bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin, paclitaxel, and pembrolizumab followed by pembrolizumab maintenance for primary treatment of incompletely resected epithelial ovarian cancer
Authors: Uyar Denise , Michener Chad M. , Bishop Erin , Hopp Elizabeth , Simpson Pippa , Zhang Liyun , Rader Janet S. , Rose Peter G. , Mahdi Haider S. , Debernardo Robert , Christian Qiana , Bradley William 
Published: February 2024

ObjectiveIncompletely resected epithelial ovarian cancer represents a poor prognostic subset of patients. Novel treatment strategies are needed to improve outcomes for this population. We evaluated a treatment strategy combining platinum-based chemotherapy with pembrolizumab followed by pembrolizumab maintenance therapy in the first-line treatment after incomplete resection of epithelial ovarian cancer patients.MethodsThis was a single-arm, non-randomized pilot study of carboplatin, taxane, and immune checkpoint inhibitor, pembrolizumab, followed by 12 months of maintenance pembrolizumab in patients with incompletely resected epithelial ovarian cancer (EOC).ResultsA total of 29 patients were enrolled and evaluated for efficacy and safety. The best response to therapy was complete response in 16 (55%) patients, partial response in 9 (31%) patients, and 3 (10%) patients with progression of disease. The median progression-free survival (PFS) was 13.2 months. Grade 3 and 4 toxicities occurred in 20% of patients. In all, 7 patients discontinued therapy due to adverse events. Quality-of-life scores remained high during therapy. Response to therapy did not correlate with PD-L1 tumor expression.ConclusionsCombination platinum–taxane therapy with pembrolizumab did not increase median progression-free survival in this cohort of patients.Key messageEOC is an immunogenic disease, but immune checkpoint inhibitor therapy has yet to impact outcomes. The current study utilized pembrolizumab in combination with standard chemotherapy followed by a maintenance treatment strategy in incompletely resected EOC. Progression-free survival was not extended in this poor prognostic group with combined chemotherapy and immunotherapy.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT 027766582.
The absolute number of small and diminutive adenomas with high-grade dysplasia is substantially higher compared with large adenomas: a retrospective pooled study
Authors: Zhang Jiancheng , Sun Huajun , Xiong Fei , Lei Shan , Zhou Guanyu , Xiao Xun , Liu Lin , Wang Pu 
Published: February 2024

IntroductionThe risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (&lt;10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population.MethodsThe pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category.ResultsAmong a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P &lt; 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P &lt; 0.0001). The combined number of HGD presented a trend negatively correlated to size.ConclusionsOur data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer.Systematic Review Registrationhttp://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.
Proteomic and metabolomic signatures of rectal tumor discriminate patients with different responses to preoperative radiotherapy
Authors: Wojakowska Anna , Marczak Lukasz , Zeman Marcin , Chekan Mykola , Zembala-Nożyńska Ewa , Polanski Krzysztof , Strugała Aleksander , Widlak Piotr , Pietrowska Monika 
Published: February 2024

BackgroundNeoadjuvant radiotherapy (neo-RT) is widely used in locally advanced rectal cancer (LARC) as a component of radical treatment. Despite the advantages of neo-RT, which typically improves outcomes in LARC patients, the lack of reliable biomarkers that predict response and monitor the efficacy of therapy, can result in the application of unnecessary aggressive therapy affecting patients’ quality of life. Hence, the search for molecular biomarkers for assessing the radio responsiveness of this cancer represents a relevant issue.MethodsHere, we combined proteomic and metabolomic approaches to identify molecular signatures, which could discriminate LARC tumors with good and poor responses to neo-RT.ResultsThe integration of data on differentially accumulated proteins and metabolites made it possible to identify disrupted metabolic pathways and signaling processes connected with response to irradiation, including ketone bodies synthesis and degradation, purine metabolism, energy metabolism, degradation of fatty acid, amino acid metabolism, and focal adhesion. Moreover, we proposed multi-component panels of proteins and metabolites which could serve as a solid base to develop biomarkers for monitoring and predicting the efficacy of preoperative RT in rectal cancer patients.ConclusionWe proved that an integrated multi-omic approach presents a valid look at the analysis of the global response to cancer treatment from the perspective of metabolomic reprogramming.
Clinical efficacy of plasmid encoding p62/SQSTM1 (Elenagen) in combination with gemcitabine in patients with platinum-resistant ovarian cancer: a randomized controlled trial
Authors: Krasny Sergei , Baranau Yauheni , Polyakov Sergey , Zharkova Ekaterina , Streltsova Olga , Filimonava Aliona , Siarheyeva Volha , Kazlouskaya Sviatlana , Khorau Anton , Gabai Vladimir , Shneider Alexander 
Published: February 2024

