bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early monitoring of anti-infliximab antibodies by drug-tolerant assay predicts later immunogenicity and drug survival in rheumatic diseases
Authors: Martínez-Feito Ana , Novella-Navarro Marta , Hernández-Breijo Borja , Nozal Pilar , Peiteado Diana , Villalba Alejandro , Nuño Laura , Monjo Irene , Pascual-Salcedo Dora , Balsa Alejandro , Plasencia-Rodríguez Chamaida 
Published: January 2024

Abstract

Objectives
To investigate the appearance of anti-drug antibodies (ADA) against infliximab (IFX) determined by drug-sensitive and drug-tolerant assays and their relationship with drug levels and drug survival.

Methods
This longitudinal observational study included 45 patients with RA and 61 with SpA. Serum samples were obtained at weeks 2, 6, 12, 24 and 52. Serum IFX levels were measured by a capture ELISA and ADA by an in-house drug-sensitive two-site (bridging) ELISA (bELISA) and a commercially available drug-tolerant ELISA (IDK, Immundiagnostik, Germany).

Results
ADA were detected earlier by IDK than by bELISA. Once ADA appeared, positivity persisted throughout the study period. Patients who were bELISA ADA+ had higher IDK ADA levels (than bELISA ADA– patients). Circulating IFX levels were detected in all patients except those found to be bELISA ADA+. Serum IFX levels were lower in IDK ADA+ than in IDK ADA– patients. Most patients (64%) discontinued due to inefficacy. The early onset of immunogenicity was related to IFX survival. In both RA and SpA, the median survival (years) was shorter in patients with earlier development of ADA (IDK+ before or at week 24) than those who became IDK+ later (after week 24) or never developed ADA.

Conclusion
A drug-tolerant assay detects ADA during IFX therapy earlier and more frequently than a drug-sensitive assay. The onset of immunogenicity detected by drug-tolerant assays is related to the subsequent detection of ADA by drug-sensitive assays and drug survival.
Comparative Analysis of the Avirulence Effectors Produced by the Fungal Stem Rust Pathogen of Wheat
Authors: Lubega Jibril , Figueroa Melania , Dodds Peter N. , Kanyuka Kostya 
Published: January 2024

Crops are constantly exposed to pathogenic microbes. Rust fungi are examples of these harmful microorganisms, which have a major economic impact on wheat production. To protect themselves from pathogens like rust fungi, plants employ a multilayered immune system that includes immunoreceptors encoded by resistance genes. Significant efforts have led to the isolation of numerous resistance genes against rust fungi in cereals, especially in wheat. However, the evolution of virulence of rust fungi hinders the durability of resistance genes as a strategy for crop protection. Rust fungi, like other biotrophic pathogens, secrete an arsenal of effectors to facilitate infection, and these are the molecules that plant immunoreceptors target for pathogen recognition and mounting defense responses. When recognized, these effector proteins are referred to as avirulence (Avr) effectors. Despite the many predicted effectors in wheat rust fungi, only five Avr genes have been identified, all from wheat stem rust. Knowledge of the Avr genes and their variation in the fungal population will inform deployment of the most appropriate wheat disease-resistance genes for breeding and farming. The review provides an overview of methodologies as well as the validation techniques that have been used to characterize Avr effectors from wheat stem rust. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Identification and validation of genes associated with aging‐related cardiovascular disease
Authors: Li Jing , Jiang Shengping , Huang Chengyun , Lu Baihui , Yang Xiaolong 
Published: January 2024

AbstractAging is acknowledged as the most significant risk factor for cardiovascular disease (CVD). This study sought to identify and validate potential aging‐related genes associated with CVD by using bioinformatics. The confluence of the limma test, weighted correlation network analysis (WGCNA), and 2129 aging and senescence‐associated genes led to the identification of aging‐related differential expression genes (ARDEGs). By using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), potential biological roles and pathways of ARDEGs were identified. To find the significantly different functions between CVD and non‐cardiovascular disease (nCVD) and to reckon the processes score, enrichment analysis of all genes was carried out using gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). By using GO and KEGG, potential biological roles and pathways of ARDEGs were identified. To evaluate the immune cell composition of the immune microenvironment, we performed an immune infiltration analysis on the dataset from the training group. We were able to acquire four ARDEGs (PTGS2, MMP9, HBEGF, and FN1). Aging, cellular senescence, and nitric oxide signal transduction were selected for biological function analysis. The diagnostic value of the four ARDEGs in distinguishing CVD from nCVD samples was deemed to be favorable. This research identified four ARDEGs that are associated with CVD. This study provides insight into prospective novel biomarkers for aging‐related CVD diagnosis and progression monitoring.
MiR-335 Improves Functional Recovery in Rats After Spinal Cord Injury and Protects PC12 Cells Against Injury Via the SPI-Bax/Caspase-3 Axis
Authors: Li Zhe , Rong Yanlong , Zhang Yuanshi 
Published: January 2024

