bluuebunny/crossref_metadata_2025_split huggingface dataset:
To corset or not to corset after lumbar spine fixation surgery?: A prospective randomized clinical trial and literature review
Authors: Chen Yin Ju , Yang Jen Tsung , Lin Martin Hsiu Chu , Huang Wei Chao 
Published: April 2024

Purpose:
Orthosis after lumbar fusion surgery is common. However, the evidence for benefit remains to be determined, especially in tropical areas with heavy workers. To investigate postoperative orthosis and whether it affects pain improvement, quality of life, and fusion rate.

Method:
From May 2021 to May 2022, this single-center prospective randomized clinical trial enrolled 110 patients. We excluded 9 patients, and 101 people were analyzed finally. Corset group, in which participants used a corset for 3 months postoperatively; Non-corset group, in which participants didn’t wear any orthosis. ODI and VAS scale were recorded before the surgery: 2 weeks, 1 month, 3 months, half a year, and 1 year postoperatively. The lumbar X-ray was done before the surgery, 6 months postoperatively. All complications in 1 year were recorded.

Results:
Significant decrease in VAS score in the non-corset group since post-operation day 5 (corset group 3.44 ± 1.77, non-corset group 3.36 ± 1.75, P = .0093) during admission, and also a decrease in admission duration (corset group 11.08 ± 2.39, non-corset group 9.55 ± 1.75, P = .0004) were found. There was a significantly better ODI score in the non-corset group since post-operation 1 month, while in the corset group until post-operation 3 months. Both groups had no significant difference in satisfaction, complication rates, and X-ray results, such as fusion, angular rotation, sagittal transition, and slip in the neutral position.

Conclusion:
After the transpedicular screw fixation with posterolateral fusion surgery for degenerative spondylolisthesis, non-orthosis is a safe strategy. It can reduce the admission duration and has the trend for better functional outcomes.
Efficacy and safety of tyrosine kinase inhibitors for advanced metastatic thyroid cancer: A systematic review and network meta-analysis of randomized controlled trials
Authors: Zhao Mingjian , Li Ruowen , Song Zhimin , Miao Chengxu , Lu Jinghui 
Published: April 2024

Background:
Tyrosine kinase inhibitors (TKIs) have been approved for treating patients with clinically advanced metastatic thyroid cancer. However among the many TKIs, it remains unknown which regimen is the best choice for these patients.

Methods:
We conducted a systematic review and network meta-analysis to compare the survival benefits and efficacy of the available first-line regimens. We conducted an active search for phase II, III, or IV randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to compare the effects of at least 2 drugs in the systemic treatment of advanced or metastatic thyroid cancer up to May 2023. The network meta-analysis model was adjusted using Bayesian Network model. Twelve trials with 2535 patients were included in our meta-analysis. The overall survival (OS), progression-free survival (PFS), and serious adverse events (SAEs) were taken as reference indicators. We also performed subgroup analyses of OS and PFS in medullary thyroid cancer (MTC) and radioiodine-refractory differentiated thyroid cancer (RR-DTC) to explore the variations of TKIs in different groups.

Results:
As a result, apatinib had the best effect on overall survival (OS) (hazards ratio [HR] = 0.42, 95% confidence interval [CI] = 0.18–0.98), lenvatinib 18 mg/d has the best effect on progression-free survival (PFS) (HR = 0.13, 95% CI = 0.064–0.27), and cabozantinib 60 mg/d has the best safety profile.

Conclusions:
Our network meta-analysis showed that we believe that cabozantinib has the potential to become a widely used drug in clinical practice.
Bilateral sinonasal inverted papillomas originating from both sides of the frontal sinus and the left lamina papyracea: A case report
Authors: Li Yang , Ma Dengdian 
Published: April 2024

Rationale:
The present investigation documented a case of bilateral sinonasal inverted papilloma (SNIP) that arose from both sides of the frontal sinus and ethmoid sinus. The occurrence of bilateral involvement of the nasal cavities and frontal sinus is rather infrequent.

Patient concerns:
Informed consent was obtained from the patient.

Diagnosis:
Bilateral SNIP.

