bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression
Authors: Hu Yue , Zhao Min , Wang Hui , Guo Yang , Cheng Xiaolan , Zhao Tong , Wang Hanqing , Zhang Yafeng , Ma Yong , Tao Weiwei 
Published: August 2023

AbstractThe development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.
Graphical Abstract
Conversion of senescent cartilage into a pro-chondrogenic microenvironment with antibody-functionalized copper sulfate nanoparticles for efficient osteoarthritis therapy
Authors: Wang Xianming , Cai Yu , Wu Cuixi , Liang Jiamin , Tang Kangning , Lin Zefeng , Chen Lingling , Lu Yao , Wang Qing 
Published: August 2023

AbstractThe development of osteoarthritis (OA) correlates with the expansion of senescent cells in cartilage, which contributes to an inflammatory microenvironment that accelerates matrix degradation and hampers cartilage generation. To address OA, we synthesized small copper sulfide nanoparticles functionalized with anti-beta-2-microglobulin antibodies (B2M-CuS NPs) that catalyze the formation of toxic •OH from H2O2 via peroxidase-like activity. These B2M-CuS NPs are specifically targeted to induce apoptosis in senescent chondrocytes while showing no toxicity toward normal chondrocytes. Furthermore, B2M-CuS NPs enhance the chondrogenesis of normal chondrocytes. Thus, B2M-CuS NPs can effectively treat OA by clearing senescent chondrocytes and promoting cartilage regeneration after intra-articular injection into the knee joints of surgery-induced OA mice. This study uses smart nanomaterials to treat OA with a synergistic strategy that both remodels senescent cartilage and creates a pro-chondrogenic microenvironment.
Clinical outcomes of parenchymal-sparing versus anatomic resection for colorectal liver metastases: a systematic review and meta-analysis
Authors: Wang Kun , Liu Yin , Hao Mengdi , Li Huimin , Liang Xiaoqing , Yuan Dajin , Ding Lei 
Published: August 2023

Abstract
Background
The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate their safety and efficacy.

Methods
A systematic review and meta-analysis of short-term perioperative outcomes and long-term oncological outcomes for PSR and AR were performed by searching Pubmed, Embase, the Cochrane Library and Web of Science databases.

Results
Twenty-two studies were considered eligible (totally 7228 patients: AR, n = 3154 (43.6%) vs. PSR, n = 4074 (56.4%)). Overall survival (OS, HR = 1.08, 95% CI: 0.95-1.22, P = 0.245) and disease-free survival (DFS, HR = 1.09, 95% CI: 0.94-1.28, P = 0.259) were comparable between the two groups. There were no significant differences in 3-year OS, 5-year OS, 3-year DFS, 5-year DFS, 3-year liver recurrence-free survival (liver-RFS) and 5-year liver-RFS. In terms of perioperative outcome, patients undergoing AR surgery were associated with prolonged operation time (WMD = 51.48 min, 95% CI: 29.03-73.93, P < 0.001), higher amount of blood loss (WMD = 189.92 ml, 95% CI: 21.39-358.45, P = 0.027), increased intraoperative blood transfusion rate (RR = 2.24, 95% CI: 1.54-3.26, P < 0.001), prolonged hospital stay (WMD = 1.00 day, 95% CI: 0.34-1.67, P = 0.003), postoperative complications (RR = 2.28, 95% CI: 1.88-2.77, P < 0.001), and 90-day mortality (RR = 3.08, 95% CI: 1.88-5.03, P < 0.001). While PSR surgery was associated with positive resection margins (RR = 0.77, 95% CI: 0.61-0.97, P = 0.024), intrahepatic recurrence (RR = 0.90, 95% CI: 0.82-0.98, P = 0.021) and repeat hepatectomy (RR = 0.64, 95% CI: 0.55-0.76, P < 0.001).

Conclusion
Considering relatively acceptable heterogeneity, PSR had better perioperative outcomes without compromising oncological long-term outcomes. However, these findings must be carefully interpreted, requiring more supporting evidence.

Trial registration
PROSPERO registration number: CRD42023445332.
A novel radiographic analysis system for subaxial cervical spine pedicle screw placement
Authors: Ding Baozhi , Zhou Tangjun , Ma Hui , Zhao Jie 
Published: August 2023

Abstract
Background
Precise pedicle screw placement of the subaxial cervical spine is difficult. Not every hospital is equipped with a guidance system that can provide effective help. Computed tomography (CT) scanning is almost a routine preoperative examination for cervical spine surgery in all hospitals. Appropriate measurement and analysis of the CT images could assist optimal cervical pedicle screw placement. The purpose of this study is to propose a new and universal method using computed tomography (CT) morphological parameters analysis to assist optimal cervical pedicle screw placement from C3 to C7.