Study Design
Animal and cellular models of spinal cord injury (SCI) were used to explore the role of miR-335 in regulating cell viability and apoptosis.

Objective.
To investigate the role and the target of miR-335 in SCI.

Summary of Background.
Based on analysis of the GSE19890 data set, miR-335 was identified as a downregulated microRNA (miRNAs) following SCI. Thus, this study investigated whether downregulation of miR-335 is important in the pathological process of SCI.

Materials and Methods.
The GSE19890 data set investigating the expression profiles of miRNAs after SCI was downloaded from the GEO database. GSE45006 and GSE4550 data sets were used to identify differentially expressed genes between normal samples and SCI samples. The targets of rno-miR-335 were predicted using the TargetScan database.
An experimental model of SCI was established, and agomir-miR-335 was intrathecally injected into rats with SCI. Functional recovery was evaluated by assessment of Basso-Beattie-Bresnahan scores and spinal cord water content and performing hematoxylin-eosin staining. Apoptosis was estimated by TUNEL staining. The H2O2-treated PC12 cells were used as in vitro models of SCI. Cell viability and apoptosis were examined by cell counting kit-8 and flow cytometry. Caspase-3 expression was evaluated by immunofluorescence staining. Levels of miRNAs and mRNAs were measured by reverse transcriptase quantitative polymerase chain reaction. Western blotting was performed to measure Bcl-2, Bax, cleaved caspase-3, and specificity protein 1 (SP1) protein levels.

Results.
For in vivo studies, miR-335 was downregulated following SCI, and agomir-miR-335 delivery improved functional recovery through suppressing neuronal apoptosis by inactivating the SP1-Bax/Bcl-2/caspase-3 signaling. During in vitro analysis, miR-335 protected PC12 cells against H2O2-induced damage by negatively regulating the SP1-Bax/Bcl-2/caspase-3 signaling axis. Moreover, upregulation of SP1 abolished the apoptosis suppressive effects of miR-335 upregulation.

Conclusion.
MiR-335 ameliorates locomotor impairment in rats with SCI through the suppression of neuronal apoptosis by inactivating SP1-Bax/Bcl-2/caspase-3 signaling.
External Validation of the Spinal Orthopedic Research Group Index for Spinal Epidural Abscess 90-Day Mortality in a Geographically Remote Population
Authors: Petrie Liam , Boukebous Baptiste , Baker Joseph F. 
Published: January 2024

Study Design.
Retrospective cohort study.

Objective.
To externally validate the Spinal Orthopaedic Research Group (SORG) index for predicting 90-day mortality from spinal epidural abscess and compare its utility to the 11-item modified frailty index (mFI-11) and Charlson comorbidity index (CCI).

Summary of Background Data.
Providing a mortality estimate may guide informed patient and clinician decision-making. A number of prognostic tools and calculators are available to help predict the risk of mortality from spinal epidural abscess, including the SORG index, which estimates 90-day postdischarge mortality. External validation is essential before wider use of any clinical prediction tool.

Materials and Methods.
Patients were identified using hospital coding. Medical and radiologic records were used to confirm the diagnosis. Mortality data and data to calculate the SORG index, mFI-11, and CCI were collected. Area under the curve and calibration plots were used to analyze.

Results.
One hundred and fifty patients were included: 58 were female (39%), with a median age of 63 years. Fifteen deaths (10%) at 90 days postdischarge and 20 (13%) at one year. The mean SORG index was 13.6%, the mean CCI 2.75, and the mean mFI-11 was 1.34. The SORG index (P=0.0006) and mFI-11 (P<0.0001) were associated with 90-day mortality. Area under the curve for SORG, mFI-11, and CCI were 0.81, 0.84, and 0.49, respectively. The calibration slope for the SORG index showed slight overestimation in the middle ranges of the predicted probability, more so than mFI-11, and was not well-calibrated over the higher ranges of predicted probability.

