bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between antithrombotic therapy and mortality in patients hospitalized for COVID‑19
Authors: Wang Xing , Chen Wuqian , Guo Jiulin , Qiu Xingyu , You Chao , Ma Lu 
Published: January 2024

Abstract
Background
The prothrombotic state is a common abnormality in patients with coronavirus disease 2019 (COVID-19). However, there is controversy over the use of anticoagulants, especially oral anticoagulants (OAC) due to limited studies. We sought to evaluate the association between antithrombotic therapy on mortality and clinical outcomes in patients hospitalized for COVID-19 through propensity score matching (PSM) analysis.

Methods
A retrospective cohort study was performed to include adult patients with COVID-19 in a university hospital. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and acute kidney injury (AKI) during hospitalization. PSM was used as a powerful tool for matching patients’ baseline characteristics. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated from the models.

Results
Of 4,881 COVID-19 patients during the study period, 690 (14.1%) patients received antithrombotic therapy and 4,191 (85.9%) patients were under no antithrombotic therapy. After adjustment with multivariate regression analysis, patients receiving OAC, compared with those who did not receive any antithrombotic therapy, had significantly lower odds for in-hospital mortality (aOR: 0.46. 95% CI: 0.24 to 0.87; P= 0.017). PSM analysis observed similar results (aOR: 0.35. 95% CI: 0.19 to 0.61; P< 0.001). Moreover, in critically ill patients who received mechanical ventilation, antithrombotic treatment (aOR: 0.54. 95% CI: 0.32 to 0.89; P= 0.022) was associated with reduced risk of mortality.

Conclusions
The application OACs was associated with reduced hospital mortality and mechanical ventilation requirement in COVID-19 patients. Besides, antithrombotic treatment was associated with a reduction in in-hospital mortality among critically ill COVID-19 patients who required mechanical ventilation.
SB431542 partially inhibits high glucose-induced EMT by restoring mitochondrial homeostasis in RPE cells
Authors: Cao Jingjing , Jiao Mingfei , Kou Zhenyu , Han Feifei , Dong Lijie 
Published: January 2024

Abstract
Background
The epithelial–mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells participated in the development of retinal fibrosis. SB431542 is a small molecule inhibitor with inhibitory effects on the ALK4, ALK5 and ALK7. Our study aimed to explore the effect of SB431542 on the EMT of RPE cells and to provide new ideas for the treatment of retinal fibrosis.

Methods
We performed fundus fluorescein angiography, optical coherence tomography and hematoxylin–eosin staining in vivo to observe the effect of SB431542 on choroidal neovascularization (CNV)-induced retinopathy. The proliferation, migration, cytoskeleton, adhesion, reactive oxygen species (ROS), mitochondrial morphology and membrane potential of RPE cells were observed in vitro through fluorescein diacetate staining, Cell Counting Kit-8 experiment, wound healing assay, phalloidin staining, immunofluorescence, MitoSOX, DCFH-DA, MitoTracker and JC-10 staining. Western blot, reverse transcription quantitative and immunofluorescence were used to detect the expression of EMT–related markers, pERK1/2, pGSK3β and β-catenin.

Results
SB431542 significantly alleviated retinopathy in the CNV model. The proliferation, migration and adhesion in RPE cells decreased to a certain extent in SB431542 treatment. SB431542 partially normalized the structure of RPE cells. The expression levels of E-cadherin increased, while the expression levels of laminin and N-cadherin decreased with SB431542 treatment. SB431542 reduced the production of total ROS, mitochondrial SOX and recovered the mitochondrial membrane potential to a certain degree. In addition, our study showed that SB431542 downregulated the phosphorylation of ERK1/2, GSK3β and the expression of β-catenin.

Conclusion
SB431542 improved EMT in RPE cells by maintaining mitochondrial homeostasis via the ERK1/2 and GSK3β/β-catenin pathways.

Graphical Abstract
SB431542 inhibits EMT in RPE cells under high glucose conditions.
Translational medicine for acute lung injury
Authors: Zhang Jianguo , Guo Yumeng , Mak Michael , Tao Zhimin 
Published: January 2024

AbstractAcute lung injury (ALI) is a complex disease with numerous causes. This review begins with a discussion of disease development from direct or indirect pulmonary insults, as well as varied pathogenesis. The heterogeneous nature of ALI is then elaborated upon, including its epidemiology, clinical manifestations, potential biomarkers, and genetic contributions. Although no medication is currently approved for this devastating illness, supportive care and pharmacological intervention for ALI treatment are summarized, followed by an assessment of the pathophysiological gap between human ALI and animal models. Lastly, current research progress on advanced nanomedicines for ALI therapeutics in preclinical and clinical settings is reviewed, demonstrating new opportunities towards developing an effective treatment for ALI.
Cervical lymphoepithelioma-like carcinoma with deficient mismatch repair and loss of SMARCA4/BRG1: a case report and five related cases
Authors: Miyama Yu , Kato Tomomi , Sato Masayasu , Yabuno Akira , Hasegawa Kosei , Yasuda Masanori 
Published: January 2024

Abstract
Background
We encountered a cervical lymphoepithelial carcinoma (LEC) possessing a predominantly solid architecture with deficient mismatch repair (dMMR) and loss of expression of the SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex subunit. This is the first case report of LEC with dMMR and loss of SWI/SNF complex subunit.