Methods
A localization system with six parameters was designed based on preoperative CT reconstruction to guide subaxial cervical spine pedicle screw placement. The six parameters were distance from the starting point to the midline [D1], distance from the starting point to the lower edge of the inferior articular process [D2], transverse section angle [TSA], sagittal section angle [SSA], pedicle width [PW], and pedicle height [PH]. The six parameters were analyzed in 53 participants.

Results
Combining D1 and D2 could localize the entrance of the pedicle screw, and we concluded that D1 and TSA and D2 and SSA could be a new standard for determination of the transverse and sagittal orientation of the pedicle screw. The six parameters were closely related to the patient’s gender, height, and weight. PH and PW were linearly correlated and could guide selection of the appropriate pedicle screw. SSA was an independent parameter of the relevant vertebral body, and changes in SSA had nothing to do with the curvature or posture of the cervical spine.

Conclusions
Understanding and applying the six-parameter localization system are essential for achieving accurate and optimal pedicle screw placement in subaxial cervical spine, regardless of cervical sagittal alignment.
Specific detection of tau seeding activity in Alzheimer’s disease using rationally designed biosensor cells
Authors: Lathuiliere Aurelien , Jo Youhwa , Perbet Romain , Donahue Cameron , Commins Caitlin , Quittot Noé , Fan Zhanyun , Bennett Rachel E. , Hyman Bradley T. 
Published: August 2023

Abstract
Background
The prion-like propagation of tau in neurodegenerative disorders implies that misfolded pathological tau can recruit the normal protein and template its aggregation. Here, we report the methods for the development of sensitive biosensor cell lines for the detection of tau seeding activity.

Results
We performed the rational design of novel tau probes based on the current structural knowledge of pathological tau aggregates in Alzheimer’s disease. We generated Förster resonance energy transfer (FRET)-based biosensor stable cell lines and characterized their sensitivity, specificity, and overall ability to detect bioactive tau in human samples. As compared to the reference biosensor line, the optimized probe design resulted in an increased efficiency in the detection of tau seeding. The increased sensitivity allowed for the detection of lower amount of tau seeding competency in human brain samples, while preserving specificity for tau seeds found in Alzheimer’s disease.

Conclusions
This next generation of FRET-based biosensor cells is a novel tool to study tau seeding activity in Alzheimer’s disease human samples, especially in samples with low levels of seeding activity, which may help studying early tau-related pathological events.
Reconstruction of the last bacterial common ancestor from 183 pangenomes reveals a versatile ancient core genome
Authors: Hyun Jason C. , Palsson Bernhard O. 
Published: August 2023

Abstract
Background
Cumulative sequencing efforts have yielded enough genomes to construct pangenomes for dozens of bacterial species and elucidate intraspecies gene conservation. Given the diversity of organisms for which this is achievable, similar analyses for ancestral species are feasible through the integration of pangenomics and phylogenetics, promising deeper insights into the nature of ancient life.

Results
We construct pangenomes for 183 bacterial species from 54,085 genomes and identify their core genomes using a novel statistical model to estimate genome-specific error rates and underlying gene frequencies. The core genomes are then integrated into a phylogenetic tree to reconstruct the core genome of the last bacterial common ancestor (LBCA), yielding three main results: First, the gene content of modern and ancestral core genomes are diverse at the level of individual genes but are similarly distributed by functional category and share several poorly characterized genes. Second, the LBCA core genome is distinct from any individual modern core genome but has many fundamental biological systems intact, especially those involving translation machinery and biosynthetic pathways to all major nucleotides and amino acids. Third, despite this metabolic versatility, the LBCA core genome likely requires additional non-core genes for viability, based on comparisons with the minimal organism, JCVI-Syn3A.

Conclusions
These results suggest that many cellular systems commonly conserved in modern bacteria were not just present in ancient bacteria but were nearly immutable with respect to short-term intraspecies variation. Extending this analysis to other domains of life will likely provide similar insights into more distant ancestral species.
Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII)
Authors: Ren Zhenyu , Shi Qiyang , Xu Simin , Xu Jiahui , Yin Yi , Lin Zhijie , Xu Sui , Ma Xiaoqin , Liu Yaobao , Zhu Guoding , He Xinlong , Lu Jingyuan , Li Yinyue , Zhang Wenwen , Liu Jiali , Yang Yun , Han Eun-Taek , Cao Jun , Lu Feng 
Published: August 2023

Abstract
Background
Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps.

Methods
A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry.

Results
Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L− T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII‑immunized mice.

Conclusions
PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities.

