bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spine MRI Identifies Clinically Relevant Findings in Patients With Cancer Presenting With Back Pain
Authors: Tringale Kathryn R. , Gangai Natalie , Chua Andrew , Godwin Kendra , Guman Gloria , Laufer Ilya , Cathcart Kathleen N.S. , Lis Eric , Schmitt Adam , Moskowitz Chaya S. , Chilov Marina , Vachha Behroze A. 
Published: August 2023

Study Design.
This is a retrospective, cross-sectional study.

Objective.
The primary aim was to identify the diagnostic yield of spine magnetic resonance imaging (MRI) in detecting malignant pathology in cancer patients with back pain. We also sought to evaluate the role of MRI extent (i.e. regional vs. total) in identifying malignant pathology.

Summary of Background Data.
No prior study has systematically investigated the yield of spine MRI in a large cohort of cancer patients.

Methods.
Spine MRI reports from 2017 to 2021 for back pain (acute and nonspecified chronicity) in cancer patients were reviewed to identify clinically relevant findings: malignant (1) epidural, (2) leptomeningeal, (3) intramedullary, (4) osseous disease, and (5) fracture. Logistic regression was used to evaluate the association between MRI extent and the presence of cancer-related findings. For patients with multiple MRIs, short-interval scans (≤4 mo) were evaluated to assess the yield of repeat imaging.

Results.
At least one cancer-related finding was identified on 52% of 5989 spine MRIs ordered for back pain and 57% of 1130 spine MRIs ordered specifically for acute back pain. The most common pathology was malignant osseous disease (2545; 43%). Across all five categories, most findings (77%–89%) were new/progressive. Odds of identifying a finding were significantly higher with total versus regional spine MRIs (P<0.001). Although only 14 patients had a positive regional MRI followed shortly by a positive total spine MRI, most of these repeat total spine MRIs (78%) identified findings outside the scope of the initial regional scan. Twenty-one patients had both computed tomography and MRI within 30 days of each other; eight (38%) had compression fractures appreciated on MRI but not on computed tomography.

Conclusions.
Our findings suggest imaging the total spine in cancer patients with back pain given higher odds of identifying malignant pathology and instances of capturing otherwise not visualized disease. Further work is warranted to confirm these findings.
Metabolic reprogramming in Nrf2-driven proliferation of normal rat hepatocytes
Authors: Kowalik Marta A. , Taguchi Keiko , Serra Marina , Caddeo Andrea , Puliga Elisabetta , Bacci Marina , Koshiba Seizo , Inoue Jin , Hishinuma Eiji , Morandi Andrea , Giordano Silvia , Perra Andrea , Yamamoto Masayuki , Columbano Amedeo 
Published: August 2023

Background and Aims:
Cancer cells reprogram their metabolic pathways to support bioenergetic and biosynthetic needs and to maintain their redox balance. In several human tumors, the Keap1-Nrf2 system controls proliferation and metabolic reprogramming by regulating the pentose phosphate pathway (PPP). However, whether this metabolic reprogramming also occurs in normal proliferating cells is unclear.

Approach and Results:
To define the metabolic phenotype in normal proliferating hepatocytes, we induced cell proliferation in the liver by 3 distinct stimuli: liver regeneration by partial hepatectomy and hepatic hyperplasia induced by 2 direct mitogens: lead nitrate (LN) or triiodothyronine. Following LN treatment, well-established features of cancer metabolic reprogramming, including enhanced glycolysis, oxidative PPP, nucleic acid synthesis, NAD+/NADH synthesis, and altered amino acid content, as well as downregulated oxidative phosphorylation, occurred in normal proliferating hepatocytes displaying Nrf2 activation. Genetic deletion of Nrf2 blunted LN-induced PPP activation and suppressed hepatocyte proliferation. Moreover, Nrf2 activation and following metabolic reprogramming did not occur when hepatocyte proliferation was induced by partial hepatectomy or triiodothyronine.