Conclusions.
This study externally validated the SORG index, demonstrating its utility in our population at predicting 90-day mortality; however, it was less well calibrated than the mFI-11. Variations in algorithm performance may be a result of differences in socioethnic composition and health resources between development and validation centres. Continued multicenter data input may help improve such algorithms and their generalisability.
Age at ART initiation and proviral reservoir size in perinatal HIV-1 infection: considerations for ART-free remission
Authors: Bekka Soumia , Kelly Kristen , Haaren Mareike , Dhummakupt Adit , Persaud Deborah 
Published: January 2024

Purpose of review
Achieving ART-free remission without the need for lifelong antiretroviral treatment (ART) is a new objective in HIV-1 therapeutics. This review comprehensively examines the literature to evaluate whether the age at ART initiation in children with perinatal HIV-1 influences the size and decay of the HIV-1 reservoir. The insights gathered from this review serve to inform the field on the unique dynamics of HIV-1 reservoir size in perinatal HIV-1 infection as a function of age at ART initiation, as well as inform biomarker profiling and timing of ART-free remission strategies for children living with HIV-1 globally.

Recent findings
Recent studies demonstrate that initiating very early effective ART in neonates is feasible and limits HIV-1 reservoir size. The clinical relevance of limiting the HIV-1 reservoir size in perinatal infection was recently demonstrated in the Tatelo Study, which investigated a treatment switch from ART to two broadly neutralizing antibodies (bNAbs) in very early treated children. Low proviral reservoir size was associated with sustained virologic control for 24 weeks on bNAbs.

Summary
Immediate and early ART initiation for neonates and infants with perinatal HIV-1 is essential to restricting HIV-1 reservoir size that may enable ART-free remission.
Updates in the treatment of HR+HER2- breast cancer
Authors: Baclig Nikita V. , McCann Kelly E. 
Published: January 2024

Purpose of review
Breast cancer (BC) is the most common cancer among women in the United States and the second leading cause of cancer death. BC research, diagnostics, drug development, and expansion of therapies for novel indications advances so rapidly that BC treatment standards change month-by-month. Herein we discuss notable advancements in the past year for hormone receptor positive (HR+) HER2 negative (HER2−) BC.

Recent findings
Radiolabeled estradiol imaging and circulating tumor DNA (ctDNA) have changed our approach to metastatic BC (mBC) detection. Amongst an abundance of therapy options, treatment de-escalation to avoid toxicities is a priority. Promising results with CDK4/6 inhibitors in the curative setting have been demonstrated even as we await final data for use in the metastatic setting. Several novel endocrine therapies are expected to gain FDA-approval in the near future. Antibody-drug conjugates have expanded from other mBC types to HR+HER2- mBC. The PROMISE trial helped define disease recurrence outcomes for premenopausal women seeking pregnancy.

Summary
The diagnostic and treatment landscape for HR+HER2- BC continues to rapidly evolve on multiple fronts.
Maintenance therapy for newly and recurrent epithelial ovarian cancer: current therapies and future perspectives
Authors: Salutari Vanda , Giudice Elena , Lorusso Domenica 
Published: January 2024

Purpose of review
Epithelial ovarian cancer (EOC) is the fifth cause of cancer death among women, and 70–80% of patients relapse within 2 years from the last cycle of first-line chemotherapy despite a complete response to chemotherapy and optimal debulking surgery. In this context, the goal of the maintenance treatment strategy is to prolong the time to recurrence. The recent development of targeted molecular therapies resulted in a broader spectrum of maintenance therapeutic options with consequent higher clinical benefit but less toxicity. This review summarizes the currently available maintenance strategies for newly and recurrent EOC, focusing on the decision-making process to personalize treatment and future perspectives.

