bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Insurance Landscape for Implant- and Autologous-based Breast Reconstruction in the United States
Authors: Boyd Louisa C. , Greenfield Jason A. , Ainapurapu Sravya S. , Skladman Rachel , Skolnick Gary , Sundaramoorthi Durai , Sacks Justin M. 
Published: February 2023

Background:
Insurance coverage of postmastectomy breast reconstruction is mandated in America, regardless of reconstructive modality. Despite enhanced patient-reported outcomes, autologous reconstruction is utilized less than nonautologous reconstruction nationally. Lower reimbursement from Medicare and Medicaid may disincentivize autologous-based reconstruction. This study examines the impact of insurance and sociodemographic factors on breast reconstruction.

Methods:
A retrospective analysis of the Healthcare Cost and Utilization Project National Inpatient Sample Database from 2014 to 2017 was performed. International Classification of Diseases Clinical Modification and Procedure Coding System codes were used to identify patients for inclusion. De-identified sociodemographic and insurance data were analyzed using χ
2, least absolute shrinkage and selection operator regression analysis, and classification trees.

Results:
In total, 31,468 patients were identified for analysis and stratified by reconstructive modality, sociodemographics, insurance, and hospital characteristics. Most patients underwent nonautologous reconstruction (63.2%). Deep inferior epigastric perforator flaps were the most common autologous modality (46.7%). Least absolute shrinkage and selection operator regression identified Black race, urban-teaching hospitals, nonsmoking status, and obesity to be associated with autologous reconstruction. Publicly-insured patients were less likely to undergo autologous reconstruction than privately-insured patients. Within autologous reconstruction, publicly-insured patients were 1.97 (P < 0.001) times as likely to obtain pedicled flaps than free flaps. Black patients were 33% (P < 0.001) less likely to obtain free flaps than White patients.

Conclusions:
Breast reconstruction is influenced by insurance, hospital demographics, and sociodemographic factors. Action to mitigate this health disparity should be undertaken so that surgical decision-making is solely dependent upon medical and anatomic factors.
p16 INK4A drives nonalcoholic fatty liver disease phenotypes in high fat diet fed mice through biliary E2F1/FOXO1/IGF-1 signaling
Authors: Kundu Debjyoti , Kennedy Lindsey , Zhou Tianhao , Ekser Burcin , Meadows Vik , Sybenga Amelia , Kyritsi Konstantina , Chen Lixian , Ceci Ludovica , Wu Nan , Wu Chaodong , Glaser Shannon , Carpino Guido , Onori Paolo , Gaudio Eugenio , Alpini Gianfranco , Francis Heather 
Published: February 2023

Background and Aims:
NAFLD is characterized by steatosis, hepatic inflammation, and fibrosis, which can develop into NASH. Patients with NAFLD/NASH have increased ductular reaction (DR) and biliary senescence. High fat/high cholesterol diet feeding increases biliary senescence, DR, and biliary insulin-like growth factor-1 (IGF-1) expression in mice. p16/IGF-1 converges with fork-head box transcription factor O1 (FOXO1) through E2F1. We evaluated p16 inhibition on NAFLD phenotypes and biliary E2F1/FOXO1/IGF-1 signaling.

Approach and Results:
4-week wild-type (C57BL/6J) male mice were fed a control diet (CD) or high fat/high cholesterol diet and received either p16 or control Vivo Morpholino (VM) by tail vein injection 2× during the 16th week of feeding. We confirmed p16 knockdown and examined: (i) NAFLD phenotypes; (ii) DR and biliary senescence; (iii) serum metabolites; and (iv) biliary E2F1/FOXO1/IGF-1 signaling. Human normal, NAFLD, and NASH liver samples and isolated cholangiocytes treated with control or p16 VM were evaluated for p16/E2F1/FOXO1/IGF-1 signaling. p16 VM treatment reduced cholangiocyte and hepatocyte p16. In wild-type high fat/high cholesterol diet mice with control VM, there were increased (i) NAFLD phenotypes; (ii) DR and biliary senescence; (iii) serum metabolites; and (iv) biliary E2F1/FOXO1/IGF-1 signaling; however, p16 VM treatment reduced these parameters. Biliary E2F1/FOX-O1/IGF-1 signaling increased in human NAFLD/NASH but was blocked by p16 VM. In vitro, p16 VM reduced biliary E2f1 and Foxo1 transcription by inhibiting RNA pol II binding and E2F1 binding at the Foxo1 locus, respectively. Inhibition of E2F1 reduced biliary FOXO1 in vitro.