Case presentation
A 34-year-old woman presented at our hospital with menstrual irregularities and abnormal vaginal bleeding. Magnetic resonance imaging revealed an exophytic mass in the posterior uterine cervix. Biopsy specimens confirmed squamous cell carcinoma with a 2018 International Federation of Gynecology and Obstetrics (FIGO) uterine cervical cancer stage of IB2. In a subsequent conization specimen, the tumor appeared exophytic. Microscopically, the tumor cells formed a predominant solid architecture. Abundant lymphocytic infiltration was observed. The pathological diagnosis indicated human papillomavirus (HPV)-associated squamous cell carcinoma with LEC pattern and pT1b2. Immunohistochemically, high programmed death-ligand 1 (PD-L1) expression, dMMR, and loss of the switch/sucrose non-fermentable family-related, matrix-associated, actin-dependent regulator of chromatin subfamily member 4 (SMARCA4)/BRG1, an SWI/SNF complex subunit, were observed. The patient underwent a radical hysterectomy and is alive without disease one year and five months later. Our analysis of five additional LEC cases revealed a consistent association with high-risk HPV and elevated PD-L1 expression. In addition to the present case, another patient exhibited dMMR. The SWI/SNF complex was retained except in the present case. The prognosis was favorable in all cases.

Conclusions
This unique case of LEC with dMMR suggests a distinct clinical entity with potential immunotherapy implications. Analysis of the other five LEC cases revealed that LEC was immune hot, and immune checkpoint inhibitors may be effective. The two dMMR cases showed loss of MLH1 and PMS2 expressions, and prominently high tumor PD-L1 expression. In those cases, dMMR might have contributed to the morphological characteristics of LEC.
Translation and validation of the Breastfeeding Motivation Scale in China
Authors: Yu Yanfei , Zhang Lu , Liu Ying , Zhang Lan , Guo Nafei 
Published: January 2024

Abstract
Background
There are several versions of the Breastfeeding Motivation Scale (BMS), which have been shown to measure maternal breastfeeding motivation, but there is not a Chinese version yet. The study aimed to translate the BMS into Chinese and subsequently assess its psychometric properties among Chinese mothers during the postpartum period.

Methods
The study was composed of two phases. The translation of BMS closely followed the principals of good practices. Phase 1 included a comprehensive translation, back-translation, cross-cultural adaptation, and pretest to develop the Chinese version of the BMS. From 1 December 2021 to 1 July 2022, the Chinese version of the BMS was administered to 206 postnatal mothers in our maternity wards to assess its psychometric properties. Phase 2 involved psychometric property testing, including testing of the internal consistency, test–retest reliability, content validity, construct validity, convergent validity and discriminant validity.

Results
Minor modifications in four items were recommended after translations. The Cronbach's α coefficient of the Chinese version of the BMS was .887, and the intraclass correlation coefficient was .897 (P < 0.001). The model fit was acceptable (χ2/df = 2.40, P < 0.001, RMSEA = 0.08, CFI = 0.91, IFI = 0.92 and TLI = 0.90) according to the confirmatory factor analysis. The composite reliability values corresponding to each latent variable were 0.733 ~ 0.926, and the average variance extracted values were 0.476 ~ 0.653. The correlations among the five measured variables were all lower than .85 and the square roots of average variance extracted from the variable were greater than the interconstruct correlations among the five measured variables in the model.

Conclusions
The Chinese version of the BMS has good reliability and validity and provides a reliable assessment tool for measuring maternal breastfeeding motivation. It also provides support to develop culturally sensitive interventions for Chinese mothers’ who are breastfeeding.
Comparing the effects of decreasing prescription opioid shipments and the release of an abuse deterrent OxyContin formulation on opioid overdose fatalities in WV: an interrupted time series study
Authors: Lundstrom Eric W. , Dai Zheng , Groth Caroline P. , Hendricks Brian , Winstanley Erin L. , Abate Marie , Smith Gordon S. 
Published: January 2024

Abstract
Introduction
The 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV).

Methods
Opioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006–2014) and the WV Forensic Drug Database (2005–2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC).

Results
The majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date.