BackgroundThe purpose of this trial is to evaluate the safety and efficacy of ELENAGEN, a novel anticancer therapeutic DNA plasmid encoding p62/SQSTM1 protein, as an adjuvant to chemotherapy with gemcitabine (GEM) in patients with advanced platinum-resistant ovarian cancer.MethodsThis open-label prospective randomized study with two arms. GEM (1000 mg/m2) on days 1 and 8 every 3 weeks was administered in both arms: in the Chemo arm (n = 20), GEM was the only treatment, and in the ELENAGEN arm (n = 20), GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was safety. Antitumor activity was assessed by RECIST 1.1, and criteria safety was assessed according to NCI CTCAE version 5.0.ResultsAccording to the cutoff data, the median follow-up was 13.8 months. There were no serious adverse events related to ELENAGEN treatment. The median PFS was 2.8 and 7.2 months in the Chemo and ELENAGEN arms, respectively (p Log-Rank = 0.03). Notably, at the time of cutoff, 9 patients (45%) in the ELENAGEN arm did not progress, with the longest PFS recorded thus far being 24 months. Subgroup analysis of patients in both arms demonstrated high efficacy of ELENAGEN in patients with worse prognostic factors: high pretreatment levels of CA125 and progression after platinum-free interval &lt;3 months.ConclusionsThe addition of ELENAGEN to gemcitabine is effective in patients with platinum-resistant ovarian cancer, including those with a worse prognosis.Clinical trial registrationhttps://www.clinicaltrials.gov/study/NCT05979298, identifier NCT05979298, 2023-08-07.
Clinical significance of bone marrow involvement by immunoglobulin gene rearrangement in de novo diffuse large B-cell lymphoma: a multicenter retrospective study
Authors: Kim Yu Ri , Shin Ho Jin , Yhim Ho-Young , Yang Deok-Hwan , Park Yong , Lee Ji Hyun , Lee Won-Sik , Do Young Rok , Mun Yeung-Chul , Kim Dae Sik , Kim Jin Seok 
Published: February 2024

BackgroundBone marrow (BM) involvement is an indicator of a poor prognosis in diffuse large B-cell lymphoma (DLBCL); however, few studies have evaluated the role of immunoglobulin gene rearrangement (IgR) in detecting BM involvement.MethodsWe evaluated the clinical characteristics and treatment outcomes of patients with DLBCL based on histological BM involvement or positive BM IgR using polymerase chain reaction or next-generation sequencing. We also investigated the role of consolidative upfront autologous hematopoietic stem cell transplantation (ASCT) in patients with DLBCL and BM involvement.ResultsAmong 624 patients, 123 (19.7%) with histological BM involvement and 88 (17.5%) with positive IgR in histologically negative BM had more advanced disease characteristics. Overall (OS) and progression-free (PFS) survival was better for patients with negative BM histology and negative IgR than that in patients with histological BM involvement (P = 0.050 and P &lt; 0.001, respectively) and positive IgR with negative BM histology (P = 0.001 and P = 0.005, respectively). Survival rates did not differ among 82 (13.1%) patients who were treated with upfront ASCT and had histological BM involvement or positive IgR with negative BM histology. The survival outcomes were worse for patients who were not treated with upfront ASCT and for those with histological BM involvement or positive IgR, than for those with negative BM histology and negative IgR.ConclusionPatients diagnosed with DLBCL and BM involvement based on histology or IgR had aggressive clinical features and poor survival. Upfront ASCT mitigated poor prognosis due to BM involvement.
The role of contextual factors in avenues to recover from gambling disorder: a scoping review
Authors: Johannessen Dagny Adriaenssen , Overå Stian , Arnevik Espen Ajo 
Published: February 2024