Graphical Abstract
Bacterial ventriculoperitoneal shunt infections: changing trends in antimicrobial susceptibility, a 7-year retrospective study from Pakistan
Authors: Akram Asif Amina , Mahmood Khalid , Riaz Saba , McHugh Timothy , Sultan Sikander 
Published: August 2023

Abstract
Background
Ventriculoperitoneal (VP) shunt infections in adults represent a severe complication and make treatment more challenging. Therefore, drug susceptibility patterns are crucial for therapeutic decisions and infection control in neurosurgical centers. This 7-year retrospective study aimed to identify the bacteria responsible for adult VP shunt infections and determine their drug susceptibility patterns.

Methods
This single-center study was performed from 2015 to 2021 in Lahore, Pakistan, and included CSF cultures from VP shunt infections. Demographic data, causative organisms, and antimicrobial susceptibility testing results were collected. Multivariate analysis of variance (MANOVA) and two-sample t-tests were used to analyze and compare the antibiotic sensitivity trends over the study period.

Results
14,473 isolates recovered from 13,937 CSF samples of VP shunt infections were identified and analyzed for their susceptibility patterns to antimicrobials. The proportion of Gram-negative and Gram-positive bacteria were 11,030 (76%) and 3443 (24)%, respectively. The predominant bacteria were Acinetobacter species (n = 5898, 41%), followed by Pseudomonas species (n = 2368, 16%) and coagulase-negative Staphylococcus (CoNS) (n = 1880, 13%). 100% of Staphylococcus aureus (S.aureus) and CoNS were sensitive to vancomycin and linezolid (n = 2580). However, 52% of S. aureus (719/1,343) were methicillin-resistant Staphylococcus aureus (MRSA). Acinetobacter showed maximum sensitivity to meropenem at 69% (2759/4768). Pseudomonas was 80% (1385/1863 sensitive to piperacillin-tazobactam, Escherichia coli (E. coli) showed 72% to amikacin (748/1055), while Klebsiella spp. was 57% (574/1170) sensitive to piperacillin-tazobactam. The sensitivity of piperacillin-tazobactam and meropenem for Gram-negative bacteria decreased significantly (p < 0.05) over 7 years, with 92.2% and 88.91% sensitive in 2015 and 66.7% and 62.8% sensitive in 2021, respectively.

Conclusion
The significant decrease in the effectiveness of carbapenem and beta-lactam/beta-lactamase inhibitor combination drugs for the common Gram-negative causative agents of VP shunt infections suggests that alternative antibiotics such as colistin, fosfomycin, ceftazidime/avibactam, ceftolozane/tazobactam, and tigecycline should be considered and in consequence included in testing panels. Additionally, it is recommended to adopt care bundles for the prevention of VP shunt infection.
Identification of GRIN2D as a novel therapeutic target in pancreatic ductal adenocarcinoma
Authors: Wang Jiatong , Wong Chi Hin , Zhu Yinxin , Yao Xiaoqiang , Ng Kelvin K C , Zhou Chengzhi , To Ka Fai , Chen Yangchao 
Published: August 2023

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a dismal prognosis, and despite significant advances in our understanding of its genetic drivers, like KRAS, TP53, CDKN2A, and SMAD4, effective therapies remain limited. Here, we identified a new therapeutic target GRIN2D and then explored its functions and mechanisms in PDAC progression.

Methods
We performed a genome-wide RNAi screen in a PDAC xenograft model and identified GRIN2D, which encodes the GluN2D subunit of N-methyl-D-aspartate receptors (NMDARs), as a potential oncogene. Western blot, immunohistochemistry, and analysis on Gene Expression Omnibus were used for detecting the expression of GRIN2D in PDAC. Cellular experiments were conducted for exploring the functions of GRIN2D in vitro while subcutaneous and orthotopic injections were used in in vivo study. To clarify the mechanism, we used RNA sequencing and cellular experiments to identify the related signaling pathway. Cellular assays, RT-qPCR, and western blot helped identify the impacts of the NMDAR antagonist memantine.

Results
We demonstrated that GRIN2D was highly expressed in PDAC cells, and further promoted oncogenic functions. Mechanistically, transcriptome profiling identified GRIN2D-regulated genes in PDAC cells. We found that GRIN2D promoted PDAC progression by activating the p38 MAPK signaling pathway and transcription factor CREB, which in turn promoted the expression of HMGA2 and IL20RB. The upregulated GRIN2D could effectively promote tumor growth and liver metastasis in PDAC. We also investigated the therapeutic potential of NMDAR antagonism in PDAC and found that memantine reduced the expression of GRIN2D and inhibited PDAC progression.

