the existing sepsis diagnosis guidelines.
Enzyme-catalyzed synthesis of selenium-doped manganese phosphate for synergistic therapy of drug-resistant colorectal cancer
Authors: Pei Manman , Liu Kaiyuan , Qu Xiao , Wang Kairuo , Chen Qian , Zhang Yuanyuan , Wang Xinyue , Wang Zheng , Li Xinyao , Chen Feng , Qin Huanlong , Zhang Yang 
Published: March 2023

Abstract
Background
The development of multidrug resistance (MDR) during postoperative chemotherapy for colorectal cancer substantially reduces therapeutic efficacy. Nanostructured drug delivery systems (NDDSs) with modifiable chemical properties are considered promising candidates as therapies for reversing MDR in colorectal cancer cells. Selenium-doped manganese phosphate (Se-MnP) nanoparticles (NPs) that can reverse drug resistance through sustained release of selenium have the potential to improve the chemotherapy effect of colorectal cancer.

Results
Se-MnP NPs had an organic–inorganic hybrid composition and were assembled from smaller-scale nanoclusters. Se-MnP NPs induced excessive ROS production via Se-mediated activation of the STAT3/JNK pathway and a Fenton-like reaction due to the presence of manganese ions (Mn2+). Moreover, in vitro and in vivo studies demonstrated Se-MnP NPs were effective drug carriers of oxaliplatin (OX) and reversed multidrug resistance and induced caspase-mediated apoptosis in colorectal cancer cells. OX@Se-MnP NPs reversed MDR in colorectal cancer by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (e.g., ABCB1, ABCC1 and ABCG2). Finally, in vivo studies demonstrated that OX-loaded Se-MnP NPs significantly inhibited proliferation of OX-resistant HCT116 (HCT116/DR) tumor cells in nude mice.

Conclusions
OX@Se-MnP NPs with simple preparation and biomimetic chemical properties represent promising candidates for the treatment of colorectal cancer with MDR.
The effect of endoscopic transsphenoidal somatotroph tumors resection on pituitary hormones: systematic review and meta-analysis
Authors: Nie Ding , Fang Qiuyue , Wong Wakam , Gui Songbai , Zhao Peng , Li Chuzhong , Zhang Yazhuo 
Published: March 2023

AbstractPurposeCurrently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative effects on pituitary endocrine function, and the pituitary function of somatotroph tumors is a point of particular concern after the operation. This study aimed to conduct a meta-analysis on the effect of endoscopic transsphenoidal somatotroph tumor resection on pituitary function.MethodsA systematic literature search was conducted for articles that included the evaluation of pituitary target gland before and after endoscopic transsphenoidal pituitary tumor resection and were published between 1992 and 2022 in PubMed, Cochrane, and Ovid MEDLINE.ResultsSixty-eight studies that included biochemical remission rates in 4524 somatotroph tumors were concluded. According to the 2000 consensus, the biochemical remission rate after transsphenoidal endoscopic surgery was 66.4% (95%CI, 0.622–0.703;P = 0.000), the biochemical remission rate was 56.2% according to the 2010 consensus (95%CI, 0.503–0.620;P = 0.041), and with the rate of biochemical remission ranging from 30.0 to 91.7% with investigator’s definition. After endoscopic resection, adrenal axis dysfunction was slightly higher than that before surgery, but the difference was not statistically significant. Hypothyroidism was 0.712 times higher risk than that before surgery (OR = 0.712; 95%CI, 0.527–0.961;P = 0.027). Hypogonadism was 0.541 times higher risk than that before surgery (OR = 0.541; 95%CI, 0.393–0.746;P = 0.000). Hyperprolactinemia was 0.131 times higher risk than that before surgery (OR = 0.131; 95%CI, 0.022–0.783;P = 0.026). The incidence of pituitary insufficiency was 1.344 times the risk before surgery after endoscopic resection of somatotroph tumors, but the difference was not statistically significant.ConclusionsIn patients with somatotroph tumors after undergoing endoscopic surgery, the risk of dysfunction and pituitary insufficiency tend to increase, while preoperative thyroid insufficiency, gonadal insufficiency, and hyperprolactinemia will be partially relieved.
Association between colorectal cancer and expression levels of miR-21, miR-17-5P, miR-155 genes and the presence of Fusobacterium nucleatum in biopsy samples obtained from Iranian patients
Authors: Bostanshirin Nazila , Hajikhani Bahareh , Vaezi Amir Abbas , Kermanian Fatemeh , Sameni Fatemeh , Yaslianifard Somayeh , Goudarzi Mehdi , Dadashi Masoud 
Published: March 2023

