bluuebunny/crossref_metadata_2025_split huggingface dataset:
The UPDATE trial (UVB Phototherapy in Dermatology for ATopic Eczema): study protocol for a randomized controlled trial of narrowband UVB with optimal topical therapy versus optimal topical therapy in patients with atopic eczema
Authors: Knöps Eva , Spuls Phyllis , Duijnhoven Ruben , Dijkgraaf Marcel , van Barreveld Marit , Arents Bernd , van Enst Annefloor , Garritsen Floor , Merkus Maruschka , Middelkamp-Hup Maritza Albertina , Musters Annelie , Bosma Angela , Hyseni Ariënna , Dijkstra Jitske , Hijnen Dirk Jan , Gerbens Louise 
Published: July 2024

Abstract

Background
Narrowband ultraviolet B (NB-UVB) phototherapy is commonly prescribed for patients with moderate-to-severe atopic eczema (AE). The efficacy of NB-UVB, however, has not yet properly been established, as current evidence is of low certainty. Our aim is to assess the short-term and long-term (cost-)effectiveness and safety of NB-UVB in adult AE patients by performing a pragmatic, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial. This protocol outlines its methodology.

Methods
A pragmatic, multicenter, PROBE trial will be performed with 1:1 randomization of 316 adult patients with moderate-to-severe AE who have inadequate disease control with topical therapy and who are eligible for optimal topical therapy (OTT) or NB-UVB in combination with OTT as a next step. Participants in the interventional arm will receive a minimum of 3 months of OTT combined with 8 to 16 weeks of NB-UVB. The control group receives 3 months of OTT. Following the interventional phase, follow-up will continue for 9 months. Physician-reported and patient-reported outcomes (according to the Harmonising Outcome Measures for Eczema (HOME) Core Outcome Set) and adverse events are assessed at 4 weeks, 3, 6, 9, and 12 months.

Discussion
The UPDATE trial aims to provide high-quality evidence regarding the (cost-)effectiveness and safety of NB-UVB phototherapy in moderate-to-severe AE patients. Challenges that are addressed in the protocol include the possible bias arising from applying open-label treatment and the necessity of introducing OTT into the study design to prevent a high dropout rate.

Trial registration
ClinicalTrials.gov NCT05704205. Registered on December 8, 2022.
RUNX3-activated apelin signaling inhibits cell proliferation and fibrosis in diabetic nephropathy by regulation of the SIRT1/FOXO pathway
Authors: Zhong Xin , Zhang Jun 
Published: July 2024

Abstract
Background
Diabetic nephropathy is a major secondary cause of end-stage renal disease. Apelin plays an important role in the development of DN. Understanding the exact mechanism of Apelin can help expand the means of treating DN.

Methods
Male C57BL/6 mice was used and STZ treatment was implemented for DN model establishment. Lentivirus systems including Lv-sh-RUNX3 and Lv-Apelin were obtained to knockdown RUNX3 and overexpress Apelin, respectively. A total of 36 mice were divided into 6 groups (n = 6 in each group): control, DN, DN + LV-Vector, DN + Lv-Apelin, DN + LV-Apelin + LV-sh-NC and DN + Lv-Apelin + Lv-sh-RUNX3 group. In vitro studies were performed using mesangial cells. Cell viability and proliferation was assessed through CCK8 and EDU analysis. Hematoxylin and eosin staining as well as Masson staining was implemented for histological evaluation. RT-qPCR was conducted for measuring relative mRNA levels, and protein expression was detected by western blotting. The interaction between SIRT1 and FOXO were verified by co-immunoprecipitations, and relations between RUNX3 and Apelin were demonstrated by dual luciferase report and chromatin immunoprecipitation.

Results
The DN group exhibited significantly lower Apelin expression compared to control (p < 0.05). Apelin overexpression markedly improved blood glucose, renal function indicators, ameliorated renal fibrosis and reduced fibrotic factor expression (p < 0.05) in the DN group, accompanied by elevated sirt1 levels and diminished acetylated FOXO1/FOXO3a (p < 0.05). However, RUNX3 knockdown combined with Apelin overexpression abrogated these beneficial effects, leading to impaired renal function, exacerbated fibrosis, increased fibrotic factor expression and acetylated FOXO1/FOXO3a versus Apelin overexpression alone (p < 0.05). In mesangial cells under high glucose, Apelin overexpression significantly inhibited cell proliferation and fibrotic factor production (p < 0.05). Conversely, RUNX3 interference enhanced cell proliferation and the secretion of fibrotic factors. (p < 0.05). Remarkably, combining Apelin overexpression with RUNX3 interference reversed the proliferation and fibrosis induced by RUNX3 interference (p < 0.05). Mechanistic studies revealed RUNX3 binds to the Apelin promoter, with the 467–489 bp site1 as the primary binding region, and SIRT1 physically interacts with FOXO1 and FOXO3a in mesangial cells.