Conclusions:
Many metabolic changes in cancer cells are shared by proliferating normal hepatocytes in response to a hostile environment. Nrf2 activation is essential for bridging metabolic changes with crucial components of cancer metabolic reprogramming, including the activation of oxidative PPP. Our study demonstrates that matured hepatocytes exposed to LN undergo cancer-like metabolic reprogramming and offers a rapid and useful in vivo model to study the molecular alterations underpinning the differences/similarities of metabolic changes in normal and neoplastic hepatocytes.
A randomized trial of genotype-guided perindopril use
Authors: Lee Sang-Hak , Lee Chan Joo , Kang Yura , Park Jung Mi , Lee Ji Hyun 
Published: August 2023

Objective:
Cough caused by angiotensin-converting enzyme inhibitors (ACEIs) limits their clinical application and cardiovascular benefits. This randomized trial investigated whether genotype-guided perindopril use could reduce drug-related cough in 20 to 79-year-old individuals with hypertension.

Methods:
After screening 120 patients and randomization, 68 were assigned to genotyping (n = 41) and control (n = 27) groups. NELL1 p.Arg382Trp (rs8176786) and intron (rs10766756) genotype information was used to subdivide the genotyping group into high-risk and low-risk subgroups with at least one or no risk alleles for ACEI-related cough, respectively. The high-risk subgroup received candesartan (8 mg/day) for 6 weeks, whereas the low-risk subgroup received perindopril (4 mg/day). The control group, which was not genotyped, received perindopril (4 mg/day). The primary outcome variables were cough and moderate/severe cough; the secondary outcome variable was any adverse event.

Results:
During the 6-week period, the risk of cough was lower in the genotyping group than in the control group [five (12.2%) and nine (33.3%) participants, respectively; hazard ratio: 0.25; log-rank P = 0.017]. The moderate/severe cough risk was also lower in the genotyping group [one (2.4%) and five (18.5%) participants, respectively; hazard ratio: 0.12; log-rank P = 0.025]. Differences in cough (hazard ratio: 0.56; log-rank P = 0.32) and moderate/severe cough risk (hazard ratio: 0.26; log-rank P = 0.19) between the low-risk and control groups were not significant. The risk of total adverse events was similar between any two groups.

Conclusion:
Cough risk was lower during genotype-guided treatment than during conventional treatment. These results support the utility of NELL1 variant data in clinical decision making to personalize renin-angiotensin system blocker therapy use.

Trial Registration:
ClinicalTrials.gov number: NCT05535595 (retrospectively registered at September 7, 2022).
Systematic Review of the Diagnostic Criteria and Severity Classification for Fuchs Endothelial Corneal Dystrophy
Authors: Oie Yoshinori , Yamaguchi Takefumi , Nishida Nozomi , Okumura Naoki , Maeno Sayo , Kawasaki Ryo , Jhanji Vishal , Shimazaki Jun , Nishida Kohji 
Published: August 2023

Purpose:
There are no defined diagnostic criteria and severity classification for Fuchs endothelial corneal dystrophy (FECD), which are required for objective standardized assessments. Therefore, we performed a systematic literature review of the current diagnosis and severity classification of FECD.

Methods:
We searched the Ovid MEDLINE and Web of Science databases for studies published until January 13, 2021. We excluded review articles, conference abstracts, editorials, case reports with <5 patients, and letters.

Results:
Among 468 articles identified, we excluded 173 and 165 articles in the first and second screenings, respectively. Among the 130 included articles, 61 (47%) and 99 (76%) mentioned the diagnostic criteria for FECD and described its severity classification, respectively. Regarding diagnosis, slitlamp microscope alone was the most frequently used device in 31 (51%) of 61 articles. Regarding diagnostic findings, corneal guttae alone was the most common parameter [adopted in 23 articles (38%)]. Regarding severity classification, slitlamp microscopes were used in 88 articles (89%). The original or modified Krachmer grading scale was used in 77 articles (78%), followed by Adami's classification in six (6%). Specular microscopes or Scheimpflug tomography were used in four articles (4%) and anterior segment optical coherence tomography in one (1%).