Interventions:
The tumor was completely removed by Draf III endoscopic resection complemented by an external eyebrow arch approach, and the postoperative recovery was uneventful.

Outcomes:
The purpose of this paper is to present a comprehensive reference for the management of bilateral SNIP that affects the frontal sinuses.

Lessons:
This study addresses the staging and surgical management of bilateral SNIP, along with a review of the factors contributing to its recurrence. The recommended treatment method involves applying the Draf III technique combined with an external nasal approach.
A relatively rare traditional Chinese medicine pattern of primary Sjögren syndrome: A case report
Authors: Chen Qiang , Chen Xinru , Zhu Yuqing , Yu Xiali 
Published: April 2024

Rationale:
This report presents a unique case of a patient diagnosed with Primary Sjögren’s syndrome and a relatively rare traditional Chinese medicine pattern, known as the combined cold and heat pattern and cold-dampness syndrome. The patient’s condition was successfully managed using Chinese herbal medicine, specifically the modified Da-Chai-Hu decoction and Linggui Zhugan decoction.

Patient concerns:
A 56-year-old woman had chronic dry eye and mouth for over 10 years. She was initially managed with traditional Chinese herbal medicine (TCHM) prescriptions, including the Zengye decoction, but the therapeutic effects were unsatisfactory. As the disease progressed, she was diagnosed with an anxiety disorder due to symptoms of vexation and insomnia. Treatment with alprazolam and venlafaxine failed to alleviate these symptoms. Recently, her general condition gradually worsened, with symptoms including a bitter taste in her mouth, dizziness, hot flashes, chills, poor appetite, chest discomfort, and constipation.

Diagnoses:
After a series of examinations, including a Schirmer test and labial gland biopsy, she was diagnosed with Sjögren’s syndrome.

Interventions:
Despite regular treatment with pilocarpine, sodium hyaluronate eye drops, venlafaxine, and alprazolam, the dry mouth symptoms intensified. Consequently, she sought further intervention through the TCHM.

Outcomes:
After 8 weeks of treatment with the modified Da-Chai-Hu decoction and Linggui Zhugan decoction, she reported a significant improvement in her dryness-related symptoms and sleep quality.

Lessons:
This case report demonstrates that TCHM can effectively treat Primary Sjögren’s syndrome, and should be considered for broader applications. Furthermore, this underscores the importance of tailoring treatment formulas to patients by identifying their specific syndrome differentiation in a clinical setting.
Risk factors for postoperative bleeding following endoscopic submucosal dissection in early gastric cancer: A systematic review and meta-analysis
Authors: Gu Yuanbo , Zhao Shuchang 
Published: April 2024

Background:
Early gastric cancer (EGC) presents a significant challenge in surgical management, particularly concerning postoperative bleeding following endoscopic submucosal dissection. Understanding the risk factors associated with postoperative bleeding is crucial for improving patient outcomes.

Methods:
Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review and meta-analysis were conducted across PubMed, Embase, Web of Science, and the Cochrane Library without publication date restrictions. The inclusion criteria encompassed observational studies and randomized controlled trials focusing on EGC patients undergoing endoscopic submucosal dissection and their risk factors for postoperative bleeding. The Newcastle-Ottawa Scale was utilized for quality assessment. The effect size was calculated using random or fixed-effects models based on the observed heterogeneity. We assessed the heterogeneity between studies and conducted a sensitivity analysis.

Results:
In our meta-analysis, 6 studies involving 4868 EGC cases were analyzed. The risk of postoperative bleeding was notably increased with intraoperative ulcer detection (odds ratio: 1.97, 95% confidence interval [CI]: 1.03–3.76, I
2 = 61.0%, P = .025) and antithrombotic medication use (odds ratio: 2.02, 95% CI: 1.16–3.51, I
2 = 57.2%, P = .039). Lesion resection size showed a significant mean difference (5.16, 95% CI: 2.97–7.98, P < .01), and longer intraoperative procedure time was associated with increased bleeding risk (mean difference: 11.69 minutes, 95% CI: 1.82–26.20, P < .05). Sensitivity analysis affirmed the robustness of these findings, and publication bias assessment indicated no significant bias.