Conclusion:
Attenuating hepatic p16 expression may be a therapeutic approach for improving NAFLD/NASH phenotypes.
Treatment of chronic hepatitis D with peginterferon lambda—the phase 2 LIMT-1 clinical trial
Authors: Etzion Ohad , Hamid Saeed , Lurie Yoav , Gane Edward J. , Yardeni David , Duehren Sarah , Bader Nimrah , Nevo-Shor Anat , Channa Saleh Muhammad , Cotler Scott J. , Mawani Minaz , Parkash Om , Dahari Harel , Choong Ingrid , Glenn Jeffrey S. 
Published: February 2023

Background and Aims:
HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV.

Approach and Results:
An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35–364); and bilirubin 0.5 mg/dL (0.2–1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation.

Conclusions:
Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.
P4HA2 induces hepatic ductular reaction and biliary fibrosis in chronic cholestatic liver diseases
Authors: Zhang Jun , Lyu Zhuwan , Li Bo , You Zhengrui , Cui Nana , Li You , Li Yikang , Huang Bingyuan , Chen Ruiling , Chen Yong , Peng Yanshen , Fang Jingyuan , Wang Qixia , Miao Qi , Tang Ruqi , Gershwin M. Eric , Lian Min , Xiao Xiao , Ma Xiong 
Published: February 2023

Backgrounds:
Prolyl-4-hydroxylases (P4Hs) are key enzymes in collagen synthesis. The P4HA subunit (P4HA1, P4HA2, and P4HA3) contains a substrate binding and catalyzation domain. We postulated that P4HA2 would play a key role in the cholangiocyte pathology of cholestatic liver diseases.

Methods:
We studied humans with primary biliary cholangitis (PBC) and Primary sclerosing cholangitis (PSC), P4HA2-/- mice injured by DDC, and P4HA2-/-/MDR2-/- double knockout mice. A parallel study was performed in patients with PBC, PSC, and controls using immunohistochemistry and immunofluorescence. In the murine model, the level of ductular reaction and biliary fibrosis were monitored by histology, qPCR, immunohistochemistry, and Western blotting. Expression of Yes1 Associated Transcriptional Regulator (YAP) phosphorylation was measured in isolated mouse cholangiocytes. The mechanism of P4HA2 was explored in RBE and 293T cell lines by using qPCR, Western blot, immunofluorescence, and co-immunoprecipitation.

Results:
The hepatic expression level of P4HA2 was highly elevated in patients with PBC or PSC. Ductular reactive cholangiocytes predominantly expressed P4HA2. Cholestatic patients with more severe liver injury correlated with levels of P4HA2 in the liver. In P4HA2-/- mice, there was a significantly reduced level of ductular reaction and fibrosis compared with controls in the DDC-induced chronic cholestasis. Decreased liver fibrosis and ductular reaction were observed in P4HA2-/-/MDR2-/- mice compared with MDR2-/- mice. Cholangiocytes isolated from P4HA2-/-/MDR2-/- mice displayed a higher level of YAP phosphorylation, resulting in cholangiocytes proliferation inhibition. In vitro studies showed that P4HA2 promotes RBE cell proliferation by inducing SAV1 degradation, eventually resulting in the activation of YAP.

Conclusions:
P4HA2 promotes hepatic ductular reaction and biliary fibrosis by regulating the SAV1-mediated Hippo signaling pathway. P4HA2 is a potential therapeutic target for PBC and PSC.
Effect of respiratory training on respiratory failure secondary to unilateral phrenic nerve injury: A case report
Authors: Li Dawei , Li Zhendong , Zhang Zhiyou , Liu Yueyang , Wang Congcong , Cheng Aixia 
Published: February 2023

Introduction:
Diaphragm is one of the most important respiratory muscles dominated by the phrenic nerve. Phrenic nerve injury would induce a series of clinical symptoms, including respiratory failure. Respiratory training could assist in regular treatment in improving the respiratory function and daily ability of respiratory failure patients.