Abstract
Background
Colorectal cancer (CRC) is considered the second-deadliest and third-most common malignancy worldwide. Studying the carcinogenic mechanism of bacteria or their role in aggravating cancer can be precious. Fusobacterium nucleatum (F. nucleatum) is one of the important bacteria in the occurrence and spread of CRC. In this study, we investigated the expression levels of miR-21, miR-17-5P, miR-155, and the relative frequency of F. nucleatum in biopsy samples from patients with CRC.

Method
DNA and RNA samples were extracted using a tissue extraction kit, and then cDNAs were synthesized using a related kit. Based on the sequence of miR-17-5P, miR-21, and miR-155 genes, F. nucleatum specific 16srRNA and bacterial universal16srRNA specific primers were selected, and the expression levels of the target genes were analyzed using the Real-Time PCR method.

Results
The expression level of miR-21, miR-17-5P, and miR-155 genes showed a significant increase in the cancer group. Also, the expression of the mentioned miRNAs was significantly raised in the positive samples for F. nucleatum presence. The relative frequency of F. nucleatum in the cancer group was significantly increased compared to the control group.

Conclusion
Due to the changes in the expression of genes involved in causing CRC in the presence of F. nucleatum, it is possible to prompt identification and provide therapeutic solutions to cancer patients by studying their microbial profiles and the expression changes of different selected genes.
Surgical treatment versus observation in moderate intermittent exotropia (SOMIX): study protocol for a randomized controlled trial
Authors: Shen Tao , Chen Jingchang , Kang Ying , Deng Daming , Lin Xiaoming , Wu Heping , Li Jinrong , Wang Zhonghao , Qiu Xuan , Jin Ling , Yan Jianhua 
Published: March 2023

AbstractBackgroundIntermittent exotropia (IXT) is the most common type of strabismus in China, but the best treatment and optimal timing of intervention for IXT remain controversial, particularly for children with moderate IXT who manifest obvious exodeviation frequently but with only partial impairment of binocular single vision. The lack of randomized controlled trial (RCT) evidence means that the true effectiveness of the surgical treatment in curing moderate IXT is still unknown. The SOMIX (surgical treatment versus observation in moderate intermittent exotropia) study has been designed to determine the long-term effectiveness of surgery for the treatment and the natural history of IXT among patients aged 5 to 18 years old.Methods/designA total of 280 patients between 5 and 18 years of age with moderate IXT will be enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. After initial clinical assessment, all participants will be randomized to receive surgical treatment or observation, and then be followed up for 5 years. The primary objective is to compare the cure rate of IXT between the surgical treatment and observation group. The secondary objectives are to identify the predictive factors affecting long-term outcomes in each group and to observe the natural course of IXT.DiscussionThe SOMIX trial will provide important guidance regarding the moderate IXT and its managements and modify the treatment strategies of IXT.Trial registrationClinicalTrials.gov:NCT 02736526. Registered April 13, 2016
Molecular characterisation of 36 multilocus imprinting disturbance (MLID) patients: a comprehensive approach
Authors: Bilo Larissa , Ochoa Eguzkine , Lee Sunwoo , Dey Daniela , Kurth Ingo , Kraft Florian , Rodger Fay , Docquier France , Toribio Ana , Bottolo Leonardo , Binder Gerhard , Fekete György , Elbracht Miriam , Maher Eamonn R. , Begemann Matthias , Eggermann Thomas 
Published: March 2023

Abstract
Background
Imprinting disorders (ImpDis) comprise diseases which are caused by aberrant regulation of monoallelically and parent-of-origin-dependent expressed genes. A characteristic molecular change in ImpDis patients is aberrant methylation signatures at disease-specific loci, without an obvious DNA change at the specific differentially methylated region (DMR). However, there is a growing number of reports on multilocus imprinting disturbances (MLIDs), i.e. aberrant methylation at different DMRs in the same patient. These MLIDs account for a significant number of patients with specific ImpDis, and several reports indicate a central role of pathogenic maternal effect variants in their aetiology by affecting the maturation of the oocyte and the early embryo. Though several studies on the prevalence and the molecular causes of MLID have been conducted, homogeneous datasets comprising both genomic and methylation data are still lacking.