Conclusion
RUNX3 activated Apelin and regulated the SIRT1/FOXO signaling pathway, resulting in the suppressed cell proliferation and fibrosis in diabetic nephropathy. Apelin is a promising endogenous therapeutic target for anti-renal injury and anti-fibrosis in diabetic nephropathy. RUNX3 may serve as an endogenous intervention target for diseases related to Apelin deficiency.
Unraveling epigenomic signatures and effectiveness of electroconvulsive therapy in treatment-resistant depression patients: a prospective longitudinal study
Authors: Carvalho Silva Rosana , Martini Paolo , Hohoff Christa , Mattevi Stefania , Bortolomasi Marco , Abate Maria , Menesello Valentina , Gennarelli Massimo , Baune Bernhard T. , Minelli Alessandra 
Published: July 2024

Abstract
Background
Electroconvulsive therapy (ECT) benefits patients with treatment-resistant depression (TRD), but the underlying biological processes are unclear. We conducted an epigenome-wide association study in 32 TRD patients undergoing ECT to depict ECT-associated methylation changes. Illness severity and ECT outcomes were assessed with the Montgomery–Åsberg Depression Rating Scale at baseline (T0) and 1 month after its end (T1). Methylation was profiled at T0 and T1 with the Illumina Infinium Methylation EPIC BeadChip array.

Results
Longitudinal T0–T1 analyses showed 3 differentially methylated probes (DMPs) with nominal p values ≤ 10−5, with 2 annotated in the genes CYB5B and PVRL4. Including covariates, we found 4 DMPs for symptoms variation, annotated in FAM20C, EPB41, OTUB1 and ADARB1, and 3 DMPs for response status, with 2 annotated in IQCE and FAM20C. Regional analysis revealed 54 differentially methylated regions (DMRs) with nominal p value area ≤ 0.05, with 9 presenting adjusted p-value area ≤ 0.10, annotated in MCF2L, SLC25A24, RUNX3, MIR637, FOXK2, FAM180B, POU6F1, ALS2CL and CCRL2. Considering covariates, we found 21 DMRs for symptoms variation and 26 DMRs for response (nominal p value area ≤ 0.05), with 4 presenting adjusted p-value area ≤ 0.10 for response, annotated in SNORD34, NLRP6, GALNT2 and SFT2D3. None remained significant after false discovery rate correction. Notably, ADARB1 variants are associated with suicide attempt in patients with psychiatric disorders, and SLC25A24 relates to conduct disorder. Several DMPs and DMRs are annotated in genes associated with inflammatory/immune processes. Longitudinal analyses on females (n = 22) revealed statistically significant DMRs (adjusted p value area ≤ 0.05) and trend-significant DMRs (adjusted p value area ≤ 0.07) for symptoms variation and response status, annotated in genes related to psychiatric disorders (ZFP57, POLD4, TRIM10, GAS7, ADORA2A, TOLLIP), trauma exposure (RIPOR2) and inflammatory/immune responses (LAT, DLX4, POLD4, FAM30A, H19). Pathway analysis on females revealed enrichment for transcriptional activity, growth factors, DNA maintenance, and immune pathways including IRF7 and IRF2.

Conclusion
Although no significant results were found for the whole cohort, the study provides insights into ECT-associated methylation changes, highlighting DMPs and DMRs related to ECT outcomes. Analyses on females revealed significant DMRs and pathways related to psychiatric disorders and inflammatory/immune processes.
Diffuse large B-cell lymphoma in the uterus with unexpected manifestations: a case report
Authors: Tawashi Kenana , Hamasho Tuka , Al-Hussien Mustafa , Ammar Ameen 
Published: July 2024

Abstract
Background
Lymphoid neoplasm is a common disease, arising from lymphoid cells. It is divided into Hodgkin lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be intranodular or extranodular, which happens in 25% of primary cases. The most common locations of extranodular non-Hodgkin lymphoma are the skin and gastrointestinal tract. The genital tract is a rare location; most lymphomas arise from the cervix and vagina, while the uterine corpus is an extremely rare location. In our case, the patient was diagnosed with primary extranodular non-Hodgkin lymphoma in different locations of her genital tract.