Case presentation:
A 71-years-old female was enrolled for the disorders of consciousness of 4.5 hours observed by her family and was diagnosed with respiratory failure secondary to unilateral phrenic nerve injury. The patient received basic therapy combined with rehabilitation training, including the training of aspirate muscle, limb resistance, thoracic loosening, aerobic training, electrical stimulation on respiratory nerves, and airway clearance. The combining therapeutic strategy significantly improved the daily ability and respiratory of the patient. The ultrasound showed that after therapy, the diaphragmatic muscles were thickened and the range of diaphragmatic movement was also enhanced. The pulmonary function was also improved after therapy.

Conclusion:
The combination of rehabilitation is suitable for the treatment of respiratory failure patients with clear causes of phrenic nerve injury. For patients with unexplained causes, rehabilitation could also be performed before the diagnosis. Patients with irreversible injury need long-term and family rehabilitation prescriptions.
Adverse reactions and efficacy of camrelizumab in patients with lung adenocarcinoma with high PD-L1 expression: A case report
Authors: Wei Tingting , Wang Zhisheng , Liu Xinlan 
Published: February 2023

Rationale:
Immune checkpoint inhibitors have been rapidly developed for lung cancer therapy and major clinical guidelines have recommended them as the optimal first-line treatment for PD-L1-positive advanced lung cancer. Unfortunately, there is a lack of efficient prediction tools for the occurrence of immune-related adverse events (irAEs) caused by immunotherapy, and there is a lack of real-world data on the processing of irAEs, particularly those occurring in multiple systems simultaneously.

Patient concerns:
We report a 62-year-old male with expectoration who was diagnosed with lung adenocarcinoma with brain and bone metastases.

Diagnoses:
The results of the lung cancer tissue biopsy showed lung adenocarcinoma. Gene detection results of lung cancer tissue biopsy showed that the KRAS gene G12D was mutated and PD-L1 was positive, with a tumor proportion score of 95% (Dako 22C3 IHC platform).

Interventions:
The patient initially received 1 cycle of pemetrexed in combination with cisplatin-based chemotherapy. After the results of PD-L1 testing were reported, he received 1 cycle of camrelizumab immunotherapy in combination with pemetrexed plus cisplatin based chemotherapy.

Outcomes:
Seventeen days after treatment, the patient presented with symptoms such as yellow staining of the sclera and skin, itching throughout the body, dry mouth, and ecchymosis of the skin of the right lower extremity, which continued to worsen. Following treatment with 2 mg/kg methylprednisolone, the patient’s condition continued to deteriorate. IrAEs were controlled after dose escalation to 8 mg/kg in combination with plasma exchange therapy and treatment with multiple doses of mycophenolate ester. The patient then received no treatment for almost 2 months, but examination revealed that the tumor still had a persistent shrinkage reaction.

Lessons:
Camrelizumab has been well tolerated in several studies, but in patients with high PD-L1 expression and a G12D mutation in KRAS, one should be alert to the development of serious or even multisystem immune-related adverse effects. Timely and individualized selection of the hormone dosage is essential for the treatment of immunotherapy-induced multisystem irAEs.
Screening and identification of hub-gene associated with brain metastasis in breast cancer
Authors: Li Xiao-Gang , Niu Chao , Lu Ping , Wan Hong-Wei , Jin Wen-Di , Wang Chun-Xiao , Mao Wen-Yuan , Zhang Zhi-Ping , Zhang Wan-Fu , Li Bo 
Published: February 2023

Background:
The presence of breast cancer in the brain, also known as brain metastasis (BMS), is the primary reason for a bad prognosis in cases of breast cancer. Breast cancer is the most prevalent malignant tumor seen in women in developing nations. At present, there is no effective method to inhibit brain metastasis of breast cancer. Therefore, it is necessary to conduct a systematic study on BMS of breast cancer, which will not provide ideas and sites for follow-up studies on the treatment and inhibition of BMS.