Conclusions:
FECD is globally diagnosed by the corneal guttae using slitlamp examination, and its severity is predominantly determined by the original or modified Krachmer grading scale. Objective severity grading using Scheimpflug or anterior segment optical coherence tomography can be applied in the future innovative therapies such as cell injection therapy or novel small molecules.
Association of Methionine Synthase rs1805087 Polymorphism With Arsenic-Related Skin Pigmentary Changes: A Population-Based Case-Control Study
Authors: Huang Xiao-Yan , Xiao Yi , Jing Dan-Rong , Shen Min-Xue , Lu Li-Xia 
Published: August 2023

Objective:
Chronic arsenic exposure causes skin lesions including skin cancers, pigmentary changes, and keratosis. Genetic polymorphism in arsenic metabolism may increase susceptibility to the development of arsenic-related skin lesions. This study was performed to determine whether arsenic metabolism-related gene variants are associated with arsenic-related pigmentary changes.

Methods:
This case–control study involved 189 patients with arsenic-related pigmentary changes and 103 controls. Thirty-eight polymorphisms in 10 genes determined by mass spectrometry assay served as candidate drivers of arsenic-induced pigmentary changes. Urine and plasma arsenic levels were determined by inductively coupled plasma mass spectrometry. Hair arsenic concentrations were measured by nondispersive atomic fluorescence spectrometry. Arsenic metabolites in urine were determined using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Serum folate was measured using a folate radio assay kit. Analysis of variance, nonparametric test, or the chi-square test was selected according to the data distribution. Spearman correlation analysis was used to determine the correlation between two parameters. Logistic regression was used to estimate the effect of single-nucleotide polymorphisms.

Results:
The arsenic concentrations in urine, plasma, and hair and the urine arsenic species were not significantly different between patients and controls. Logistic regression revealed that among the polymorphisms, the methionine synthase (MTR) rs1805087 polymorphism showed a protective effect against arsenic-related pigmentary changes. In the codominant model, the adjusted odds ratio for age, sex, and ethnicity was 0.41 (95% confidence interval [CI], 0.21–0.80; P = 0.008) for the AG genotype and 0.11 (95% CI, 0.02–0.60; P = 0.012) for the GG genotype.

Conclusion:

MTR polymorphism showed a protective effect against arsenic-related pigmentary changes in the logistic regression model. The effect of MTR rs1805087 might be independent of arsenic metabolism and one-carbon metabolism. More studies are needed to clarify the biological function of MTR rs1805087 and its relationship with the etiology of arsenic-related pigmentary changes.
Full-thickness skin regeneration beneath the exposed titanium mesh in cranioplasty: Two cases report
Authors: Kan Daohong , He Xuefeng , Liu Bing , Yang Chaokun , Zou Yong 
Published: August 2023

Rationale:
Titanium mesh is one of the most widely used implant materials applied in cranioplasty; however, it has been reported to encounter the risk of progressive scalp thinning and implant exposure over time. Here we present 2 cases of exposed titanium mesh (TM) and unusual phenomena of full-thickness skin regeneration beneath the mesh.

Patient concerns:
Two patients, 1 with an 8-year and 1 with a 2-year history of implant exposure after cranial TM implantation.

Diagnoses:
The patients were diagnosed with scalp ulcers and cranial TM exposure.

Intervention:
The exposed part of the implant was removed, and the full-thickness skin beneath the mesh was directly used as functional soft tissue coverage to repair the scalp defect.

Outcomes:
Full recovery for both patients with cosmetic satisfaction.

Lessons:
Though the exact mechanism of this epithelisation phenomenon beneath the TM remains to be elucidated, it provided a feasible choice for clinicians to reconstruct the scalp’s integrity without exerting complicated procedures when dealing with similar cases.
A bibliometric systematic review of extracellular vesicles in eye diseases from 2003 to 2022
Authors: Luo Xianke , Yan Xiaoling , Yin Dan , Xia Yanting , Li Shimeng , shi Suisui , Gao Miaoran , Yang Changlu , Zhou Jian 
Published: August 2023

Background:
Extracellular vesicles (EVs) have emerged as a valuable and promising research field in eye diseases. However, there are few bibliometric studies in this area. The purpose of this study was to employ bibliometric analysis to visualize the research hotspots and trends of EVs in eye diseases and provide researchers with new perspectives for further studies.

