bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biologics for Treatment of Pityriasis Rubra Pilaris: A Literature Review
Authors: Chandy Rithi J. , Chokshi Aditi , Tan Isabella , Feldman Steven R. 
Published: March 2024

Objective: To describe the published efficacy and adverse event rates associated with existing biologics for the treatment of pityriasis rubra pilaris (PRP). Data Sources: A literature review using the PubMed database (January 1990-July 2023) was conducted. Multiple search combinations were conducted using “pityriasis rubra pilaris” and various biologics as keywords to identify relevant articles. Study Selection and Data Extraction: Inclusion criteria included all study types that were published within the past 30 years in English and mentioned at least one biologic and PRP. A preliminary search yielded a total of 499 results. After screening using inclusion and exclusion criteria, 77 relevant articles (69 case reports, 5 case series, 2 clinical trials, and 1 retrospective analysis) were analyzed. Data Synthesis: TNF-α inhibitors have been evaluated and are effective in treating PRP. However, recent treatment with anti-interleukin (IL)-17 and anti-IL-23 therapies such as ustekinumab, secukinumab, and ixekizumab are emerging as new treatment options with a mean improvement in PRP Area and Severity Index scores, change in severity of erythema, scaling, and thickness of PRP lesions. From initial clinical trials, secukinumab and ixekizumab are promising treatment options for achieving remission. Relevance to Patient Care and Clinical Practice: This review compares the efficacy for numerous biologics and a discussion to guide clinicians on benefits and risks in choosing a biologic for PRP patients. Conclusions: Biologics may be a favourable treatment option leading to greater patient adherence due to reduced dosing frequencies, improvement in quality of life, and reduction in frequency and severity of flares.
Effects of Endoscopic Sinus Surgery on Olfactory Bulb Volume among Patients with Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis
Authors: Jiang Xincen , Huang Tianhao , Chang Feifan , Song Yu , Wu Dawei 
Published: March 2024

Background Endoscopic sinus surgery (ESS) could significantly improve olfactory function among patients with chronic rhinosinusitis (CRS). This study aimed to perform a meta-analysis to evaluate the effect of ESS on the olfactory bulb volume (OBV) among patients with CRS. Methods A systemic search of PubMed, Medline, Embase, Web of Science, and other databases was conducted to identify studies assessing OBV changes in patients with CRS after ESS utilizing magnetic resonance imaging. Results A total of four studies with 168 participants were included. Comparing the changes in OBV of patients with CRS before and after surgery within 3-6 months, the ESS significantly improved the overall OBV ( P = 0.005, I2 = 66%), with the left OBV increased by 5.57mm3 ( P = 0.84, I2 = 0%), and the right OBV increased by 8.63mm3 ( P = 0.09, I2 = 53%). A difference in OBV persists between healthy controls and patients with CRS 3-6 months after ESS. The overall OBV of patients with CRS after ESS was significantly smaller than controls (mean difference = -3.84, P = 0.04), with a mean difference of 4.13mm3 on the left side ( P = 0.72, I2 = 0%), and a mean difference of 3.22mm3 on the right side ( P = 0.0001, I2 = 89%). Conclusions ESS significantly increases the OBV among patients with CRS.
Loss of GABARAP mediates resistance to immunogenic chemotherapy in multiple myeloma
Authors: Gulla Annamaria , Morelli Eugenio , Johnstone Megan , Turi Marcello , Samur Mehmet K. , Botta Cirino , Cifric Selma , Folino Pietro , Vinaixa Delaney , Barello Francesca , Clericuzio Cole , Favasuli Vanessa Katia , Maisano Domenico , Talluri Srikanth , Prabhala Rao , Bianchi Giada , Fulciniti Mariateresa , Wen Kenneth , Kurata Keiji , Liu Jiye , Penailillo Johany , Bragoni Alberto , Sapino Anna , Richardson Paul G. , Chauhan Dharminder , Carrasco Ruben D. , Hideshima Teru , Munshi Nikhil C. , Anderson Kenneth C. 
Published: March 2024