Discussion
We found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006–2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.
Evaluation of PTV margins with daily iterative online adaptive radiotherapy for postoperative treatment of endometrial and cervical cancer: a prospective single-arm phase 2 study
Authors: Wang Guangyu , Wang Zhiqun , Guo Yuping , Zhang Yu , Qiu Jie , Hu Ke , Li Jing , Yan JunFang , Zhang Fuquan 
Published: January 2024

Abstract
Background
To determine the optimal planning target volume (PTV) margins for adequate coverage by daily iterative cone-beam computed tomography (iCBCT)-guided online adaptive radiotherapy (oART) in postoperative treatment of endometrial and cervical cancer and the benefit of reducing PTV margins.

Methods
Fifteen postoperative endometrial and cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective phase 2 study. Pre- and posttreatment iCBCT images of 125 fractions from 5 patients were obtained as a training cohort, and clinical target volumes (CTV) were contoured separately. Uniform three-dimensional expansions were applied to the PTVpre to assess the minimum margin required to encompass the CTVpost. The dosimetric advantages of the proposed online adaptive margins were compared with conventional margin plans (7–15 mm) using an oART emulator in another cohort of 125 iCBCT scans. A CTV-to-PTV expansion was verified on a validation cohort of 253 fractions from 10 patients, and further margin reduction and acute toxicity were studied.

Results
The average time from pretreatment iCBCT to posttreatment iCBCT was 22 min. A uniform PTV margin of 5 mm could encompass nodal CTVpost in 100% of the fractions (175/175) and vaginal CTVpost in 98% of the fractions (172/175). The margin of 5 mm was verified in our validation cohort, and the nodal PTV margin could be further reduced to 4 mm if ≥ 95% CTV coverage was predicted to be achieved. The adapted plan with a 5 mm margin significantly improved pelvic organ-at-risk dosimetry compared with the conventional margin plan. Grade 3 toxicities were observed in only one patient with leukopenia, and no patients experienced acute urinary toxicity.

Conclusion
In the postoperative treatment of endometrial and cervical cancer, oART could reduce PTV margins to 5 mm, which significantly decrease the dose to critical organs at risk and potentially lead to a lower incidence of acute toxicity.
Anatomic distribution of basivertebral foramen with a magistral form in vertebral bodies of T10~L5 and its clinical significance for extensive epidural cement leakage in cement-augmented pedicle screw fixation: a multicenter case–control study
Authors: Yu Weibo , Cai Daozhang , Yao Zhensong , Zhang Haiyan , Jiang Xiaobing 
Published: January 2024

Abstract
Background
There are no reports discussing anatomic distribution of basivertebral foramen (BVF) in the osteoporotic vertebral body, which is critical in the analysis of the risk of epidural cement leakage (ECL) after cement-augmented pedicle screw fixation (CAPSF).

Methods
371 osteoporotic patients using 1898 cement-augmented screws were included. Preoperative computed tomography (CT) was used to determine the frequency, width, height, and depth of magistral BVF in T10~L5. Additionally, we measured the distance between BVF and the left/right borders of vertebral body as well as the distance between BVF and upper/lower endplates. Following CAPSF, the severity of ECL and the position of pedicle screws were determined by postoperative CT. Finally, significant risk factors for extensive ECL were identified through binary logistic regression analysis.

Results
Of 2968 vertebral bodies ranging from T10 to L5, 801 (42.2%) had a magistral BVF. From T10 to L5, the frequency of magistral BVF appeared to gradually increase. The magistral BVF was much closer to the upper endplate and the depth accounted for about a quarter of anteroposterior diameter of vertebral body. Overall, there were 19 patients (5.1%) and 32 screws (1.7%) with extensive ECL, nine of whom had neurological symptoms. The independent risk factors for extensive ECL were the magistral BVF (OR = 8.62, P < 0.001), more volume of cement injected (OR = 1.57, P = 0.031), reduced distance from screw tip to vertebral midline (OR = 0.76, P = 0.003) and vertebral posterior wall (OR = 0.77, P < 0.001) respectively.

Conclusion
When planning a CAPSF procedure, it is important to consider anatomical distribution of BVF and improve screw implantation methods.
m6A-modified circARHGAP12 promotes the aerobic glycolysis of doxorubicin-resistance osteosarcoma by targeting c-Myc
Authors: Zhang Dawei , Guo Qingzhu , You Kemin , Zhang Yi , Zheng Yao , Wei Tao 
Published: January 2024