Case presentation
A 48-year-old nonparous Syrian woman complained of diffuse abdominal pain, fatigue, debility, high fever, vomiting, and urinary retention for a week. The last menstrual period of the patient was 5 years previously. The physical examination showed periodic abdominal pain with severe fatigue and increased abdominal size. The laboratory investigations were within normal limits except for a low level of hemoglobin and a high level of cancer antigen 125. The radiological investigations showed a uterine sizable lobulated mass with irregular borders and high and heterogeneous density, extending to the right and left ovaries, enlargement lymph nodes around the abdominal aortic and right iliac vessels, and severe right pleural effusion with right inferior lobe atelectasis. A total hysterectomy and oophorectomy were done. The histopathological examination showed that the patient had non-Hodgkin lymphoma (primary tumor).

Conclusion
Primary non-Hodgkin lymphoma in the female genital tract is an extremely rare disease. Fast diagnosis and treatment can improve the outcomes, so this differential diagnosis should be in our minds even in the absence of systematic manifestations of lymphoma. More studies are needed to explain the pathology of this disease and to put guidelines that determine the perfect methods for diagnosis and treatment.
Reliability of the evidence to guide decision-making in the treatment of gastroesophageal reflux disease with acupuncture: protocol for an overview of systematic reviews
Authors: Huang Jinke , Liu Jiali , Wang Fengyun , Tang Xudong 
Published: July 2024

AbstractBackgroundGrowing numbers of randomized clinical trials-based systematic reviews and meta-analyses (SRs/MAs) have been conducted to examine the effectiveness of acupuncture in treating gastroesophageal reflux disease (GERD). An overview of SRs/MAs will be conducted with the aim of systematically compiling, evaluating, and synthesizing the evidence regarding acupuncture for GERD.MethodsSRs/MAs of acupuncture on GERD will be searched in eight databases. Two independent reviewers will conduct the literature search, data extraction, and review quality assessment. Utilizing the AMSTAR-2 tool, PRISMA checklists, and GRADE system, respectively, the methodological quality, reporting quality, and evidence quality will be evaluated. In relation to the subject and the overview’s objects, the results will be given. This study will aid in identifying gaps between evidence and its clinical application and serve as a roadmap for further high-quality research.DiscussionThe results of the overview will aid in closing the gap between clinical evidence and its use in clinical practice. This study will identify significant faults in the use of evidence, point out areas where methodology needs to be improved, and provide guidance for future high-quality research.Systematic review registrationPROSPERO CRD42022371850.Ethics and disseminationEthics approval is not necessary because no personal information about individuals is collected. A peer-reviewed journal or pertinent conferences will publish the results, whichever comes first.
Weight-adjusted-waist index is positively associated with urinary incontinence: results from the National Health and Nutrition Examination Survey (NHANES) 2001–2018
Authors: Cao Shangqi , Hu Xu , Tang Yaxiong , Wu Kang , Yang Weixiao , Li Xiang 
Published: July 2024

Abstract
Background
Urinary incontinence (UI) is closely related to obesity. The aim of this study is to evaluate the association of a novel anthropometric indicator weight-adjusted-waist index (WWI) with UI.

Methods
This cross-sectional study used the data from National Health and Nutrition Examination Survey (NHANES) 2001–2018. Weighted multivariable logistic regression was used to evaluate the relationship between WWI and three types of UI [stress UI (SUI), urgency UI (UUI), and mixed UI (MUI)]. The receiver operating characteristic (ROC) curve and Delong et al.’s test were utilized for comparison of the predictive capability for UI between WWI and body mass index (BMI), waist circumference (WC).

Results
A total of 41,614 participants were included in this study, of whom 23.57% had SUI, 19.24% had UUI, and 9.43% had MUI. In the fully adjusted model, WWI was positively associated with three types of UI [SUI: odds ratio (OR) = 1.19, 95%Confidence interval (CI) 1.13–1.25; UUI: OR = 1.18, 95%CI 1.13–1.24; MUI: OR = 1.19, 95%CI 1.11–1.27, all p < 0.001]. Compared to the lowest WWI interval, the positive correlation between WWI and UI still existed in the highest WWI group after converting WWI to a categorical variable by quartiles (SUI: OR = 1.52, 95%CI 1.35–1.71, p < 0.001; UUI: OR = 1.50, 95%CI 1.33–1.69, p < 0.001; MUI: OR = 1.55, 95%CI 1.32–1.83, p < 0.001). WWI had a stronger prediction for three types of UI than BMI and WC (all p < 0.001).