Methods:
Articles and reviews on EVs in eye diseases published between January 1, 2003 and December 31, 2022 were retrieved from the Web of Science Core Collection. Qualitative and quantitative analysis was performed using Microsoft Excel and CiteSpace software.

Results:
In total, 790 articles were included in the analysis. Over the past 2 decades, there has been a significant increase in the number of publications on the study of EVs in eye diseases. The United States, China, and Italy made the most significant contributions to this field. The Chinese Academy of Sciences was the most productive institution, and International Journal of Molecular Sciences published the most number of articles. Proceedings of the National Academy of Sciences of the United States of America had the highest citation frequency. Beit-Yannai E had the highest output and Thery C had the highest average citation frequency among authors. The analysis of keywords revealed that the neuroprotective effects of stem cell-derived EVs and biomarkers of eye diseases are current research hotspots and frontiers in this field.

Conclusion:
This study provides a scientific perspective on EVs in eye diseases and provides valuable information for researchers to detect current research conditions, hotspots, and emerging trends for further study.
Identification of biomarkers associated with diagnosis of acute lung injury based on bioinformatics and machine learning
Authors: Jing Hekun , Chen Xiaorui , Wang Daoxin 
Published: August 2023

Background:
Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue and has a high mortality. This research was designed for the identification of novel diagnostic biomarkers for ALI and analyzing the possible association between critical genes and infiltrated immune cells.

Methods:
The study used 2 datasets (GSE2411 and GSE18341) to identify differentially expressed genes (DEGs) between 2 groups. Then we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to identify the functions of these DEGs. The study also used SVM-recursive feature elimination analysis and least absolute shrinkage and selection operator regression model to screen possible markers. The study further analyzed immune cell infiltration via CIBERSORT. Gene Set Enrichment Analysis was used to explore the molecular mechanism of the critical genes.

Results:
DEGs were identified between 2 groups. In total, 690 DEGs were obtained: 527 genes were upregulated and 163 genes were downregulated. We identified PDZK1IP1, CCKAR, and CXCL2 as critical genes. And we then found that these critical genes correlated with Mast Cells, Neutrophil Cells, M1 Macrophage, dendritic cell Actived, Eosinophil Cells, B Cells Naive, Mast Cells, and dendritic cell Immature. Furthermore, we investigated the specific signaling pathways involved in key genes and derived some potential molecular mechanisms by which key genes affect disease progression by use of Gene Set Enrichment Analysis. Moreover, we predict transcription factors. Also, we obtained critical gene-related microRNAs through the targetscan database, and visualized the microRNA network of the genes.

Conclusion:
Our findings might provide some novel clue for the exploration of novel markers for ALI diagnosis. The critical genes and their associations with immune infiltration may offer new insight into understanding ALI developments.
Association between pain burden and presence of any limitation among older adults (≥50 years of age) with pain who used opioids in the United States: Cross-sectional study using 2020 medical expenditure panel survey
Authors: Aqel Osama , Agu Uchechukwu , Almatruk Ziyad , Axon David R. 
Published: August 2023

