bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of co-expressed central genes and transcription factors in acute myocardial infarction and diabetic nephropathy
Authors: Li Bo , Zhao Xu , Xie Wanrun , Hong Zhenzhen , Cao Ye , Zhang Yi , Ding Yan 
Published: May 2024

Abstract
Background
Acute myocardial infarction (AMI) and diabetic nephropathy (DN) are common clinical co-morbidities, but they are challenging to manage and have poor prognoses. There is no research on the bioinformatics mechanisms of comorbidity, and this study aims to investigate such mechanisms.

Methods
We downloaded the AMI data (GSE66360) and DN datasets (GSE30528 and GSE30529) from the Gene Expression Omnibus (GEO) platform. The GSE66360 dataset was divided into two parts: the training set and the validation set, and GSE30529 was used as the training set and GSE30528 as the validation set. After identifying the common differentially expressed genes (DEGs) in AMI and DN in the training set, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and protein–protein interaction (PPI) network construction were performed. A sub-network graph was constructed by MCODE, and 15 hub genes were screened by the Cytohubba plugin. The screened hub genes were validated, and the 15 screened hub genes were subjected to GO, KEGG, Gene MANIA analysis, and transcription factor (TF) prediction. Finally, we performed TF differential analysis, enrichment analysis, and TF and gene regulatory network construction.

Results
A total of 46 genes (43 up-regulated and 3 down-regulated) were identified for subsequent analysis. GO functional analysis emphasized the presence of genes mainly in the vesicle membrane and secretory granule membrane involved in antigen processing and presentation, lipopeptide binding, NAD + nucleosidase activity, and Toll-like receptor binding. The KEGG pathways analyzed were mainly in the phagosome, neutrophil extracellular trap formation, natural killer cell-mediated cytotoxicity, apoptosis, Fc gamma R-mediated phagocytosis, and Toll-like receptor signaling pathways. Eight co-expressed hub genes were identified and validated, namely TLR2, FCER1G, CD163, CTSS, CLEC4A, IGSF6, NCF2, and MS4A6A. Three transcription factors were identified and validated in AMI, namely NFKB1, HIF1A, and SPI1.

Conclusions
Our study reveals the common pathogenesis of AMI and DN. These common pathways and hub genes may provide new ideas for further mechanistic studies.
Combination of betulinic acid and EGFR-TKIs exerts synergistic anti-tumor effects against wild-type EGFR NSCLC by inducing autophagy-related cell death via EGFR signaling pathway
Authors: Wang Han , Du Xiaohui , Liu Wenwen , Zhang Congcong , Li Ying , Hou Jingwen , Yu Yi , Li Guiru , Wang Qi 
Published: May 2024

Abstract
Background
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung cancer patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type EGFR tumors has been shown to be marginal. Methods that can sensitize EGFR-TKIs to EGFR wild-type NSCLC remain rare. Hence, we determined whether combination treatment can maximize the therapeutic efficacy of EGFR-TKIs.

Methods
We established a focused drug screening system to investigate candidates for overcoming the intrinsic resistance of wild-type EGFR NSCLC to EGFR-TKIs. Molecular docking assays and western blotting were used to identify the binding mode and blocking effect of the candidate compounds. Proliferation assays, analyses of drug interactions, colony formation assays, flow cytometry and nude mice xenograft models were used to determine the effects and investigate the molecular mechanism of the combination treatment.

Results
Betulinic acid (BA) is effective at targeting EGFR and synergizes with EGFR-TKIs (gefitinib and osimertinib) preferentially against wild-type EGFR. BA showed inhibitory activity due to its interaction with the ATP-binding pocket of EGFR and dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis. Mechanistic studies revealed that the combination strategy activated EGFR-induced autophagic cell death and that the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell cycle arrest. Activation of the mTOR pathway or blockade of autophagy by specific chemical agents markedly attenuated the effect of cell cycle arrest. In vivo administration of the combination treatment caused marked tumor regression in the A549 xenografts.

Conclusions
BA is a potential wild-type EGFR inhibitor that plays a critical role in sensitizing EGFR-TKI activity. BA combined with an EGFR-TKI effectively suppressed the proliferation and survival of intrinsically resistant lung cancer cells via the inhibition of EGFR as well as the induction of autophagy-related cell death, indicating that BA combined with an EGFR-TKI may be a potential therapeutic strategy for overcoming the primary resistance of wild-type EGFR-positive lung cancers.