Abstract
Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant antitumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and creates durable therapeutic responses in patients. However, eventual relapse and resistance to bortezomib appear inevitable. Here, by integrating patient transcriptomic data with an analysis of calreticulin (CRT) protein interactors, we found that GABA type A receptor–associated protein (GABARAP) is a key player whose loss prevented tumor cell death from being perceived as immunogenic after bortezomib treatment. GABARAP is located on chromosome 17p, which is commonly deleted in patients with high risk MM. GABARAP deletion impaired the exposure of the eat-me signal CRT on the surface of dying MM cells in vitro and in vivo, thus reducing tumor cell phagocytosis by dendritic cells and the subsequent antitumor T-cell response. Low GABARAP was independently associated with shorter survival in patients with MM and reduced tumor immune infiltration. Mechanistically, we found that GABARAP deletion blocked ICD signaling by decreasing autophagy and altering Golgi apparatus morphology, with consequent defects in the downstream vesicular transport of CRT. Conversely, upregulating autophagy using rapamycin restored Golgi morphology, CRT exposure, and ICD signaling in GABARAPKO cells undergoing bortezomib treatment. Therefore, coupling an ICD inducer, such as bortezomib, with an autophagy inducer, such as rapamycin, may improve patient outcomes in MM, in which low GABARAP in the form of del(17p) is common and leads to worse outcomes.
Effects of mifepristone on adipocyte differentiation in mouse 3T3-L1 cells
Authors: Hashimoto Takeshi , Hirano Katsuya 
Published: March 2024

Abstract
Background
Both glucocorticoid receptor and peroxisome proliferator-activated receptor-γ (PPARγ) play a critical role in adipocyte differentiation. Mifepristone is not only an antagonist of the glucocorticoid receptor but also an agonist of PPARγ. Therefore, the present study investigated the effect of mifepristone on adipocyte differentiation.

Methods
Mouse 3T3-L1 cells were used as a model for adipocyte differentiation. The lipid droplet formation was evaluated with Bodipy493/503 staining and the expression of adipocyte markers [adiponectin and adipocyte fatty acid binding protein-4 (Fabp4)] was evaluated with quantitative PCR and immunoblot analyses for indication of adipocyte differentiation. siRNA and neutralizing antibodies were used to elucidate the molecular mechanism of mifepristone-induced adipocyte differentiation. Luciferase reporter assay was used to examine the effect of mifepristone on the promoter activity of PPAR-response element (PPRE). The DNA microarray analysis was used to characterize the transcriptome of the mifepristone-induced adipocytes. In vivo adipogenic effect of mifepristone was examined in mice.

Results
Mifepristone not only enhanced adipocyte differentiation induced by the conventional protocol consisting of insulin, dexamethasone and 3-isobutyl-1-methylxanthine but also induced adipocyte differentiation alone, as evidenced by lipid droplets formation and induction of the expression of adiponectin and Fabp4. These effects were inhibited by an adiponectin-neutralizing antibody and a PPARγ antagonist. Mifepristone activated the promoter activity of PPRE in a manner sensitive to PPARγ antagonist. A principal component analysis (PCA) of DNA microarray data revealed that the mifepristone-induced adipocytes represent some characteristics of the in situ adipocytes in normal adipose tissues to a greater extent than those induced by the conventional protocol. Mifepristone administration induced an increase in the weight of epididymal, perirenal and gluteofemoral adipose tissues.

Conclusions
Mifepristone alone is capable of inducing adipocyte differentiation in 3T3-L1 cells and adipogenesis in vivo. PPARγ plays a critical role in the mifepristone-induced adipocyte differentiation. Mifepristone-induced adipocytes are closer to the in situ adipocytes than those induced by the conventional protocol. The present study proposes a single treatment with mifepristone as a novel protocol to induce more physiologically relevant adipocytes in 3T3-L1 cells than the conventional protocol.
Towards a unified medical microbiome ecology of the OMU for metagenomes and the OTU for microbes
Authors: Ma Zhanshan 
Published: March 2024

Abstract
Background
Metagenomic sequencing technologies offered unprecedented opportunities and also challenges to microbiology and microbial ecology particularly. The technology has revolutionized the studies of microbes and enabled the high-profile human microbiome and earth microbiome projects. The terminology-change from microbes to microbiomes signals that our capability to count and classify microbes (microbiomes) has achieved the same or similar level as we can for the biomes (macrobiomes) of plants and animals (macrobes). While the traditional investigations of macrobiomes have usually been conducted through naturalists’ (Linnaeus & Darwin) naked eyes, and aerial and satellite images (remote-sensing), the large-scale investigations of microbiomes have been made possible by DNA-sequencing-based metagenomic technologies. Two major types of metagenomic sequencing technologies—amplicon sequencing and whole-genome (shotgun sequencing)—respectively generate two contrastingly different categories of metagenomic reads (data)—OTU (operational taxonomic unit) tables representing microorganisms and OMU (operational metagenomic unit), a new term coined in this article to represent various cluster units of metagenomic genes.

