bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis
Authors: Nassar Mahmoud , Hassan Ahmed , Ramadan Shrouk , Desouki Mariam Tarek , Hassan Malak A. , Chaudhuri Ajay 
Published: June 2024

Abstract
Background
Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics.

Methods
We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: “Armour Thyroid,” OR “Thyroid extract,” OR “Natural desiccated thyroid,” OR “Nature-Throid,” “desiccated thyroid,” OR “np thyroid,” OR “Synthroid,” OR “levothyroxine,” OR “Liothyronine,” “Cytomel,” OR “Thyroid USP,” OR “Unithroid.” AND “hypothyroidism. “ We only included RCTs and excluded non-RCT, case–control studies, and non-English articles.

Results
From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score.
Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score.

Conclusions
Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended.
Tomographic assessment of bone changes in atrophic maxilla treated by split-crest technique and dental implants with platelet-rich fibrin and NanoBone® versus platelet-rich fibrin alone: Randomized controlled trial
Authors: Anis Maged , Abdelrahman Ahmed Reda , Attia Rasha , Zahran Amr 
Published: June 2024

Abstract
Background
This study evaluated the clinical benefits of adding NanoBone® with split-crest technique and simultaneous implant placement covered with platelet-rich fibrin membrane in horizontally deficient maxillary ridges in terms of crestal and horizontal bone changes and patient morbidity.

Methods
Forty patients indicated for maxillary ridge splitting and simultaneous implant placement were assigned randomly to the study groups: control group (Platelet Rich Fibrin membrane) and test group (Platelet Rich Fibrin membrane + Nanobone®). The Cone Beam Computed Tomography Fusion technique was utilized to assess crestal and horizontal bone changes after five months of the surgical procedure. Patient morbidity was recorded for one week post-surgical.

Results
Five months post-surgical, buccal crestal bone resorption was 1.26 ± 0.58 mm for the control group and 1.14 ± 0.63 mm for the test group. Lingual crestal bone resorption was 1.40 ± 0.66 mm for the control group and 1.47 ± 0.68 mm for the test group. Horizontal bone width gain was 1.46 ± 0.44 mm for the control group and 1.29 ± 0.73 mm for the test group. There was no significant statistical difference between study groups regarding crestal and horizontal bone changes and patient morbidity.

Conclusions
The tomographic assessment of NanoBone® addition in this study resulted in no statistically significant difference between study groups regarding crestal and horizontal bone changes and patient morbidity. More randomized controlled clinical trials on gap fill comparing different bone grafting materials versus no grafting should be conducted.

Clinicaltrials.gov registration number
NCT02836678, 13th January 2017.
Navel orange peel essential oil inhibits the growth and progression of triple negative breast cancer
Authors: Yang Chao , Zhang Wenwen , Xiang Shi , Chen Lai , Chun Jiong , Chen Hui 
Published: June 2024

Abstract
Background
Triple Negative Breast Cancer (TNBC) is a particular type of breast cancer with the highest mortality rate. Essential oils are concerned more and more as potential anti-cancer drugs.

Methods
TNBC cells were treated with different concentrations of navel orange peel essential oil (NOPEO), and then a variety of experiments were performed to investigate the changes in the growth and progression of TNBC cells. MTT assay was performed to detect the proliferation of TNBC cells. The changes of cell cycle and apoptosis were analyzed by FACS. In order to explored the migration of TNBC cells, scratch wound assay was carried out. Western blotting and qPCR were used to examine the expression of proteins and mRNA of related genes. Furthermore, RNA-seq was used to analyze the altered genes and explored the possible signal pathway.

Results
NOPEO demonstrated dose- and time-dependent suppression of TNBC cell growth. TNBC cells showed an increased percentage of G2/M-phase cells and the protein levels of CyclinB1 and CyclinD1 were decreased after NOPEO treatment. The apoptotic cells were increased in the NOPEO treated TNBC cells. The migration mobility was significantly inhibited by NOPEO. In total, 1376 genes were found to be up-regulated and 1335 genes were down-regulated after NOPEO treatment. According to KEGG and GO pathways, the differentially expressed genes were related to MAPK, Jak/stat and FoxQ signaling pathways.