Results
Based on a cohort of 36 MLID patients, we here present both methylation data obtained from next-generation sequencing (NGS, ImprintSeq) approaches and whole-exome sequencing (WES). The compilation of methylation data did not reveal a disease-specific MLID episignature, and a predisposition for the phenotypic modification was not obvious as well. In fact, this lack of epigenotype–phenotype correlation might be related to the mosaic distribution of imprinting defects and their functional relevance in specific tissues.

Conclusions
Due to the higher sensitivity of NGS-based approaches, we suggest that ImprintSeq might be offered at reference centres in case of ImpDis patients with unusual phenotypes but MLID negative by conventional tests. By WES, additional MLID causes than the already known maternal effect variants could not be identified, neither in the patients nor in the maternal exomes. In cases with negative WES results, it is currently unclear to what extent either environmental factors or undetected genetic variants contribute to MLID.
Modeling nervous system tumors with human stem cells and organoids
Authors: Duan Jie , Wang Yuan 
Published: March 2023

AbstractNervous system cancers are the 10th leading cause of death worldwide, many of which are difficult to diagnose and exhibit varying degrees of treatment resistance. The limitations of existing cancer models, such as patient-derived xenograft (PDX) models and genetically engineered mouse (GEM) models, call for the development of novel preclinical cancer models to more faithfully mimic the patient’s cancer and offer additional insights. Recent advances in human stem cell biology, organoid, and genome-editing techniques allow us to model nervous system tumors in three types of next-generation tumor models: cell-of-origin models, tumor organoids, and 3D multicellular coculture models. In this review, we introduced and compared different human stem cell/organoid-derived models, and comprehensively summarized and discussed the recently developed models for various primary tumors in the central and peripheral nervous systems, including glioblastoma (GBM), H3K27M-mutant Diffuse Midline Glioma (DMG) and H3G34R-mutant High-grade Glioma (HGG), Low-grade Glioma (LGG), Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), Medulloblastoma (MB), Atypical Teratoid/rhabdoid Tumor (AT/RT), and meningioma. We further compared these models with PDX and GEM models, and discussed the opportunities and challenges of precision nervous cancer modeling with human stem cells and organoids.
A single mild juvenile TBI in male mice leads to regional brain tissue abnormalities at 12 months of age that correlate with cognitive impairment at the middle age
Authors: Obenaus Andre , Rodriguez-Grande Beatriz , Lee Jeong Bin , Dubois Christophe J. , Fournier Marie-Line , Cador Martine , Caille Stéphanie , Badaut Jerome 
Published: March 2023

AbstractTraumatic brain injury (TBI) has the highest incidence amongst the pediatric population and its mild severity represents the most frequent cases. Moderate and severe injuries as well as repetitive mild TBI result in lasting morbidity. However, whether a single mild TBI sustained during childhood can produce long-lasting modifications within the brain is still debated. We aimed to assess the consequences of a single juvenile mild TBI (jmTBI) at 12 months post-injury in a mouse model. Non-invasive diffusion tensor imaging (DTI) revealed significant microstructural alterations in the hippocampus and the in the substantia innominata/nucleus basalis (SI/NB), structures known to be involved in spatial learning and memory. DTI changes paralled neuronal loss, increased astrocytic AQP4 and microglial activation in the hippocampus. In contrast, decreased astrocytic AQP4 expression and microglia activation were observed in SI/NB. Spatial learning and memory were impaired and correlated with alterations in DTI-derived derived fractional ansiotropy (FA) and axial diffusivity (AD). This study found that a single juvenile mild TBI leads to significant region-specific DTI microstructural alterations, distant from the site of impact, that correlated with cognitive discriminative novel object testing and spatial memory impairments at 12 months after a single concussive injury. Our findings suggest that exposure to jmTBI leads to a chronic abnormality, which confirms the need for continued monitoring of symptoms and the development of long-term treatment strategies to intervene in children with concussions.
Interactions at the point of firearm purchase and subsequent use of locking devices
Authors: Bandel Shelby L. , Bond Allison E. , Anestis Michael D. 
Published: March 2023