Methods:
In this study, data set GSE43837 was screened from gene expression omnibus database, and then R language tool was used for differential analysis of its expression spectrum, The gene ontology functional enrichment and Kyoto encyclopedia of genes and genomes signal pathway enrichment analyses, as well as the interactive gene retrieval tool for hub-gene analysis, were performed.

Results:
According to the findings, the primary genes linked to breast cancer brain metastases are those that involve interactions between cytokines and their respective receptors and between neuroactive ligands and their respective receptors. The majority of the gene ontology enrichment took place in the extracellular structural tissues, the extracellular matrix tissues, and the second message-mediated signaling. We were able to identify 8 genes that are linked to breast cancer spreading to the brain. The gene score for matrix metallopeptidase1 (MMP-1) was the highest among them, and the genes MMP10, tumor necrosis factor alpha-inducible protein 8, collagen type I alpha 2 chain, vascular cell adhesion molecule 1, and TNF superfamily member 11 were all connected to 1 another in an interaction way.

Conclusions:
There is a possibility that the 8 key genes that were identified in this research are connected to the progression of BMS in breast cancer. Among them, MMP1 is 1 that has the potential to have a role in the diagnosis and treatment of BMS in breast cancer.
Effects of late evening snacks on glucose homeostasis in cirrhotic patients: A meta-analysis
Authors: Chen Ni , Qiu Xinze , Ruan Huaqiang , Huang Jiean , Liu Shiquan 
Published: February 2023

Background:
Insulin resistance and hepatogenic diabetes are common complications in patients with liver cirrhosis. Previous studies have shown that reducing the fasting phase by supplying a late evening snack (LES) is a potential intervention to improve substrate utilization and liver function. However, the underlying mechanisms need to be further elucidated. The purpose of current meta-analysis is to evaluate effects of LES on glucose homeostasis in cirrhotic patients.

Methods:
Electronic databases including PubMed, Web of Science, and major scientific conference sessions were searched without language restriction and carried out on March 1, 2022 with an additional manual search of bibliographies of relevant articles. A total of 4145 studies were identified, and 10 studies were eligible for the meta-analysis, comprising 631 patients (319 in the LES group and 312 in the non-LES group). Subgroup analyses were performed to investigate the effect of LES on cirrhotic patients with or without diabetes.

Results:
Analysis showed that LES intervention had significant effects in cirrhotic patients for glycemic parameters on fasting plasma glucose, fasting insulin, and glycosylated hemoglobin respective effect sizes of −8.7, −0.86, and −0.76. Subgroup result revealed that the effect of LES on fasting plasma glucose is higher in cirrhotic patients with diabetes group than cirrhotic patients without diabetes group, and long-term LES supplementation (>2 months) was more beneficial to maintain glucose homeostasis in cirrhotic patients than that of short-term supplementation (<2 months). LES also had significant effect on nutritional metabolic parameters like including albumin and non-protein respiratory quotient.

Conclusion:
Meta-analysis indicated that LES not only improved malnutrition in cirrhotic patients with or without diabetes but also maintain glucose homeostasis in cirrhotic patients with diabetes. LES is a promising and simple intervention that beneficial to maintain glucose homeostasis in cirrhotic patients.
Understanding the molecular mechanism of Ginkgo Folium-Forsythiae Fructus for cerebral atherosclerosis treatment using network pharmacology and molecular docking
Authors: Zhang Jinfei , Gai Jialin , Ma Hengqin , Tang Jiqin , Yang Chuntao , Zu Guoxiu 
Published: February 2023

Background:
Cerebral atherosclerosis (CA) is a chronic disease caused by multiple infarcts and atrophy causing nerve degenerative syndrome. Ginkgo Folium (GF) and Forsythiae Fructus (FF) have shown positive effects on vascular protection, but their relationship with CA is unclear. This study aimed to identify the potential CA targets and mechanisms of action of GF-FF, using network pharmacology.

Objective:
This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of GF-FF on CA.