Conclusion
This investigation explored the bio-activity and molecular mechanisms of NOPEO against TNBC cells. These results indicated that NOPEO could suppress TNBC growth and migration perhaps via the MAPK and Jak/stat signaling pathways, which may provide theoretical reference for anticancer drug development. NOPEO may be a potential natural product for the chemotherapeutic of TNBC.
Job satisfaction, professional competence, and self-efficacy: a multicenter cross-sectional study among registered nurses in Sweden and Norway
Authors: Kallerhult Hermansson Stina , Norström Fredrik , Hilli Yvonne , Rennemo Vaag Jonas , Bölenius Karin 
Published: June 2024

Abstract
Background
Healthcare organizations worldwide face persistent challenges relating to turnover and intention to leave the nursing profession among registered nurses. Factors contributing to their retention and well-being at work include high job satisfaction, professional competence, and self-efficacy. Few multicenter studies have investigated these factors in relation to work experience in a Nordic context. Therefore, this study aimed to investigate job satisfaction, professional competence, and self-efficacy among registered nurses.

Methods
This multicenter cross-sectional study survey was part of a larger overarching Swedish-Norwegian project, and was conducted among registered nurses (n = 1137) in September 2021. The participants worked in a variety of health care units, e.g., hospital units, primary health care, and home care. Data was subjected to descriptive and comparative statistical analysis; chi-square test, one-way between-groups analysis of variance (ANOVA) and Kruskal-Wallis test.

Results
The findings show that job satisfaction is reported as lowest in registered nurses with medium-term work experience as compared to newly qualified and long-term work-experienced registered nurses. Professional competence and self-efficacy are reported as higher among registered nurses with long-term work experience as compared to those with medium-term work experience and newly qualified registered nurses. However, the participants reported their professional competence as highest in relation to the same factor – “Value-based nursing care” – regardless of their work experience.

Conclusions and implications
This study underscores the need for continuous support and professional development for registered nurses throughout their careers. Proactive support for newly qualified nurses may improve job satisfaction as they progress to being registered nurses with medium-term work experience. Tailored interventions to address the distinct needs of both newly qualified and medium-term work-experienced registered nurses are crucial for nurturing a sustainable nursing workforce.
Access to civil justice as a social determinant of health: a legal epidemiological cross-sectional study
Authors: Fung Eddy Hin Chung , Dong Dong 
Published: June 2024

Abstract
Background
Although it is widely acknowledged that access to civil justice (ATJ) is a key social determinant of health (SDOH), the existing literature lacks empirical evidence supporting ATJ as a SDOH for specific dimensions of health.

Methods
A legal epidemiological, cross-sectional, postal survey was conducted on n = 908 randomly sampled participants in Hong Kong in March 2023. Data collected were perceptions of the civil justice system, health, and sociodemographics. Perceived ATJ was assessed using a modified version of the Inaccessibility of Justice scale (IOJ) and Perceived Inequality of Justice scale (PIJ), i.e. the “modified IOJ-PIJ”, consisting of 12 of the original 13 items from both scales divided into two subdomains: “procedural fairness”, and “outcome neutrality”. For health data, quality of life was assessed using the Hong Kong version of the Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-BREF(HK)), psychological distress (including symptoms of anxiety and depression) was assessed using the four-Item Patient Health Questionnaire (PHQ-4), and having comorbidities was assessed using Sangha’s Self-Administered Comorbidity Questionnaire (SCQ). Structural equation modelling (SEM) was used to investigate the relationships between perceived ATJ and the measured health outcomes.

Results
SEM demonstrated that both subdomains for ATJ had significantly negative associations (B < 0; p < 0.05) with all quality-of-life subdomains, except for between outcome neutrality with social relationships; both subdomains for ATJ had significantly positive association (B > 0; p < 0.05) with both anxiety and depression; and, after adjusting for age, only “procedural fairness” had significantly positive association (B > 0; p < 0.05) with having comorbidities.