Results
The ecological science of microbiomes based on the OTU representing microbes has been unified with the classic ecology of macrobes (macrobiomes), but the unification based on OMU representing metagenomes has been rather limited. In a previous series of studies, we have demonstrated the applications of several classic ecological theories (diversity, composition, heterogeneity, and biogeography) to the studies of metagenomes. Here I push the envelope for the unification of OTU and OMU again by demonstrating the applications of metacommunity assembly and ecological networks to the metagenomes of human gut microbiomes. Specifically, the neutral theory of biodiversity (Sloan’s near neutral model), Ning et al.stochasticity framework, core-periphery network, high-salience skeleton network, special trio-motif, and positive-to-negative ratio are applied to analyze the OMU tables from whole-genome sequencing technologies, and demonstrated with seven human gut metagenome datasets from the human microbiome project.

Conclusions
All of the ecological theories demonstrated previously and in this article, including diversity, composition, heterogeneity, stochasticity, and complex network analyses, are equally applicable to OMU metagenomic analyses, just as to OTU analyses. Consequently, I strongly advocate the unification of OTU/OMU (microbiomes) with classic ecology of plants and animals (macrobiomes) in the context of medical ecology.
DAE-CFR: detecting microRNA-disease associations using deep autoencoder and combined feature representation
Authors: Liu Yanling , Zhang Ruiyan , Dong Xiaojing , Yang Hong , Li Jing , Cao Hongyan , Tian Jing , Zhang Yanbo 
Published: March 2024

Abstract
Background
MicroRNA (miRNA) has been shown to play a key role in the occurrence and progression of diseases, making uncovering miRNA-disease associations vital for disease prevention and therapy. However, traditional laboratory methods for detecting these associations are slow, strenuous, expensive, and uncertain. Although numerous advanced algorithms have emerged, it is still a challenge to develop more effective methods to explore underlying miRNA-disease associations.

Results
In the study, we designed a novel approach on the basis of deep autoencoder and combined feature representation (DAE-CFR) to predict possible miRNA-disease associations. We began by creating integrated similarity matrices of miRNAs and diseases, performing a logistic function transformation, balancing positive and negative samples with k-means clustering, and constructing training samples. Then, deep autoencoder was used to extract low-dimensional feature from two kinds of feature representations for miRNAs and diseases, namely, original association information-based and similarity information-based. Next, we combined the resulting features for each miRNA-disease pair and used a logistic regression (LR) classifier to infer all unknown miRNA-disease interactions. Under five and tenfold cross-validation (CV) frameworks, DAE-CFR not only outperformed six popular algorithms and nine classifiers, but also demonstrated superior performance on an additional dataset. Furthermore, case studies on three diseases (myocardial infarction, hypertension and stroke) confirmed the validity of DAE-CFR in practice.

Conclusions
DAE-CFR achieved outstanding performance in predicting miRNA-disease associations and can provide evidence to inform biological experiments and clinical therapy.
IL-1β induced down-regulation of miR-146a-5p promoted pyroptosis and apoptosis of corneal epithelial cell in dry eye disease through targeting STAT3
Authors: Li Xuejiao , Peng Hua , Kang Jianshu , Sun Xiaomei , Liu Jian 
Published: March 2024

Abstract
Aim
To elaborate the underlying mechanisms by which IL-1β promote progression of Dry eye disease(DED) through effect on pyroptosis and apoptosis of corneal epithelial cells(CECs).

Methods
400 mOsM solutions were used to establish the DED model (hCECs- DED). RT-qPCR was performed to measure IL-1β mRNA and miR-146a-5p in CECs. Western blotting was performed to measure STAT3, GSDMD, NLRP3, and Caspase-1 levels. Cell counting kit-8 assay was adopted to check cell viability. Apoptosis was detected by flow cytometry. ELISAs were performed to determine IL-18, IL-33 and LDH. The luciferase test detects targeting relationships.