Graphical abstract
Lipid-based insulin-resistance markers predict cardiovascular events in metabolic dysfunction associated steatotic liver disease
Authors: Colantoni Alessandra , Bucci Tommaso , Cocomello Nicholas , Angelico Francesco , Ettorre Evaristo , Pastori Daniele , Lip Gregory Y.H. , Del Ben Maria , Baratta Francesco 
Published: May 2024

Abstract
Background
Insulin resistance (IR) is the cornerstone of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), pathophysiologically being the key link between MASLD, metabolic disorders, and cardiovascular (CV) diseases. There are no prospective studies comparing the predictive values of different markers of insulin resistance (IR) in identifying the presence of MASLD and the associated risk of cardiovascular events (CVEs).

Methods
Post hoc analysis of the prospective Plinio Study, involving dysmetabolic patients evaluated for the presence of MASLD. The IR markers considered were Homeostatic Model Assessment for IR (HOMA-IR), Triglycerides-Glycemia (TyG) index, Triglycerides to High-Density Lipoprotein Cholesterol ratio (TG/HDL-C), Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI). Receiver operative characteristic (ROC) analyses were performed to find the optimal cut-offs of each IR marker for detecting MASLD and predicting CVEs in MASLD patients. Logistic and Cox multivariable regression analyses were performed, after dichotomizing the IR markers based on the optimal cut-offs, to assess the factors independently associated with MASLD and the risk of CVEs.

Results
The study included 772 patients (age 55.6 ± 12.1 years, 39.4% women), of whom 82.8% had MASLD. VAI (Area Under the Curve [AUC] 0.731), TyG Index (AUC 0.723), and TG/HDL-C ratio (AUC: 0.721) predicted MASLD but was greater with HOMA-IR (AUC: 0.792) and LAP (AUC: 0.787). After a median follow-up of 48.7 (25.4–75.8) months, 53 MASLD patients experienced CVEs (1.8%/year). TyG index (AUC: 0.630), LAP (AUC: 0.626), TG/HDL-C (AUC: 0.614), and VAI (AUC: 0.590) demonstrated comparable, modest predictive values in assessing the CVEs risk in MASLD patients.

Conclusion
In dysmetabolic patients HOMA-IR and LAP showed the best accuracy in detecting MASLD. The possible use of lipid-based IR markers in stratifying the CV risk in patients with MASLD needs further validation in larger cohorts.
A new insight on evaluation of the fertility and pregnancy outcome in patients with primary Sjögren syndrome: a propensity score matched study in multi-IVF centers
Authors: Mao Ruolin , Zhu Lixia , Long Rui , Zhou Juepu , Wang Xiangfei , Wang Meng , Wang Tiantian , Li Youzhu , Long Hui , Jin Lei 
Published: May 2024

Abstract
Background
Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it’s currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it’s unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients.

Objective
This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers.

Methods
We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching.

Results
Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison.

Conclusion
Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.
In vitro fertilization outcome based on the detailed early luteal phase trajectory of hormones: a prospective cohort study
Authors: N Vuong Lan , D Pham Toan , N A Ho Vu , T L Vu Anh , M Ho Tuong , Yding Andersen Claus 
Published: May 2024

Abstract
Background
Ovarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer.

Methods
This prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18–38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile.

Results
Ninety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28–3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03–4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth.

Conclusions
These data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF.

Trial Registration
NCT04693624 (www.clinicaltrials.gov).
The use of accelerometer bracelets to evaluate arm motor function over a stroke rehabilitation period – an explorative observational study
Authors: Lyckegård Finn Eric , Carlsson Håkan , Ericson Petter , Åström Kalle , Brogårdh Christina , Wasselius Johan 
Published: May 2024

Abstract
Background
Assessments of arm motor function are usually based on clinical examinations or self-reported rating scales. Wrist-worn accelerometers can be a good complement to measure movement patterns after stroke. Currently there is limited knowledge of how accelerometry correlate to clinically used scales. The purpose of this study was therefore to evaluate the relationship between intermittent measurements of wrist-worn accelerometers and the patient’s progression of arm motor function assessed by routine clinical outcome measures during a rehabilitation period.