This study aimed to assess the association between pain burden and presence of any limitation among older adults (≥50 years of age) with pain who used opioids in the United States.
This cross-sectional study used 2020 Medical Expenditure Panel Survey data and included all adults aged 50 or older, who were alive for the 2020 calendar year, used an opioid at least once in the calendar year, and reported having pain in the past 4 weeks. Unadjusted and adjusted logistic regression models were developed to assess the association between any limitation (AL) (yes or no), pain burden (extremely, quite a bit, moderately, or little bit) and the control variables among a nationally representative sample of United States adults. A total of 844 of the 27,805 participants included in the dataset were eligible for the study. Of these, 71.2% (95% confidence interval (CI) = 67.2, 75.1%) reported the presence of AL. The adjusted logistic regression analysis showed that having extreme, quite a bit, or moderate pain (vs little pain) was associated with 10.30 (95% CI = 3.87, 27.40), 5.07 (95% CI = 2.77, 9.30), and 2.49 (95% CI = 1.40, 4.45), respectively, times greater odds of having AL. Furthermore, being unemployed (vs employed; adjusted odds ratio (aOR) = 5.26, 95% CI = 2.94, 9.09%), unmarried (vs married; aOR = 1.92, 95% CI = 1.12, 3.33%), having poor overall health (vs good overall health; aOR = 2.08, 95% CI = 1.08, 4.17), and residing in the Midwest (vs West; aOR = 2.04, 95% CI = 1.10, 3.80) were associated with greater odds of having AL. Extreme, quite a bit, and moderate pain burden were significantly associated with greater odds of reporting AL compared to little pain burden. Developing effective pain management strategies that address not only pain relief but also functional improvement among this population is of importance. Future research could then be conducted to determine the most effective pain management strategies that will provide pain relief and improve their functional abilities.
Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials
Authors: Liu Xin-Xiu , Han Yan-Hong , Kuang Bo-Hua , Lin Guo-He , Wang Bi-Cheng 
Published: August 2023

Background:
Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS).

Methods:
Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes.

Results:
In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20–1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05–1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52–1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54–1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments.

Conclusion:
Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.
Systematic reviews and meta-analyses on androgen administration in humans: an umbrella review
Authors: Chegeni Razieh , Pallesen Ståle , Weldemariam Hailemariam , Sagoe Dominic 
Published: August 2023

Purpose of review
The present umbrella review systematically searches and synthesizes recent (2021–2023) systematic reviews and meta-analyses (SRMA) on androgen administration in humans.

Recent findings
Results from 19 SRMA are synthesized. Four themes were identified: market for androgens, prevalence of androgen abuse, psychological effects of androgens, and clinical/therapeutic effects of androgens. One of three androgens on the illicit market are fake or substandard. Whereas one of three androgen users experiences dependence and various serious disorders, only one of three androgen users seeks physician support. Additionally, androgen administration increases self-reported aggression in healthy male individuals, and abuse positively correlates with interpersonal violence. Furthermore, androgen therapy is beneficial in treating persons suffering from various chronic diseases.

Summary
In this umbrella review, we identified 19 SRMA on androgen use and abuse. Results show a high prevalence of fake androgens on the illicit market, a high prevalence of androgen abuse and dependence, and that a huge proportion of androgen users tend to avoid seeking support from clinicians. Also, androgen administration increases self-reported aggression among healthy male, and there is a positive correlation between androgen abuse and violent behavior. Finally, androgens have multiple therapeutic effects on various pathology.
Optimal combination therapy for metastatic hormone-sensitive prostate cancer: new evidence, challenges and unanswered questions
Authors: Zattoni Fabio , Rajwa Pawel , Gandaglia Giorgio 
Published: August 2023

Purpose of review
To evaluate the evidence supporting treatment intensification in mHSPC, with a focus on possible indications for treatment in each clinical setting.

Recent findings
There is a growing armamentarium of treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC). These include combinations of treatments such as androgen deprivation therapy (ADT), docetaxel, and new antiandrogenic therapies. Treatment intensification with chemotherapy or newer hormonal agents may improve patient's oncologic outcomes, but it can also come with additional toxicities and costs. Therefore, we need to take into account individual patient factors and preferences when deciding on the optimal combination therapy. Additionally, ongoing research is needed to identify biomarkers and new image techniques that can predict response to treatment and identify the best candidate for each treatment.

Summary
Challenges and unanswered questions regarding treatment intensification and de-intensification are still present. Further studies are still needed to identify which patients would benefit most from this approach to improve quality of life without compromising overall survival outcomes.