Conclusions:
In EGC treatment, the risk of post-endoscopic submucosal dissection bleeding is intricately linked to factors like intraoperative ulcer detection, antithrombotic medication use, the extent of lesion resection, and the length of the surgical procedure. These interwoven risk factors necessitate careful consideration and integrated management strategies to enhance patient outcomes and safety in EGC surgeries.
Diagnostic value of contrast-enhanced ultrasound in the diagnosis of papillary thyroid microcarcinoma: A systematic review and meta-analysis
Authors: Ding Yan , Peng Yulan , Zhang Jing , Pan Xueqin , Huang Xu , Zhang Chun-Quan 
Published: April 2024

Background:
Using meta-analysis to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in the diagnosis of papillary thyroid microcarcinoma (PTMC).

Methods:
For this systematic review and meta-analysis, we searched PubMed, Cochrane Library, Web of Science, WanFang Data, VPCS Data, and China National Knowledge Infrastructure electronic databases for diagnostic studies on PTMC by CEUS from January 2013 to November 2022. Data were not available or incomplete such as case reports, nonhuman studies, etc, were excluded. Random-effects meta-analyses were used to evaluate the diagnostic accuracy of CEUS in diagnosing PTMC. The quality of the evidence was assessed with the QUADAS-2 scale. This study is registered on PROSPERO, number CRD42023409417.

Results:
Of 1064 records identified, 33 were eligible. The results showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CEUS in diagnosing PTMC were 0.84 (95% confidence interval [CI] = 0.83–0.86), 0.82 (95% CI = 0.80–0.83), 3.90 (95% CI = 3.23–4.72), 0.21 (95% CI = 0.18–0.25), and 20.01 (95% CI = 14.97–26.74), respectively, and the area under the summary receiver operating characteristic curve was 0.8930 (the Q index was 0.8239). The Deek funnel plot indicated publication bias (P ˂.01).

Conclusion:
This meta-analysis provides an overview of diagnostic accuracy of CEUS in diagnosing PTMC which indicates CEUS has a good diagnostic value for PTMC. The limitations of this study are publication bias and strong geographical bias.
Reduced selection during sweeps lead to adaptive momentum on rugged landscapes
Authors: Bohm Clifford , Ragusa Vincent R. , Ofria Charles , Lenski Richard E. , Adami Christoph 
Published: April 2024

AbstractEvolutionary theory seeks to explain the remarkable diversity and adaptability of life on Earth. Current theory offers substantial explanatory power, but it overlooks important transient dynamics that are prominent only when populations are outside equilibrium, such as during selective sweeps. We identify a dynamic that we call “adaptive momentum” whereby lineages with a selective advantage can temporarily sustain more deleterious mutations. This reduction in the strength of purifying selection allows populations to explore fitness valleys that are usually too costly to enter, potentially leading to the discovery of otherwise inaccessible fitness peaks. Using mathematical and agent-based simulations, we demonstrate adaptive momentum and show how periods of disequilibrium become windows of enhanced adaptation. Genetic exploration can occur during these windows without requiring mechanisms such as changing environments or complex landscapes. Adaptive momentum provides a simple potential explanation for bursts of rapid evolution observed in nature, including in pathogens such as SARS-CoV-2 and cancers. (152 words)
Defective Homologous Recombination and Genomic Instability Predict Increased Responsiveness to Carbon Ion Radiotherapy in Pancreatic Cancer
Authors: Sishc Brock J. , Saha Janapriya , Polsdofer Elizabeth , Ding Lianghao , Lu Huiming , Wang Shih-Ya , Swancutt Katy L. , Nicholson James H. , Facoetti Angelica , Pompos Arnold , Ciocca Mario , Aguilera Todd A. , Story Michael D. , Davis Anthony J. 
Published: April 2024