AbstractChemotherapy resistance accompanied by energy metabolism abnormality functions as one of the main reasons for treatment failure and poor prognosis. However, the function of N6-methyladenosine (m6A)-modified circular RNA (circRNA) on osteosarcoma (OS) is still unclear. Here, present research investigated the potential role and mechanism of circARHGAP12 on OS doxorubicin (Dox) resistance and aerobic glycolysis. Results indicated that circARHGAP12 was a novel m6A-modified circRNA, which was up-regulated in OS cells. Overexpression of circARHGAP12 promoted the Dox resistance half-maximal inhibitory concentration (IC50) and aerobic glycolysis (glucose uptake, lactate and ATP production) in OS cells (Saos-2/Dox, MG63/Dox). Mechanistically, m6A-modified circARHGAP12 could bind with c-Myc mRNA through m6A-dependent manner, thereby enhancing the c-Myc mRNA stability. Thus, these findings revealed the critical function of circARHGAP12 on OS Dox-resistance and aerobic glycolysis. Taken together, our study demonstrated a critical function of circARHGAP12 on OS chemotherapy resistance and energy metabolism abnormality, providing critical roles on OS treatment.
Contribution of genetic variants to congenital heart defects in both singleton and twin fetuses: a Chinese cohort study
Authors: Lin Shaobin , Shi Shanshan , Lu Jian , He Zhiming , Li Danlun , Huang Linhuan , Huang Xuan , Zhou Yi , Luo Yanmin 
Published: January 2024

Abstract
Background
The contribution of genetic variants to congenital heart defects (CHDs) has been investigated in many postnatal cohorts but described in few prenatal fetus cohorts. Overall, specific genetic variants especially copy number variants (CNVs) leading to CHDs are somewhat diverse among different prenatal cohort studies. In this study, a total of 1118 fetuses with confirmed CHDs were recruited from three units over a 5-year period, composing 961 of singleton pregnancies and 157 of twin pregnancies. We performed chromosomal microarray analysis on all cases to detect numerical chromosomal abnormalities (NCAs) and pathogenic/likely pathogenic CNVs (P/LP CNVs) and employed whole-exome sequencing for some cases without NCAs and P/LP CNVs to detect P/LP sequence variants (P/LP SVs).

Results
Overall, NCAs and P/LP CNVs were identified in 17.6% (197/1118) of cases, with NCA accounting for 9.1% (102/1118) and P/LP CNV for 8.5% (95/1118). Nonisolated CHDs showed a significantly higher frequency of NCA than isolated CHD (27.3% vs. 4.4%, p < 0.001), but there was no significant difference in the frequency of P/LP CNVs between isolated and nonisolated CHD (11.7% vs. 7.7%). A total of 109 P/LP CNVs were identified in 95 fetuses, consisting of 97 (89.0%) de novo, 6 (5.5%) parental inherited and 6 (5.5%) with unavailable parental information. The 16p11.2 proximal BP4-BP5 deletion was detected in 0.9% (10/1118) of all cases, second only to the most common 22q11.21 proximal A-D deletion (2.1%, 23/1118). Most of the 16p11.2 deletions (8/10) detected were de novo, and were enriched in CHD cases compared with a control cohort from a previous study. Additionally, SV was identified in 12.9% (8/62) of cases without NCA and P/LP CNV, most of which were de novo with autosomal dominant inheritance.

Conclusions
Our cohort study provides a deep profile of the contribution of genetic variants to CHDs in both singleton and twin fetuses; NCA and P/LP CNV contribute to 9.1% and 8.5% of CHD in fetuses, respectively. We confirmed the 16p11.2 deletion as a CHD-associated hotspot CNV, second only to the 22q11.21 deletion in frequency. Most 16p11.2 deletions detected were de novo. Additionally, P/LP SV was identified in 12.9% (8/62) of fetuses without NCA or P/LP CNV.
The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors
Authors: Wei Qing , Li Peijing , Yang Teng , Zhu Jiayu , Sun Lu , Zhang Ziwen , Wang Lu , Tian Xuefei , Chen Jiahui , Hu Can , Xue Junli , Ma Letao , Shimura Takaya , Fang Jianmin , Ying Jieer , Guo Peng , Cheng Xiangdong 
Published: January 2024

AbstractAntibody-drug conjugates (ADCs) represent an important class of cancer therapies that have revolutionized the treatment paradigm of solid tumors. To date, many ongoing studies of ADC combinations with a variety of anticancer drugs, encompassing chemotherapy, molecularly targeted agents, and immunotherapy, are being rigorously conducted in both preclinical studies and clinical trial settings. Nevertheless, combination therapy does not always guarantee a synergistic or additive effect and may entail overlapping toxicity risks. Therefore, understanding the current status and underlying mechanisms of ADC combination therapy is urgently required. This comprehensive review analyzes existing evidence concerning the additive or synergistic effect of ADCs with other classes of oncology medicines. Here, we discuss the biological mechanisms of different ADC combination therapy strategies, provide prominent examples, and assess their benefits and challenges. Finally, we discuss future opportunities for ADC combination therapy in clinical practice.