Methods:
Using the traditional Chinese medicine systems pharmacology database and analysis platform, components were screened and corresponding targets were predicted using boundary values and Swiss Target Prediction. Using Cytoscape 3.8.0, a network was established between GF-FF components and CA targets. We extracted disease genes and constructed a network of targets based on the protein-protein interaction networks functional enrichment analysis database. Using Metascape, the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes of the enriched targets were determined. AutoDock Vina was used to perform molecular docking.

Results:
Twenty-three active ingredients of GF-FF were confirmed to treat CA, covering 109 targets, of which 48 were CA-related. Luteolin, bicuculline, sesamin, kaempferol, quercetin, and ginkgolide B were the vital active compounds, and EGFR, CYP2E1, CREB1, CYP19A1, PTGS2, PPARG, PPARA, ESR1, MMP9, MAPK14, MAPK8, and PLG were the major targets. The molecular docking showed that these compounds and targets exhibited good intercalation. These 48 protein targets produced effects on CA by modulating pathways such as “apoptosis–multiple species,” “IL-17 signaling pathway,” and “relaxin signaling pathway.”

Conclusions:
As predicted by network pharmacology, GF-FF exerts anti-tumor effects through multiple components and targets for treatment of CA, providing new clinical ideas for CA treatment.
Effects of ulinastatin therapy in emergency severe multiple trauma: A single-center randomized controlled trial
Authors: Xu Haiting , Jiao Wei , Zhang Yunfei , Deng Xiaoyan , Dai Rongrong , Chen Lei 
Published: February 2023

Background:
Severe multiple traumas are one of the most common diseases and carry a significant financial burden with high disability and mortality. There are no effective drugs in the clinical management of severe multiple traumas, and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.

Methods:
The present study explored whether ulinastatin (UTI) can improve the outcome of severe multiple traumas. The present research included patients who were hospitalized in intensive care units after being diagnosed with severe multiple trauma. Patients received UTIs (400,000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were 30-day mortality, multiple organ dysfunction syndrome, inflammatory response, coagulation function, infection, liver function, renal function, and drug-related adverse effects.

Results:
A total of 239 individuals were classified into 2 groups, namely, the placebo group (n = 120) and the UTI group (n = 119). There were no statistically significant differences in baseline clinical data between the 2 groups. The 30-day mortality and multiple organ dysfunction syndrome in the UTI group were remarkably improved compared with those in the placebo group. UTI can protect against hyperinflammation and improve coagulation dysfunction, infection, liver function, and renal function. UTI patients had markedly decreased hospitalization expenditures compared with the placebo group.

Conclusion:
The findings from the present research indicated that UTIs can improve the clinical outcomes of patients with severe multiple traumas and have fewer adverse reactions.
A systematic review of auricular therapy for poststroke cognitive impairment and dementia: A protocol for systematic review and meta-analysis
Authors: Gao Zhaohong , Li Junfeng , Wang Liqin , Li Yan 
Published: February 2023

Background:
Post-stroke cognitive impairment and dementia (PSCID) is the main source of morbidity and mortality after stroke worldwide. It is one consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia after the clinical stroke may contribute to the clinical expression of PSCID, which are prevalent clinical symptoms, especially in the elderly. Current problems in the field of PSCID are related to a lack of harmonization of the classification and definition, deficiency of well-defined diagnosis, deficiency of standardized and objective treatment plans, etc. Auricular therapy can effectively improve the symptoms of patients with PSCID. However, there has been no systematic review of auricular therapy for PSCID. This study aimed to evaluate the efficacy and safety of auricular therapy in patients with PSCID.

Methods:
Before December 2022, a systematic literature search was conducted using the following databases: PubMed, Embase, SinoMed (previously called the Chinese Biomedical Database), Web of Science, Chinese National Knowledge Infrastructure, and Wanfang Database. Review Manager software (version 5.3) will be used for statistical analysis; otherwise, descriptive analysis or subgroup analysis will be conducted. The quality of evidence for outcomes will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach.

Results:
This meta-analysis further confirmed the beneficial effects of auricular therapy in patients with PSCID.

Conclusion:
This study investigated the efficacy and safety of auricular therapy in patients with PSCID, providing clinicians and patients with additional options for this disease.