Conclusion
A higher WWI was linked with an increased likelihood of three types of UI (SUI, UUI, and MUI) in the United State population. Compared to BMI and WC, WWI had a stronger predictive power for UI. WWI may be a better adiposity parameter for evaluating UI.
The involvement of krüppel-like transcription factor 2 in megakaryocytic differentiation induction by phorbol 12-myrestrat 13-acetate
Authors: Wang Zhen , Liu Zhongwen , Zhou Pan , Niu Xiaona , Sun Zhengdao , He Huan , Zhu Zunmin 
Published: July 2024

Abstract
Background
Megakaryocytic differentiation is a complicated process regulated by a series of transcription factors in a context- and stage-dependent manner. Recent studies have suggested that krüppel-like transcription factor 2 (KLF2) is involved in the control of embryonic erythroid precursor cell differentiation and maturation. However, the function and mechanism of KLF2 in regulating megakaryocytic differentiation remain unclear.

Methods
The expression patterns of krüppel-like transcription factors (KLFs) during megakaryocytic differentiation were identified from public databases. Phorbol 12-myristate 13-acetate (PMA) treatment of the myeloid-erythroid-leukemic cell lines K562 and HEL were used as cellular megakaryocytic differentiation models. A lentiviral transduction system was utilized to achieve the goal of amplifying or reducing KLF2. The expression of KLF2 was examined using real-time PCR and western blot. The impact of KLF2 on the megakaryocytic differentiation of K562 cells was examined by flow cytometry, Giemsa staining, Phalloidin staining and western blot. RNA-sequencing (RNA-seq) and chromatin immunoprecipitation-sequencing (ChIP-seq) technologies were used to identify the KLF2-regulated targets.

Results
KLF2 is increased in the maturation process of megakaryocytes. KLF2 overexpression accelerated the PMA-induced megakaryocytic differentiation, as reflected by an increased percentage of CD41/CD61 cells, an increased number of polyploid cells, and an elevated expression of P21 and P27. KLF2 knockdown exhibited the opposite results, indicating that KLF2 knockdown suppressed the megakaryocytic differentiation. Further, combination of the RNA-seq and ChIP-seq results suggested that chimerin 1 (CHN1) and potassium voltage-gated channel subfamily Q member 5 (KCNQ5) may be target genes regulated of KLF2. Both CHN1 and KCNQ5 knockdown could block the megakaryocytic differentiation to some content.

Conclusion
This study implicated a regulatory role of KLF2 in megakaryocytic differentiation, which may suggest KLF2 as a target for illness with abnormal megakaryocytic differentiation.
MonuNet: a high performance deep learning network for Kolkata heritage image classification
Authors: Sasithradevi A. , nathan Sabari , Chanthini B. , Subbulakshmi T. , Prakash P. 
Published: July 2024

Abstract
Kolkata, renowned as the City of Joy, boasts a rich tapestry of cultural heritage spanning centuries. Despite the significance of its architectural marvels, accessing comprehensive visual documentation of Kolkata's heritage sites remains a challenge. In online searches, limited imagery often fails to provide a detailed understanding of these historical landmarks. To address this gap, this paper introduces MonuNet, a high-performance deep-learning network specifically designed for the classification of heritage images from Kolkata. The development of MonuNet addresses the critical need for efficient and accurate identification of Kolkata's architectural marvels, which are significant tangible cultural heritages. The dataset used to train MonuNet is organized by heritage sites, each category within the dataset represents distinct sites. It includes images from 13 prominent heritage sites in Kolkata. For each of these sites, there are 50 images, making it a structured collection where each category (heritage site) is equally represented. The proposed network utilizes a unique architecture incorporating a Dense channel attention module and a Parallel-spatial channel attention module to capture intricate architectural details and spatial relationships within the images. Experimental evaluations demonstrate the superior performance of MonuNet in classifying Kolkata heritage images with an accuracy of 89%, Precision of 87.77%, and Recall of 86.61%. The successful deployment of MonuNet holds significant implications for cultural preservation, tourism enhancement, and urban planning in Kolkata, aligning with the United Nations Sustainable Development Goals (SDGs) for sustainable city development. By providing a robust tool for the automatic identification and classification of heritage images, MonuNet promises to enrich online repositories with detailed visual documentation, thereby enhancing accessibility to Kolkata's cultural heritage for researchers, tourists, and urban planners alike.