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is inherently resistant to conventional chemo-and radiation-therapy. However, clinical trials showed that carbon ion radiotherapy (CIRT) with concurrent gemcitabine can be effective for treating unresectable locally advanced PDAC. In this study, we aimed to determine features that could identify patients who would benefit most from CIRT. A panel of human PDAC cell lines with various genetic backgrounds was leveraged to determine whether a subset could be identified that preferentially responds to CIRT. The cell lines displayed a differential response to CIRT as compared to γ-rays as measured by relative biological effectiveness (RBE) calculated at 10% survival, which ranged from 1.96 to 3.04. Increased radiosensitivity correlated with decreased DNA double strand break (DSB) repair as measured by γH2AX foci resolution. We determined that the cell lines most sensitive to CIRT are defective in the homologous recombination (HR) DSB repair pathway and/or have high genomic instability due to elevated replication stress. Next, this knowledge was utilized to assess whether the HR pathway could be targeted to potentiate CIRTin vitro. It was determined that pretreating a radioresistant PDAC cell line with the HR inhibitor, B02, resulted in a marked increase in sensitivity to CIRT when treated with high linear energy transfer (LET) radiation in the spread-out Bragg peak (74.1-89.3 keV/μm) but not at the entry LET (13.0-16.4 keV/μm)in vitroas opposed to that seen with a NHEJ inhibitor. These data suggest a greater therapeutic index with the combination therapy in the tumor over normal tissues based on LET distribution. These data support the notion that PDAC tumors with defects in HR and/or those with high inherent replication stress respond to CIRT without the concern for excessive normal tissue toxicity. With the advent of agents targeting HR, the difference in tumor cell response in the entry region vs within the SOBP based upon the respective LETs of those regions of the beam profile, will be superior to agents that target NHEJ.
Paradigms of convergent evolution in enzymes
Authors: Riziotis Ioannis G. , Kafas Jenny C. , Ong Gabriel , Borkakoti Neera , Ribeiro Antonio J.M. , Thornton Janet M. 
Published: April 2024

AbstractThere are many occurrences of enzymes catalysing the same reaction but having significantly different structures. Leveraging the comprehensive information on enzymes stored in the Mechanism and Catalytic Site Atlas (M-CSA), we present a collection of 38 cases for which there is sufficient evidence of functional convergence without an evolutionary link. For each case, we compare enzymes which have identical Enzyme Commission numbers (i.e. catalyse the same reaction), but different identifiers in the CATH data resource (i.e. different folds). We focus on similarities between their sequence, structure, active site geometry, cofactors and catalytic mechanism. These features are then assessed to evaluate whether all the evidence on these structurally diverse proteins supports their independent evolution to catalyse the same chemical reaction. Our approach combines literature information with knowledge-based computational resources from, amongst others, M-CSA, PDBe and PDBsum, supported by tailor made software to explore active site structure and assess mechanism similarity. We find that there are multiple varieties of convergent functional evolution observed to date and it is necessary to investigate sequence, structure, active site geometry and enzyme mechanisms to describe such convergence accurately.
ACSS2 contributes to transcriptional regulation in Cajal-Retzius cells in a mouse model of Alzheimer’s disease
Authors: Egervari Gabor , Alexander Desi C. , Donahue Greg , Huang Hua , Hogan Connor , Mendoza Mariel , Garcia Benjamin A. , Bonini Nancy M. , Berger Shelley L. 
Published: April 2024

ABSTRACTDysregulation of histone acetylation in the brain has emerged as a major contributor to human Alzheimer’s disease (AD). The mechanisms by which these protective or risk-conferring epigenetic marks are established and maintained are under intense investigation. ACSS2 (Acetyl-CoA Synthetase 2) is a key metabolic enzyme that is chromatin-associated in neurons. ACSS2 is recruited to specific promoters and generates a local pool of acetyl-CoA from acetate, thereby fueling histone acetylation and driving the expression of neuronal genes that regulate learning and memory. Here, we examine the contribution of ACSS2-mediated histone acetylation to AD-related molecular and behavioral outcomes. Using a mouse model of human pathological AD-Tau injection, we show that loss of ACSS2 exacerbates Tau-related memory impairments, while dietary supplementation of acetate rescues learning in an ACSS2-dependent manner. Combining state-of-the-art proteomic and genomic approaches, we demonstrate that this effect is accompanied by ACSS2-dependent incorporation of acetate into hippocampal histone acetylation, which facilitates gene expression programs related to learning. Further, we identify Cajal-Retzius neurons as a critical hippocampal neuronal population affected, exhibiting the largest epigenetic and transcriptional dysregulation. Overall, these results reveal ACSS2 as a key neuroprotective metabolic enzyme, dysregulation of which might play an important role in the etiology of human AD, and guide the development of future therapies for AD and related dementia.
IL-1RA Disrupts ATP Activation of P2RX7 in Human Monocyte-Derived Microglia-like Cells
Authors: Heavener Kelsey , Kabra Khushbu , Yidenk Maedot , Bradshaw Elizabeth 
Published: April 2024