IntroductionRecovery from complex conditions such as gambling disorders (GD) often entail considerable change and require a range of adaptable interventions in the health care system. Outcomes from such avenues to change are influenced by multifarious contextual factors, which are less frequently considered in treatment outcome studies. Accordingly, this scoping review aims to map the level of evidence and explore how contextual factors influence the provision and outcomes of GD interventions.MethodsA systematic search in selected health and social science research databases yielded a total of 2.464 unique references. The results were screened in three selection steps—titles (n = 2.464), abstracts (n = 284) and full-text (n = 104). The scoping approach was applied to provide a narrative account of the final included references (n = 34).Results and discussionFindings suggest that the research on GD treatment is in the early stages of development. Additionally, studies on GD interventions are characterized by cultural biases (Region and ethnicity and Gender perspectives), while three key elements are described as successful avenues to recover from GD (Competence, Perception and Utilization). In line with these findings, proposals for future research and treatment designs are made.
Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice
Authors: Chen Simin , Li Mengjia , Tong Changqing , Wang Yanan , He Jiahui , Shao Qi , Liu Yan , Wu Ying , Song Yuehan 
Published: February 2024

BackgroundThe gut-brain axis and gut microbiota have emerged as key players in emotional disorders. Recent studies suggest that alterations in gut microbiota may impact psychiatric symptoms through brain miRNA along the gut-brain axis. However, direct evidence linking gut microbiota to the pathophysiology of generalized anxiety disorder (GAD) via brain miRNA is limited. In this study, we explored the effects of fecal microbiota transplantation (FMT) from GAD donors on gut microbiota and prefrontal cortex miRNA in recipient mice, aiming to understand the relationship between these two factors.MethodsAnxiety scores and gut microbiota composition were assessed in GAD patients, and their fecal samples were utilized for FMT in C57BL/6J mice. Anxiety-like behavior in mice was evaluated using open field and elevated plus maze tests. High-throughput sequencing of gut microbiota 16S rRNA and prefrontal cortex miRNA was performed.ResultsThe fecal microbiota of GAD patients exhibited a distinct microbial structure compared to the healthy group, characterized by a significant decrease in Verrucomicrobia and Akkermansia, and a significant increase in Actinobacteria and Bacteroides. Subsequent FMT from GAD patients to mice induced anxiety-like behavior in recipients. Detailed analysis of gut microbiota composition revealed lower abundances of Verrucomicrobia, Akkermansia, Bifidobacterium, and Butyricimonas, and higher abundances of Deferribacteres, Allobaculum, Bacteroides, and Clostridium in mice that received FMT from GAD patients. MiRNA analysis identified five key miRNAs affecting GAD pathogenesis, including mmu-miR-10a-5p, mmu-miR-1224-5p, mmu-miR-218-5p, mmu-miR-10b-5p, and mmu-miR-488-3p. Notably, mmu-miR-488-3p showed a strong negative correlation with Verrucomicrobia and Akkermansia.ConclusionThis study demonstrates that anxiety-like behavior induced by human FMT can be transmitted through gut microbiota and is associated with miRNA expression in the prefrontal cortex. It is inferred that the reduction of Akkermansia caused by FMT from GAD patients leads to the upregulation of mmu-miR-488-3p expression, resulting in the downregulation of its downstream target gene Creb1 and interference with its related signaling pathway. These findings highlight the gut microbiota’s crucial role in the GAD pathophysiology.
The association between polychlorinated dibenzo-p-dioxin exposure and cancer mortality in the general population: a cohort study
Authors: Zheng Lei , Zhang Xianli , Gao Zhe , Zhong Chunyu , Qiu Dezhi , Yan Qing 
Published: February 2024