Conclusion
Our results suggested that NMDA receptor GRIN2D plays important oncogenic roles in PDAC and represents a novel therapeutic target.
Precision education via timely intervention in K-12 computer programming course to enhance programming skill and affective-domain learning objectives
Authors: Lee Hsin-Yu , Lin Chia-Ju , Wang Wei-Sheng , Chang Wei-Cyun , Huang Yueh-Min 
Published: August 2023

Abstract
Background
In the realm of Science, Technology, Engineering, and Mathematic (STEM) education, computer programming stands as a vital discipline, amalgamating cross-disciplinary knowledge and fostering the capacity to solve real-world problems via fundamental concepts and logical methodologies inherent to computer science. Recognizing the important of computer programming, numerous countries have mandated it as a compulsory course to augment the competitiveness of K-12 learners. Nevertheless, the inherent complexity of computer programming for K-12 learners often goes unacknowledged. Constraints imposed by the course format, coupled with a low instructor–learner ratio, frequently inhibit learners’ ability to resolve course-related issues promptly, thereby creating difficulties in the affective domain. While precision education tools do exist to ascertain learners’ needs, they are largely research-oriented, thereby constraining their suitability for deployment in pragmatic educational settings. Addressing this issue, our study introduces the precision education-based timely intervention system (PETIS), an innovative tool conceived to enhance both programming skills and affective learning in K-12 learners. Our research investigates the influence of PETIS on learners’ performance and evaluate its efficacy in facilitating computer programming education in K-12 environments.

Results
Quantitative results demonstrate that the application of the precision education-based timely intervention system (PETIS) proposed by this research significantly improves programming skills and affective-domain learning objectives for K-12 learners. Similarly, qualitative results indicate that PETIS is beneficial for both teaching and learning in K-12 computer programming courses.

Conclusions
These results not only confirm that timely intervention and feedback improve K-12 learners’ programming skills and affective-domain learning objectives in computer programming courses, but also yield implications as to the feasibility of applying precision education in real-world STEM scenarios.
Strangulated bowel obstruction caused by an ileo-ileal knot: a rare case report
Authors: Umetsu Satoko , Shibata Shigeru , Akasaka Harue , Tsutsumi Shinji , Uchida Chiaki , Ogasawara Hirokazu 
Published: August 2023

Abstract
Background
Intestinal knot formation is a condition wherein two segments of the intestine are knotted together; however, reports of small-intestinal ileo-ileal knot formation are rare.

Case presentation
The patient was a 62-year-old Asian male with a history of endoscopic colorectal adenoma resection and a spontaneous pneumothorax. The patient had no history of a laparotomy. He consulted his local doctor with the chief complaint of abdominal pain and was admitted to our hospital with suspicion of an acute abdomen. The abdomen had muscular guarding with tenderness and rebound tenderness. Contrast-enhanced computed tomography (CT) showed torsion of the mesentery of the small intestine with poor contrast filling. The patient was referred to our department with strangulated bowel obstruction and underwent an emergency laparotomy. Intraoperative findings revealed that two segments of the ileum were wrapped around each other to form a knot, and the strangulated small bowel was necrotic. After the release of the knot, partial resection of the small intestine was performed from 220 cm distal to the ligament of Treitz to 80 cm proximal to the cecum. The patient had a good postoperative course and was discharged on the 11th postoperative day.

Conclusion
Ileo-ileal knots should be considered as part of the differential diagnosis when treating strangulated bowel obstruction.
Impact of Overtraining on Cognitive Function in Endurance Athletes: A Systematic Review
Authors: Symons Isabella K. , Bruce Lyndell , Main Luana C. 
Published: August 2023

Abstract
Background
Endurance sports require significant training loads to elicit the desired training effects on an athlete’s body. However, if adequate recovery is not provided, overtraining may occur, with corresponding decrements in performance. As such, there is a need for measures that can be tracked, to monitor athlete adaptation to training loads, and provide early warning of possible maladaptation. The aim of this review was to determine if a relationship exists between overtraining and cognitive function in endurance athletes.

Methods
A systematic search of AMED, MEDLINE, SPORTDiscus and APA PsycINFO was conducted. Eligibility criteria included original peer reviewed research, written in English, published between January 2000 and May 2022, and using human participants. Of the 221 articles screened, a total of seven studies met the inclusion criteria and were included in this review.

Results
The findings of the review suggest that there is a relationship between overtraining and cognitive function with all seven studies finding that cognitive performance declined in response to athletes becoming overreached or overtrained. These studies found that reaction time (as measured by Stroop colour test) increased in response to both overreaching and overtraining.

Conclusions
Cognitive function tests such as the Stroop Colour Test could be included as part of a broader programme for monitoring athlete adaptation to training.