Abstract
Background
Firearms account for over 40,000 deaths in the USA each year in addition to thousands of nonfatal injuries. One notable prevention strategy for firearm-related fatalities and nonfatal injuries is safe storage. Safe storage of firearms emphasizes using storage mechanisms that limit ready access of firearms to unauthorized users. Cable locks are one safe storage option that is easy to access and typically free, as they are included in many firearms sales. The present study examined the extent to which firearms retailers notifying purchasers at the point of sale about the included cable locks was associated with subsequent locking device use in two large samples and three subsamples. Exploratory analyses then examined demographic factors associated with frequency of seller notification of locks.

Methods
Sample 1 included 1203 firearm owners and sample 2 included 1556 firearm owners. Subsamples were drawn from sample 2 to examine if there were differences by state. The three subsamples included firearm owners from Minnesota (n = 515), Mississippi (535), and New Jersey (506). Logistic regressions were used to examine the association between frequency of sellers notifying buyers of locks and subsequent locking device use. Linear regressions were used to examine what demographic factors were associated with greater frequency of seller notification of locking devices.

Results
Results indicated a general trend such that more frequent notification of cable locks at the point of purchase was associated with greater likelihood of using locking devices to secure firearms. At the subsample level, these findings were most consistent for Mississippi relative to Minnesota and New Jersey. Exploratory analyses generally indicated those who were younger and those living in more densely populated areas were more likely to be notified about cable locks at the point of purchase.

Conclusions
These findings suggest that interactions about cable locks at the point of firearm purchase has an impact on firearm storage behaviors. Such results indicate that encouraging firearm retailers to have these discussions with those purchasing firearms might be an important strategy for preventing firearm-related fatalities and nonfatal injuries.
Influence of discontinuation of prophylactic antimicrobial agent for trabeculectomy
Authors: Ushio Yuuka , Yoshikawa Hiroshi , Murase Tetsuya , Kataoka Tatsuo , Miyamoto Shohei , Maruko Kazunari , Okamoto Shoko , Shibata Yuuka , Toda Ryotaro , Kiuchi Yoshiaki , Matsuo Hiroaki 
Published: March 2023

Abstract
Background
There is no unified view of the necessity of prophylactic antimicrobial agents in trabeculectomy. Preoperative prophylactic antimicrobial agent injection and cefazolin sodium (CEZ) for trabeculectomy were discontinued at the Hiroshima University Hospital. In this study, we evaluated whether discontinuation of preoperative administration of CEZ in ophthalmology affects the incidence of postoperative infections.

Methods
We retrospectively investigated patient background, concomitant medications, subconjunctival dexamethasone sodium phosphate (DEX) injection at the end of the surgery, and the incidence of infective endophthalmitis within 6 weeks after surgery in the CEZ and non-CEZ groups. We also performed propensity score matching for background matching. Statistical analysis was performed using the Mann-Whitney U-test and Fisher’s exact test.

Results
The incidence of postoperative endophthalmitis was not significantly different between 629 and 751 patients in the CEZ and no-CEZ groups, respectively (0 in the CEZ group and 2 in the no-CEZ group, P = 0.504). More patients in the CEZ group were taking diabetes drugs preoperatively (P = 0.028) and fewer patients were receiving subconjunctival DEX at the end of surgery (P < 0.001) than those in the non-CEZ group. Propensity scores were calculated using the risk factors for postoperative infection as covariates, and matching (580 patients in the CEZ group and 580 patients in the non-CEZ group) showed no significant difference in the incidence of postoperative endophthalmitis (P = 0.500).

Conclusions
There was no significant difference in the incidence of endophthalmitis after trabeculectomy between the CEZ and non-CEZ groups, suggesting a decreased need for CEZ injections before trabeculectomy.