IntroductionEarlier research has indicated that being exposed to polychlorinated dibenzo-p-dioxins (PCDDs) in the workplace can heighten the likelihood of cancer-related deaths. Nevertheless, there is limited information available regarding the connection between PCDD exposure and the risk of cancer mortality in the general population (i.e., individuals not exposed to these substances through their occupation).MethodsThe National Health and Nutrition Examination Survey (NHANES) detected PCDDs in the general population, and the death data were recently updated as of December 31, 2019. We conducted Cox regression analysis and controlled for covariates including age, gender, ethnicity, educational attainment, physical activity, alcohol intake, NHANES survey period, BMI category, cotinine concentration, and household earnings.ResultsAfter accounting for confounding factors, the findings indicated that for each incremental rise of 1 log unit in 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, there was a 76% rise in the likelihood of death from any cause, with a p value of 0.003. An increase of 1 log unit in the concentration of 1,2,3,4,6,7,8-heptachlorodibenzofuran could potentially lead to a 90% higher risk of cancer mortality, as indicated by a p value of 0.034 and a 95% confidence interval of 0.05–2.43. As the concentrations of 1,2,3,4,6,7,8-heptachlorodibenzofuran increased, the dose–response curve indicated a proportional rise in the risk of cancer mortality, accompanied by a linear p value of 0.044. The sensitivity analysis demonstrated that our findings were resilient.DiscussionIn the general population, an elevated risk of cancer mortality was observed in PCDDs due to the presence of 1,2,3,4,6,7,8-heptachlorodibenzofuran. Mechanistic research is required to further confirm it.
Topic modeling and social network analysis approach to explore diabetes discourse on Twitter in India
Authors: Ramamoorthy Thilagavathi , Kulothungan Vaitheeswaran , Mappillairaju Bagavandas 
Published: February 2024

IntroductionThe utilization of social media presents a promising avenue for the prevention and management of diabetes. To effectively cater to the diabetes-related knowledge, support, and intervention needs of the community, it is imperative to attain a deeper understanding of the extent and content of discussions pertaining to this health issue. This study aims to assess and compare various topic modeling techniques to determine the most effective model for identifying the core themes in diabetes-related tweets, the sources responsible for disseminating this information, the reach of these themes, and the influential individuals within the Twitter community in India.MethodsTwitter messages from India, dated between 7 November 2022 and 28 February 2023, were collected using the Twitter API. The unsupervised machine learning topic models, namely, Latent Dirichlet Allocation (LDA), non-negative matrix factorization (NMF), BERTopic, and Top2Vec, were compared, and the best-performing model was used to identify common diabetes-related topics. Influential users were identified through social network analysis.ResultsThe NMF model outperformed the LDA model, whereas BERTopic performed better than Top2Vec. Diabetes-related conversations revolved around eight topics, namely, promotion, management, drug and personal story, consequences, risk factors and research, raising awareness and providing support, diet, and opinion and lifestyle changes. The influential nodes identified were mainly health professionals and healthcare organizations.DiscussionThe study identified important topics of discussion along with health professionals and healthcare organizations involved in sharing diabetes-related information with the public. Collaborations among influential healthcare organizations, health professionals, and the government can foster awareness and prevent noncommunicable diseases.
Safety evaluation of a buffer used in the lyophilization of canine platelets: type I hypersensitivity reaction in dogs caused by bovine serum albumin
Authors: Choi Hee-Jae , Kim Mu-Young , Han Hyun-Jung 
Published: February 2024

IntroductionThe present study was designed to evaluate the safety of substances generally used in the preparation of lyophilized platelet products (LPPs) because the possibility of an immune response to bovine serum albumin (BSA) was considered high when using previously described technology.MethodsAn intradermal skin test, followed by a drug provocation test, was conducted to observe adverse events and identify the substances responsible for an immune response. Five male beagles (2 years old) weighing 12–14 kg were used. The dogs were clinically healthy and had no history of medication use. An intradermal skin test was conducted with each substance [i.e., 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid, sodium chloride, potassium chloride, sodium bicarbonate, theophylline, trehalose, and BSA] used in the conventional freeze-dry method.ResultsIn the intradermal skin test, three dogs tested positive at the BSA injection site and showed clinical signs after the intradermal injection, including nausea and vomiting. For the drug provocation test, all dogs received two intravenous injections of an LPP buffer solution. The initial injection was devoid of BSA, whereas the subsequent injection contained BSA. The three dogs that had reacted to BSA in the intradermal skin test exhibited adverse events such as lethargy, vomiting, and nausea immediately after intravenous injection of the LPP buffer containing BSA. All dogs recovered uneventfully after symptomatic treatment in both tests.DiscussionThe high incidence and severity of type I hypersensitivity reactions observed in this study suggested that BSA is unsuitable as a component of canine LPP.
HAVANA VELHA, TURISMO INTERNACIONAL E CENTRALIDADES: RUA OBISPO E BOULEVARD SAN RAFAEL
Authors: Pequeno Victor Dantas Siqueira 
Published: February 2024