Recent findings
Over the past 10 years, several studies have demonstrated the clear benefit in terms of survival with the addition of a maintenance treatment strategy over the ‘watchful waiting’ approach both in the first line and recurrent setting. Since December 2016, the United States Food and Drug Administration and European Medicines Agency have approved four drugs for ovarian cancer maintenance based on the results of several clinical trials demonstrating efficacy and tolerability. These include the antiangiogenic drug Bevacizumab and three polyadenosine diphosphate-ribose polymerase (PARP) inhibitors: olaparib, niraparib, and rucaparib.

Summary
These data led American and European Treatment guidelines to include bevacizumab, olaparib, niraparib, rucaparib, and combination bevacizumab-olaparib as maintenance treatment options in first-line and recurrent ovarian cancer therapy. However, with the availability of different maintenance options, identifying the best treatment choice for each patient can be challenging, and several clinical and molecular aspects have to be taken into account in the decision-making process.
Retroperitoneal cecal volvulus: a complication of a rare internal hernia – a case report
Authors: Kamaleddine Imad , Popova Magdalena , Angles Theresa , Neese Manuela , Brinkmann Beate , Volmer Erik , Weber Marc-André , Lamprecht Georg , Schafmayer Clemens , Alwali Ahmed 
Published: January 2024

Introduction and importance:
The foramen of Winslow hernia (FWH) is a rare type of internal hernia. In one-third of cases, the cecum was found in the lesser sac. More rarely, the herniated cecum might be volvulated, which represents 1–1.5% of the causes of intestinal obstruction. Once diagnosed, surgical reduction and/or resection of the nonviable herniated bowel is crucial for a positive outcome.

Case presentation:
The authors report a case of retroperitoneal cecal volvulus that complicated FWH in a patient with a history of laparoscopic cholecystectomy.

Clinical discussion:
A delay in the diagnosis is associated with high morbidity and even higher mortality. Because of lacking a consensus, the treatment of FWH depends on the team’s surgical experience.

Conclusion:
Reporting this case will help us to keep in mind this differential diagnosis while treating patients in our daily practice.
Effects of fish oil on ethanol-induced gastric ulcer in rats: inflammatory responses and oxidative stress
Authors: Taheri Mirghaed Mahtab , Ghasemian Seyedeh Ommolbanin , Mousavi Nasab Seyyed Fazlollah , Rahimi Kaveh 
Published: January 2024

Background:
The prevalence of peptic ulcers is increasing due to lifestyle changes and harmful diets.

Objective:
The aim of this study was to investigate the effect of fish oil (FO) on gastric ulcers induced by ethanol in rats.

Methods:
The pharmacological efficacy of FO with doses of 5 and 10 mg/kg investigated using the gastric ulcer index, the acidity of gastric secretions, pro-inflammatory cytokine assessment, and oxidative stress examination.

Results:
Ethanol-induced gastric ulcer improves with FO 5 or 10 mg/kg pretreatment (P<0.05). FO did have acid-neutralizing activity. FO also increased the levels of glutathione and catalase and decreased the malondialdehyde levels (P<0.05). Moreover, FO reduced the levels of tumour necrosis factor alpha (TNF-α) interleukin-6 (IL-6), through downregulation of nuclear factor kappa B (NF-κB) (P<0.05). Pretreatment with FO attenuates ethanol-induced gastric ulceration.

Conclusion:
The observed effects may be due to the role of FO in regulating gastric secretions, changes in the expression of NF-κB, and changes in the levels of oxidative stress factors.
An unusual uterine papillary serous carcinoma with post therapy disseminating metastasis presenting as primary renal malignancy: a case report
Authors: Liu Kuang-Ting , Chang Yueh-Ching , Lin Yu-Chieh , Chang Junn-Liang 
Published: January 2024

Introduction:
Uterine papillary serous carcinoma (UPSC) is a highly aggressive endometrial carcinoma that often presents as a high-stage disease. UPSC has a high propensity for metastasis and recurrence, even with little or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, or peritoneum. However, renal metastasis of UPSC is extremely rare.

Case presentation:
The authors reported a unique UPSC case in a 75-year-old unmarried woman. Twenty years ago, she had a history of right breast cancer and underwent a modified radical mastectomy. Three years ago, she was diagnosed with endometrial carcinoma, and six courses of chemotherapy and radiotherapy were administered. Computed tomography and retrograde pyelography revealed a right renal pelvic tumor, and a right nephroureterectomy was performed. Renal metastatic UPSC was diagnosed. The patient was administered adjuvant chemotherapy.