Methods
Patients enrolled in in-hospital rehabilitation following a stroke were invited. Included patients were asked to wear wrist accelerometers for 24 h at the start (T1) and end (T2) of their rehabilitation period. On both occasions arm motor function was assessed by the modified Motor Assessment Scale (M_MAS) and the Motor Activity Log (MAL). The recorded accelerometry was compared to M_MAS and MAL.

Results
20 patients were included, of which 18 completed all measurements and were therefore included in the final analysis. The resulting Spearman’s rank correlation coefficient showed a strong positive correlation between measured wrist acceleration in the affected arm and M-MAS and MAL values at T1, 0.94 (p < 0.05) for M_MAS and 0.74 (p < 0.05) for the MAL values, and a slightly weaker positive correlation at T2, 0.57 (p < 0.05) for M_MAS and 0.46 − 0.45 (p = 0.06) for the MAL values. However, no correlation was seen for the difference between the two sessions.

Conclusions
The results confirm that the wrist acceleration can differentiate between the affected and non-affected arm, and that there is a positive correlation between accelerometry and clinical measures. Many of the patients did not change their M-MAS or MAL scores during the rehabilitation period, which may explain why no correlation was seen for the difference between measurements during the rehabilitation period. Further studies should include continuous accelerometry throughout the rehabilitation period to reduce the impact of day-to-day variability.
Clinical differences between periprosthetic and native distal femur fractures: a comparative observational study
Authors: Kong Shana , Tse Shannon , Saade Aziz , Bautista Barry , Haffner Max , Saiz Augustine M. 
Published: May 2024

Abstract
Introduction
The incidence of periprosthetic distal femur fractures (PDFF) is increasing as the number of total knee replacements becomes more common. This study compared the demographics, fracture characteristics, treatment, and outcomes of periprosthetic versus native distal femur fractures (NDFF).

Materials and methods
This was a retrospective cohort study of patients ≥ 18 who underwent surgical fixation of NDFF or PDFF from 2012 to 2020 at a level-1 trauma center. The main variables collected included demographics, AO/OTA fracture classification, fixation construct, concomitant fractures, polytrauma rates, bone density, and reduction quality. Primary outcomes were unexpected return to the operating room (UROR), hospital length of stay, and quality of reduction. T-tests, Fisher’s exact tests, and multivariate analyses were used for statistical analysis.

Results
209 patients were identified, including 70 PDFF and 139 NDFF. PDFF patients were elderly females (81%) with isolated (80%) and comminuted (85%) 33 A.3 (71%) fractures. NDFF patients included 53% females, were commonly middle-aged, and displayed comminuted (92%) 33 C.2 fractures. 48% of NDFF patients had concomitant fractures. Intramedullary nailing was the primary fixation for both groups, followed by nail-plate combination (37%) for PDFF and lateral locking plates (21%) for NDFF. NDFF patients experienced significantly longer hospital stays, higher UROR rates, and worse quality of reduction (p < 0.05). PDFF patients had a significantly greater prevalence of low bone density (p < 0.05).

Conclusion
PDFF occur as isolated injuries with significant metaphyseal comminution in elderly females with low bone quality. NDFF commonly occurs in younger patients with less metaphyseal comminution and concomitant fractures. Intramedullary nailing was the most common treatment for both groups, although preference for nail-plate combination fixation is increasing. NDFF type 33 C fractures are at greater risk of UROR.
Bacteriophage-derived endolysins as innovative antimicrobials against bovine mastitis-causing streptococci and staphylococci: a state-of-the-art review
Authors: Vander Elst Niels 
Published: May 2024