Results
After treatment with 400 mOsM solution, cell viability decreased and apoptosis increased. Compared with hCECs, IL-1β was increased and miR-146a-5p was decreased in hCECs-DED. At the same time, GSDMD, NLRP3, Caspase-1, IL-18, IL-33 and LDH were significantly higher in hCECs-DED than in hCECs, while IL-1β silencing reversed this effect. In addition, IL-1β negatively regulated miR-146a-5p. MiR-146a-5p mimics eliminated the inhibition of hCECs-DED pyroptosis and apoptosis caused by IL-1β silencing. At the same time, miR-146a-5p reduced STAT3 levels in hCECs.

Conclusion
Highly expressed IL-1β promoted pyroptosis and apoptosis of hCECs- DED through downregulated miR-146a-5p and inhibited STAT3.
Who chooses “healthy” meals? An analysis of lunchtime meal quality in a workplace cafeteria
Authors: Bullock Sally L. , Winthrop Hilary M. , Hales Derek , Lin Feng-Chang , Yang Yumei , Ammerman Alice S. , Viera Anthony J. 
Published: March 2024

Abstract
Background
The workplace can play an important role in shaping the eating behaviors of U.S. adults. Unfortunately, foods obtained in the workplace tend to be low in nutritional quality. Questions remain about the best way to approach the promotion of healthy food purchases among employees and to what extent health promotion activities should be tailored to the demographic characteristics of the employees. The purpose of this study was to (1) assess the nutritional quality of lunchtime meal purchases by employees in cafeterias of a large organization, (2) examine associations between lunchtime meal quality selection and the demographic characteristics of employees, and (3) determine the healthfulness of foods and beverages offered in the cafeterias of this organization.

Methods
A cross-sectional analysis was conducted using secondary data from a food labeling study implemented in three worksite cafeterias. Demographic data was collected via surveys and meal data was collected using a photo capture system for 378 participants. The Healthy Eating Index 2015 (HEI-2015) was used to determine meal quality and a total score for the menu of options available in the cafeterias during the study period. Summary statistics were generated, and the analysis of variance (ANOVA) was used to compare the HEI-2015 scores between groups.

Results
The mean HEI-2015 total score for the menu items offered (n = 1,229) in the cafeteria during the study period was 63.1 (SD = 1.83). The mean HEI-2015 score for individual lunchtime meal observations (n = 378) was 47.1 (SD = 6.8). In general, HEI-2015 total scores were higher for non-smokers, individuals who self-identified as Asian, had higher physical activity levels, scored higher on numeracy and literacy assessments, and reported higher education levels, incomes, and health status.

Conclusions
The overall HEI-2015 scores indicate that the menu of options offered in the cafeterias and individual meal selections did not align with the Dietary Guidelines for Americans, and there were significant associations between average lunchtime meal quality scores and several demographic characteristics. These results suggest that healthy eating promotion activities in workplaces may need to be tailored to the demographic characteristics of the employees, and efforts to improve the food environment in the workplace could improve meal quality for all employees.
Efficacy of optimal nutraceutical combination in treating PCOS characteristics: an in-silico assessment
Authors: Saxena Abha , Sherkane Manali , Bhoite Rachana , Sadananda Manasa Premasudha , Satyavrat Vinita , Kareenhalli Venkatesh 
Published: March 2024

Abstract
Background
Polycystic ovary syndrome (PCOS) is a serious health condition affecting women of reproductive age. High prevalence of PCOS and associated metabolic complications needs effective treatment and management. This study evaluated the efficacy of optimal nutraceutical combinations in improving PCOS characteristics using system biology-based mathematical modelling and simulation.

Methods
A shortlisting of eight potent nutraceuticals was carried out with literature search. Menstrual cycle model was used to perform simulations on an in-silico population of 2000 individuals to test individual and combined effects of shortlisted nutraceuticals on five PCOS characteristics [oligomenorrhea, anovulation, hirsutism, infertility, and polycystic ovarian morphology (PCOM)] for a duration of 6 months. Efficacy was tested across lean and obese phenotypes and age groups.