Clinical discussion:
Metastatic UPSCs initially presenting at distant sites are uncommon manifestations. This tumor should be differentially diagnosed in patients presenting with metastatic high-grade serous papillary carcinoma of unknown primary origin.

Conclusion:
Diagnosing metastatic renal UPSC, based on preoperative and imaging examinations, is often challenging. Thus, a review of the past history, histopathology, and immunohistochemical evaluation plays a crucial and valuable role in the definite and differential diagnosis of this tumor type.
Identification of multiomics map and key biomarkers in uveal melanoma with chromosome 3 loss
Authors: Yong Xi , Kang Tengyao , Li Tingting , Li Sixuan , Hu Xuerui , Yan Xiang , Zhang Fuzhao , Zheng Jianghua , Yang Qin 
Published: January 2024

Purpose:
Chromosome 3 loss is an independent risk factor for uveal melanoma (UM), but its exact molecular mechanisms remain unclear. This study was designed to investigate the relationship between chromosome 3 loss and molecular alterations at multiple levels to construct a prognostic model.

Methods:
Forty-four UM cases with chromosome 3 loss (chr3 del group) and 36 UM cases without copy number variation on chromosome 3 (chr3 wt group) were collected from the Cancer Genome Atlas (TCGA). The TCGA dataset was subjected to a univariate Cox regression analysis to identify different expressed genes, and a subsequent random forest algorithm analysis revealed significant changes in different expressed genes, which were used to develop key biomarkers for UM. Following that, the immune cell infiltration analysis and drug sensitivity analyses were carried out. The UM cell line was then utilized to investigate the potential functions of the key biomarker via cell apoptosis, proliferation, cycle assays, WB, and RT-qPCR.

Results:
By analyzing the 80 cases data in TCGA, the authors unveiled molecular changes relevant to loss of chromosome 3 in UM as well as their poor survival. In addition, machine learning analysis identified three hub genes (GRIN2A, ACAN, and MMP9) as potential therapeutic targets. The differentially enriched pathways between the two groups were mainly about immune-system activity, and hub genes expression was also highly correlated with immune infiltration levels.

Conclusion:
Chromosome 3 loss has considerable clinical significance for UM, and GRIN2A may be useful in diagnosing, treating, and prognosticating the condition.
Capabilities of perinatal healthcare institutions in primary and tertiary care of low birth weight infants in the Federation of Bosnia and Herzegovina: a cross-sectional multicentric study
Authors: Cerovac Anis , Nevačinović Enida , Habek Dubravko , Laganà Antonio Simone , Chiantera Vito , Naem Antoine , Čehić Ermin , Halilović Ramiz , Cerovac Elmedina , Zulović Tarik 
Published: January 2024

Introduction:
Providing adequate healthcare for premature infants is an important issue in perinatal medicine. The aim of this study is to assess the level of the perinatal healthcare institution (PHI) where the newborns were delivered and the possibilities of transporting them to the cantons of the Federation of Bosnia and Herzegovina. The authors also aimed to examine the overall survival of low birth-weight infants (LBWI) in the Federation of Bosnia and Herzegovina and to compare the survival of newborns according to the PHI where they were born and the PHI where they were treated.

Materials and methods:
This cross-sectional study included newborns of both sexes that were born in the maternity wards in 10 cantons of the Federation of Bosnia and Herzegovina with a gestational age between 22 and 42 weeks, and a birth weight less than 2500 g.

Result:
From the PHI of the first and second level, 159 newborns were referred to the third level. A total of 159/669 (23.7%) were referred from a second level PHI to a third level PHI, and 127/669 (l8.9%) LBWI were definitely taken care of. A total of 513/669 (76.8%) LBWI were definitely taken care of in the third level PHI. Out of a total of 159 LBWI referred from other PHI, only 31 (19.5%) LBWI were transported in less than 4 h, and 128 (80.5%) newborns were admitted to the third level PHI within 4 h of birth (P<0.0001). In second level PHI, most LBWI died in the first 12 h after birth, while in third level PHI, 69.2% of LBWI died after 1 week of life.

Conclusion:
Based on world experience and assessment of the situation in Federation of Bosnia and Herzegovina, it is necessary to take measures to improve perinatal care and its regional organization.