O presente artigo propõe uma discussão sobre as centralidades urbanas existentes nas cidades contemporâneas e que são decorrentes do investimento de capital para com o setor turístico. Tomo como exemplo a capital cubana que integra a agenda do turismo internacional desde que seu centro histórico foi inserido na lista de Patrimônio Mundial da Humanidade em 1981 pela UNESCO. A partir dos trabalhos de campo realizados entre os meses de setembro a novembro de 2022, foi possível identificar práticas, conteúdos e formas que conferem centralidades à rua Obispo e ao Boulevard San Rafael.
Clinical Outcomes of Scleral Buckling combined with Vitrectomy Pars Plana for Rhegmatogenous Retinal Detachment
Authors: Andry Lukandy  , Sumanti Eugeni 
Published: February 2024

Introduction & ObjectivesThe various types of primary interventions for rhegmatogenous retinal detachment (RRD) includepars plana vitrectomy (PPV), scleral buckling (SB), and combination of both. Intraocular tamponadewith silicone oil (SO) or expanding gas. This research was conducted to evaluate the clinicaloutcomes of SB combined with PPV as a treatment for RRD.
MethodsThis research was prospective descriptive study with total sampling for RRD treated by SB combinedwith PPV from August 2022 to January 2023 in RSUP. Prof. Dr. R.D. Kandou. We observed the BCVA,IOP before and after the surgeries. Clinical findings, intraocular tamponade and complications afterthe surgeries were observed.
ResultsMost of the patients was male with average age of 28 ± 40 years. RRD was observed in 6 eyes andlaterality on right eye. BCVA was 2.5 ± 2 logMAR before the surgery and 2.3 ± 1 logMAR 1 monthafter the surgery. Preoperative IOP was 7 ± 11 mmHg and 13.6 ± 10 mmHg 1 month after thesurgery. Macular detachment, 1 Quadrant Detachment, 1 Number of retina break mostly on superotemporalquadrant were found the most. Proliferative vitreoretinopathy was found in 1 eye.Intraoperative triamcinolone used in 4 eyes and perfluorocarbon in 1 eyes. Subconjunctival bleedingwas found the most, followed by corneal edema and subretinal hemorrhage as postoperativecomplications respectively.
ConclusionThere were several clinical condition seen such as BCVA after the surgery that didn’t improve asexpected, High IOP found in several eyes and subconjunctival bleeding was the complication foundthe most in these eyes.
The Role of Tumor Necrosis Factor (TNF) Alpha with Visual Field Defects in Primary Open Angle Glaucoma (POAG)
Authors: Hutabarat Muhammad Hendy Hasudungan , Sari Masitha Dewi 
Published: February 2024

Introduction & ObjectivesGlaucoma is a group of progressive optic neuropathy disease characterized by degeneration ofretinal ganglion cells. This causes changes in the optic nerve and loss of visual field. Several studieshave revealed that there is a role for TNF Alpha in glaucoma cases. To determine the role TumorNecrosis Factor (TNF) Alpha Levels between visual field defects in Primary Open-angle Glaucomapatients.
MethodsThis study is Observational Analytical with cross sectional data collection method. Examination ofthe field of view using the Humphrey visual field perimetry.
ResultsThe sample of this research was 30 people with 16 (53.3%) male and 14 people (46.7%) female.Using the Spearman correlation test, it showed that there was no significant correlation betweenTNF alpha and field of view (p = 0.119).
ConclusionTNF Alpha level was not significantly related to visual field defects.