Conclusion
This study provided empirical evidence that ATJ is a SDOH for specific dimensions of health. The results of this study encourage laws, policies, and initiatives aimed at improving ATJ, as well as collaborative efforts from the legal and health sectors through health-justice partnerships, and from the broader community, to safeguard and promote public health by strengthening ATJ.
Mapping of spastic muscle activity after stroke: difference between passive stretch and active contraction
Authors: Xie Tian , Leng Yan , Xu Pan , Li Le , Song Rong 
Published: June 2024

Abstract
Background
Investigating the spatial distribution of muscle activity would facilitate understanding the underlying mechanism of spasticity. The purpose of this study is to investigate the characteristics of spastic muscles during passive stretch and active contraction by high-density surface electromyography (HD-sEMG).

Methods
Fourteen spastic hemiparetic subjects and ten healthy subjects were recruited. The biceps brachii (BB) muscle activity of each subject was recorded by HD-sEMG during passive stretch at four stretch velocities (10, 60, 120, 180˚/s) and active contraction at three submaximal contraction levels (20, 50, 80%MVC). The intensity and spatial distribution of the BB activity were compared by the means of two-way analysis of variance, independent sample t-test, and paired sample t-test.

Results
Compared with healthy subjects, spastic hemiparetic subjects showed significantly higher intensity with velocity-dependent heterogeneous activation during passive stretch and more lateral and proximal activation distribution during active contraction. In addition, spastic hemiparetic subjects displayed almost non-overlapping activation areas during passive stretch and active contraction. The activation distribution of passive stretch was more distal when compared with the active contraction.

Conclusions
These alterations of the BB activity could be the consequence of deficits in the descending central control after stroke. The complementary spatial distribution of spastic BB activity reflected their opposite motor units (MUs) recruitment patterns between passive stretch and active contraction. This HD-sEMG study provides new neurophysiological evidence for the spatial relationship of spastic BB activity between passive stretch and active contraction, advancing our knowledge on the mechanism of spasticity.

Trial registration
ChiCTR2000032245.
Evaluation of novel Epstein-Barr virus-derived antigen formulations for monitoring virus-specific T cells in pediatric patients with infectious mononucleosis
Authors: Fischer Franziska , Mücke Johannes , Werny Louisa , Gerrer Katrin , Mihatsch Lorenz , Zehetmaier Stefanie , Riedel Isa , Geisperger Jonas , Bodenhausen Maren , Schulte-Hillen Lina , Hoffmann Dieter , Protzer Ulrike , Mautner Josef , Behrends Uta , Bauer Tanja , Körber Nina 
Published: June 2024

Abstract
Background
Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM).

Methods
We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset).

Results
All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (rs = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells.

Conclusions
All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.
Versatile DNA extraction from diverse plant taxa using ionic liquids and magnetic ionic liquids: a methodological breakthrough for enhanced sample utility
Authors: De Silva Shashini , Cagliero Cecilia , Gostel Morgan R. , Johnson Gabriel , Anderson Jared L. 
Published: June 2024

Abstract
Background
There is a growing demand for fast and reliable plant biomolecular analyses. DNA extraction is the major bottleneck in plant nucleic acid-based applications especially due to the complexity of tissues in different plant species. Conventional methods for plant cell lysis and DNA extraction typically require extensive sample preparation processes and large quantities of sample and chemicals, elevated temperatures, and multiple sample transfer steps which pose challenges for high throughput applications.