Graphical Abstract
A 4-years of radar-based observation of bow echo over Bandung basin Indonesia
Authors: Nugroho Ginaldi Ari , Halimurrahman  , Awaludin Asif , Fathrio Ibnu , Trilaksono Nurjanna Joko , Maryadi Edy , Sinatra Tiin , Renggono Findy , Satiadi Didi , Makmur Erwin , Putra Agie Wandala , Cholianawati Nani , Indrawati Asri , Madethen Tesalonika Angela Putri , Hapsari Ratih Indri 
Published: July 2024

Abstract
Background
This study presents a 4-year (January 2019–April 2023) X-band radar network-based bow echo observation over Great Bandung Indonesia. This study provides insight into the temporal and spatial variability of bow echo distribution and presents the atmospheric condition associated with the bow echo events. Temporal analysis is categorical into monthly, seasonally, and diurnal. The analysis was performed using X-band radar network and reanalysis data (ERA5).

Result
At least 26 bow echoes were identified across the Bandung basin from X-band radar network during the study period. From this total number of bow echoes, the observation of initiation modes is primarily generated from a weakly organized cell, with few coming from the squall line. The bow echo mostly evolved from noon until afternoon. The rainy season (December–January–February) and transition season (March–April–May) is the most frequent period of bow echo occurrence, with March being the most active month. Nevertheless, this study also found bow echo occurrence in the dry season (June–July–August). For the spatial analysis, the studied area is divided into two regions representing the eastern and western part of Bandung basin. The eastern region recorded the most intense occurrences with 14 events. The movement of bow echo in this region covered a shorter distance (average distance only 4.56 km), with all initiation modes occurring inside the region. The atmospheric condition within this region has less moisture flux, with higher CAPE and slightly higher surface temperature. Meanwhile, in the western region have different characteristics with higher moisture flux, a slight effect of CAPE and CINH, with longer distance and zonal movement direction of bow echo displacement.

Conclusion
These conditions indicate that local convection is the dominant mode of bow echo initiation mode in the eastern region of Bandung basin. Meanwhile, the monsoon effect influences the bow echo initiation mode in the western region. Given that the observed 4-year bow echo has different characteristics from previous studies of bow echo in mid latitudes, developing different criteria for bow echo detection in the tropics is crucial.
Mapping of the network connection between sleep quality symptoms, depression, generalized anxiety, and burnout in the general population of Peru and El Salvador
Authors: Yupanqui-Lorenzo Daniel E. , Caycho-Rodríguez Tomás , Baños-Chaparro Jonatan , Arauco-Lozada Tania , Palao-Loayza Luis , Rivera Marlon Elías Lobos , Barrios Iván , Torales Julio 
Published: July 2024

Abstract
Background
A meta-analysis of randomized controlled trials has suggested a bidirectional relationship between sleep problems and mental health issues. Despite these findings, there is limited conclusive evidence on the relationship between sleep quality, depression, anxiety, and burnout.

Objective
The current study aimed to evaluate the relationships between sleep quality symptoms, anxiety, depression, and burnout in samples of adult individuals from two Latin American countries, Peru and El Salvador, through network analysis and to identify key symptoms that reinforce the correlation and intensify the syndromes.

Methods
A total of 1012 individuals from El Salvador and Peru participated, with an average age of 26.5 years (SD = 9.1). Symptom networks were constructed for both countries based on data from the Jenkins Sleep Scale, Patient Health Questionnaire-2, General Anxiety Disorder-2, and a single burnout item.

Results
The results indicated that Depressed Mood, Difficulty Falling Asleep, and Nervousness were the most central symptoms in a network in the participating countries. The strongest conditional associations were found between symptoms belonging to the same construct, which were similar in both countries. Thus, there is a relationship between Nervousness and Uncontrollable Worry, Anhedonia and Depressed Mood, and Nighttime Awakenings and Difficulty in Staying Asleep. It was observed that burnout is a bridge symptom between both countries and presents stronger conditional associations with Tiredness on Awakening, Depressed Mood, and Uncontrollable Worry. Other bridge symptoms include a Depressed Mood and Nervousness. The network structure did not differ between the participants from Peru and El Salvador.

Conclusion
The networks formed by sleep quality, anxiety, depression, and burnout symptoms play a prominent role in the comorbidity of mental health problems among the general populations of Peru and El Salvador. The symptom-based analytical approach highlights the different diagnostic weights of these symptoms. Treatments or interventions should focus on identifying central and bridge symptoms.