AbstractThe immune system has a dynamic role in neurodegenerative diseases, and purinergic receptors allow immune cells to recognize neuronal signaling, cell injury, or stress. Purinergic Receptor 7 (P2RX7) can modulate inflammatory cascades and its expression is upregulated in Alzheimer’s disease (AD) brain tissue. P2RX7 expression is enriched in microglia, and elevated levels are found in microglia surrounding amyloid-beta plaques in the brain. While P2RX7 is thought to play a role in neurodegenerative diseases, how it modulates pathology and disease progression is not well understood. Here, we utilize a human monocyte-derived microglia-like cell (MDMi) model to interrogate P2RX7 activation and downstream consequences on microglia function. By using MDMi derived from human donors, we can examine how human donor variation impacts microglia function. We assessed P2RX7-drivenIL1βandIL18production and amyloid-beta peptide 1-42 (Aβ1-42) uptake levels. Our results show that ATP-stimulation of MDMi triggers upregulation ofIL1βandIL18expression. This upregulation of cytokine gene expression is blocked with the A740003 P2RX7 antagonist. We find that high extracellular ATP conditions also reduced MDMi capacity for Aβ1-42 uptake, and this loss of function is prevented through A740003 inhibition of P2RX7. In addition, pretreatment of MDMi with IL-1RA limited ATP-drivenIL1βandIL18gene expression upregulation, indicating that ATP immunomodulation of P2RX7 is IL-1R dependent. Aβ1-42 uptake was higher with IL-1RA pretreatment compared to ATP treatment alone, suggesting P2RX7 regulates phagocytic engulfment through IL-1 signaling. Overall, our results demonstrate that P2RX7 is a key response protein for high extracellular ATP in human microglia-like cells, and its function can be modulated by IL-1 signaling. This work opens the door to future studies examining anti-IL-1 biologics to increase the clearance of amyloid-beta.
Synergistic innate immune activation and anti-tumor immunity through combined STING and TLR4 stimulation
Authors: Higgs Emily F. , Gajewski Thomas F. 
Published: April 2024

AbstractPrevious work has shown that innate immune sensing of tumors involves the host STING pathway, which leads to IFN-β production, dendritic cell (DC) activation, and T cell priming against tumor antigens. This observation has led to the development of STING agonists as a potential cancer therapeutic. However, despite promising results in mouse studies using transplantable tumor models, clinical testing of STING agonists has shown activity in only a minority of patients. Thus, further study of innate immune pathways in anti-tumor immunity is paramount. Innate immune activation in response to a pathogen rarely occurs through stimulation of only one signaling pathway, and activating multiple innate immune pathways similar to a natural infection is one possible strategy to improve the efficacy of STING agonists. To test this, we performed experiments with the STING agonist DMXAA alone or in combination with several TLR agonists. We found that LPS + DMXAA induced significantly greater IFN-β transcription than the sum of either agonist alone. To explain this synergy, we assayed each step of STING pathway signaling. LPS did not increase STING protein aggregation, IRF3 phosphorylation, or IRF3 nuclear translocation beyond what occurred with DMXAA alone. However, since the IFN-β promoter also includes NF-κB binding sites, we additionally examined the NF-κB pathway. In fact, LPS increased the phosphorylation and nuclear translocation of the NF-κB subunit p65, and NF-κB signaling was required for the observed synergy. Intratumoral injection of suboptimal doses of LPS + DMXAA resulted in significantly improved tumor control of B16 melanoma in vivo compared to either agonist alone. Our results suggest that combinatorial signaling through TLR4 and STING results in optimal innate signaling via co-involvement of NF-κB and IRF3, and that combined engagement of these two pathways has therapeutic potential.