AbstractBacteriophage-encoded endolysins, peptidoglycan hydrolases breaking down the Gram-positive bacterial cell wall, represent a groundbreaking class of novel antimicrobials to revolutionize the veterinary medicine field. Wild-type endolysins exhibit a modular structure, consisting of enzymatically active and cell wall-binding domains, that enable genetic engineering strategies for the creation of chimeric fusion proteins or so-called ‘engineered endolysins’. This biotechnological approach has yielded variants with modified lytic spectrums, introducing new possibilities in antimicrobial development. However, the discovery of highly similar endolysins by different groups has occasionally resulted in the assignment of different names that complicate a straightforward comparison. The aim of this review was to perform a homology-based comparison of the wild-type and engineered endolysins that have been characterized in the context of bovine mastitis-causing streptococci and staphylococci, grouping homologous endolysins with ≥ 95.0% protein sequence similarity. Literature is explored by homologous groups for the wild-type endolysins, followed by a chronological examination of engineered endolysins according to their year of publication. This review concludes that the wild-type endolysins encountered persistent challenges in raw milk and in vivo settings, causing a notable shift in the field towards the engineering of endolysins. Lead candidates that display robust lytic activity are nowadays selected from screening assays that are performed under these challenging conditions, often utilizing advanced high-throughput protein engineering methods. Overall, these recent advancements suggest that endolysins will integrate into the antibiotic arsenal over the next decade, thereby innovating antimicrobial treatment against bovine mastitis-causing streptococci and staphylococci.
PD-1 blockade immunotherapy as a successful rescue treatment for disseminated adenovirus infection after allogeneic hematopoietic stem cell transplantation
Authors: Zhou Fei , Du Feng , Wang Ziyan , Xue Mengxing , Wu Depei , Chen Suning , He Xuefeng 
Published: May 2024

AbstractDisseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection in the early posttransplant period. The patient was diagnosed with diffuse large B-cell lymphoma at first and underwent 8 cycles of chemotherapy, including rituximab. She was subsequently diagnosed with acute myeloid leukemia and received haploidentical transplantation. She was diagnosed with Epstein‒Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) 2 months after the transplant, and 3 doses of rituximab were administered. The patient was diagnosed with disseminated adenovirus infection with upper respiratory tract, gastrointestinal tract and blood involved at 3 months after transplantation. She was first treated with a reduction in immunosuppression, cidofovir and ribavirin. Then, the patient received salvage treatment with the PD-1 inhibitor sintilimab (200 mg) after achieving no response to conventional therapy. The adenovirus was cleared 3 weeks later, and concomitant EBV was also cleared. Although the patient developed graft-versus-host disease of the liver after the administration of the PD-1 inhibitor, she was cured with steroid-free therapy. Therefore, PD-1 blockade immunotherapy can be considered a promising treatment option for patients with disseminated adenovirus infection after transplantation, with fully weighing the hazards of infection and the side effects of this therapy.
Impact of COVID-19 pandemic on prescription of psychotropic medications in the Italian paediatric population during 2020
Authors: Gallinella Francesca , Trotta Francesco , Fortinguerra Filomena 
Published: May 2024

Abstract
Background
There is a global perception that psychotropic utilization in children and adolescents is increasing, especially with the onset of COVID-19 pandemic. Available literature data on paediatric psychotropic medication prescriptions in Italy are limited to one or few regions and not updated. The aim of this study was to provide updated data on psychotropic prescriptions referred to the whole Italian paediatric population, as overall and by subgroups of medications and to evaluate if the COVID-19 pandemic during 2020 had an impact on prescription rates.

Methods
A descriptive study on psychotropic drug utilization in children and adolescents (< 18 years) resident in all Italian regions during 2020 was performed. Patients registered in the Pharmaceutical Prescriptions database with at least one prescription/dispensing of a psychotropic medication (antipsychotics-N05A), (antidepressants-N06A) and (psychostimulants-N06BA) during the study period were considered. The indicators used were the prescription rate (number of prescriptions per 1000 children) and prevalence of use (proportion of the paediatric population with at least one prescription in the relevant year).

Results
During the 2020 the prevalence of psychotropic drug use in the paediatric population was 0.3%, increased of 7.8% if compared to 2019. The same trend was observed for the prescription rate, which recorded an average of 28.2 per 1000 children with an increase of 11.6% if compared to previous year, representing the 0.6% of the overall drug use in this age group. The data showed a growing trend prescription by age, reaching the peak in adolescents aged 12–17 years old, with a prescription rate of 65 per 1000 children and a prevalence of 0.71%. Considering the subgroups of psychotropic medications, the highest prevalence of use was found for antipsychotic drugs, received by the 0.19% of the paediatric population during 2020.

Conclusions
Psychotropic drug utilization in children and adolescents has grown during 2020 in Italy and worldwide, raising alarms from health care clinicians and patient advocates about the increase of burden of mental diseases in paediatric population during the COVID-19 pandemic. A more systematic monitoring of the use of psychotropic medications should be implemented in all countries for collecting relevant information about children and adolescents taking psychotropic drugs, in order to address the present and the future of the mental health of the paediatric population.