Results
Individual assessment of nutraceuticals revealed seven most potent compounds. Myo-inositol among them was observed to be the most effective in alleviating the PCOS characteristics. The in-silico population analysis showed that the combination of melatonin and ALA along with myo-inositol was efficacious in restoring the hormonal balance across age-groups and Body Mass Index (BMI) categories.

Conclusion
Supplementation with the combination of myo-inositol, melatonin, and ALA demonstrated potential in managing PCOS symptoms in our in-silico analysis of a heterogeneous population, including lean and obese phenotypes across various severities and age groups, over a 6-month period. Future clinical studies are recommended to validate these findings.
Predictors of apical periodontitis in root canal treated teeth from an adult Nepalese subpopulation: a cross-sectional study
Authors: Hussain Md. Asdaq , Singh Shailendra Kumar , Naz Shazia , Haque Merazul , Shah Harish Kumar , Singh Abanish 
Published: March 2024

Abstract
Background
Endodontic literature search revealed that no study has been conducted to evaluate the prevalence of apical periodontitis (AP) in root canal treated teeth from an adult Nepalese population of Madhesh Province. Consequently, little is known about the extent and risk factors associated with it. This study aimed to determine AP prevalence in root canal treated teeth from an adult Nepalese subpopulation and to analyze the related risk factors including age, sex, tooth type, type of coronal restoration and quality of root canal treatment and coronal restoration as predictors of AP.

Methods
Digital panoramic radiographs were evaluated. Periapical status of 300 root canal-treated teeth was scored by using the periapical index. The quality of root canal treatment and coronal restorations were categorized as adequate or inadequate through radiographic and clinical evaluation. The data were analyzed using univariate and multivariate logistic regression models.

Results
Prevalence of AP in the present study was 31.7%. In 45.7% of the treated teeth, quality of root canal treatment was adequate whereas 46% of the cases had adequate coronal restorations. Multivariate logistic regression analysis revealed statistically significant associations and remarkably increased risk for AP in teeth with inadequate root canal treatment (odds ratio [OR] = 7.92; 95% CI: 3.96–15.82; p < 0.001) whereas lower risk for AP was found in females (OR = 0.51; 95% CI: 0.28–0.90; p = 0.021) and in teeth restored with crown (OR = 0.22; 95% CI: 0.09–0.51; p < 0.001) and filling (OR = 0.18; 95% CI: 0.08–0.42; p < 0.001). Quality of coronal restoration, tooth type and age of the patient were not found to be the predictors of AP.

Conclusions
Within the limits of this study, a high prevalence of AP and poor overall quality of root canal treatment and coronal restoration was found in the subpopulation studied. Quality of root canal treatment, type of coronal restoration and sex of the patient are significant predictors of possible AP development in root canal treated teeth. Substantial efforts are needed to improve the endodontic treatment standards.
Large language models for generating medical examinations: systematic review
Authors: Artsi Yaara , Sorin Vera , Konen Eli , Glicksberg Benjamin S. , Nadkarni Girish , Klang Eyal 
Published: March 2024

Abstract
Background
Writing multiple choice questions (MCQs) for the purpose of medical exams is challenging. It requires extensive medical knowledge, time and effort from medical educators. This systematic review focuses on the application of large language models (LLMs) in generating medical MCQs.

Methods
The authors searched for studies published up to November 2023. Search terms focused on LLMs generated MCQs for medical examinations. Non-English, out of year range and studies not focusing on AI generated multiple-choice questions were excluded. MEDLINE was used as a search database. Risk of bias was evaluated using a tailored QUADAS-2 tool.

Results
Overall, eight studies published between April 2023 and October 2023 were included. Six studies used Chat-GPT 3.5, while two employed GPT 4. Five studies showed that LLMs can produce competent questions valid for medical exams. Three studies used LLMs to write medical questions but did not evaluate the validity of the questions. One study conducted a comparative analysis of different models. One other study compared LLM-generated questions with those written by humans. All studies presented faulty questions that were deemed inappropriate for medical exams. Some questions required additional modifications in order to qualify.

Conclusions
LLMs can be used to write MCQs for medical examinations. However, their limitations cannot be ignored. Further study in this field is essential and more conclusive evidence is needed. Until then, LLMs may serve as a supplementary tool for writing medical examinations. 2 studies were at high risk of bias. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.