Results
In a prior investigation, an ionic liquid (IL)-based modified vortex-assisted matrix solid phase dispersion approach was developed using the model plant, Arabidopsis thaliana (L.) Heynh. Building upon this foundational study, the present study established a simple, rapid and efficient protocol for DNA extraction from milligram fragments of plant tissue representing a diverse range of taxa from the plant Tree of Life including 13 dicots and 4 monocots. Notably, the approach was successful in extracting DNA from a century old herbarium sample. The isolated DNA was of sufficient quality and quantity for sensitive molecular analyses such as qPCR. Two plant DNA barcoding markers, the plastid rbcL and nuclear ribosomal internal transcribed spacer (nrITS) regions were selected for DNA amplification and Sanger sequencing was conducted on PCR products of a representative dicot and monocot species. Successful qPCR amplification of the extracted DNA up to 3 weeks demonstrated that the DNA extracted using this approach remains stable at room temperature for an extended time period prior to downstream analysis.

Conclusions
The method presented here is a rapid and simple approach enabling cell lysis and DNA extraction from 1.5 mg of plant tissue across a broad range of plant taxa. Additional purification prior to DNA amplification is not required due to the compatibility of the extraction solvents with qPCR. The method has tremendous potential for applications in plant biology that require DNA, including barcoding methods for agriculture, conservation, ecology, evolution, and forensics.
Novel developments in the study of estrogen in the pathogenesis and therapeutic intervention of lymphangioleiomyomatosis
Authors: Tai Jingye , Liu Shihua , Yan Xinping , Huang Luantai , Pan Yingxin , Huang Hongyuan , Zhao Zhen , Xu Beini , Liu Jie 
Published: June 2024

Abstract
Objective
This study aimed to enhance the understanding of the role of estrogen in lymphangioleiomyomatosis(LAM) and to conclude the impact of estrogen-altering events on the condition and recent advances in estrogen-based treatments for LAM.

Results
LAM development is strongly linked to mutations in the tuberous sclerosis gene (TSC1/2) and the presence of estrogen. Estrogen plays a significant role in the spread of TSC2-deficient uterine leiomyoma cells to the lungs and the production of pulmonary LAM. Menstruation, pregnancy, estrogen medication, and other events that cause an increase in estrogen levels can trigger the disorder, leading to a sudden worsening of symptoms. Current findings do not support using estrogen-blocking therapy regimens. However, Faslodex, which is an estrogen receptor antagonist, presents new possibilities for future therapeutic approaches in LAM.

Conclusion
Estrogen is crucial in the development and spread of LAM. The use of estrogen inhibitors or estrogen receptor antagonists alone does not provide good control of the disease or even poses a greater risk, and the use of a combination of mTOR receptor inhibitors, complete estrogen receptor antagonists, estrogen inhibitors, and autophagy inhibitors targeting important signaling pathways in LAM pathogenesis may be of greater benefit to the patient.
Gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT): a clinicopathological analysis of four rare cases
Authors: Zhou Ping , Fu Yiyun , Wang Weiya , Tang Yuan , Jiang Lili 
Published: June 2024

Abstract
Background
SMARCA4, as one of the subunits of the SWI/SNF chromatin remodeling complex, drives SMARCA4-deficient tumors. Gastric SMARCA4-deficient tumors may include gastric SMARCA4-deficient carcinoma and gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Gastric SMARCA4-UT is rare and challenging to diagnose in clinical practice. The present report aims to provide insight into the clinicopathological characteristics and genetic alterations of gastric SMARCA4-UTs.

Results
We retrospectively reported four rare cases of gastric SMARCA4-UTs. All four cases were male, aged between 61 and 82 years. These tumors presented as ulcerated and transmural masses with infiltration, staged as TNM IV in cases 1, 2 and 4, and TNM IIIA in case 3. Pathologically, four cases presented solid architecture with undifferentiated morphology. Cases 2 and 3 showed focal necrosis and focal rhabdoid morphology. Immunohistochemical staining showed negative expression of epithelial markers and deficient expression of SMARCA4. Furthermore, positivity for Syn (cases 1, 2 and 3) and SALL4 (cases 1 and 2) were observed. Mutant p53 expression occurred in four cases, resulting in strong and diffuse staining of p53 expression in cases 1, 2 and 4, and complete loss in case 3. The Ki67 proliferative index exceeded 80%. 25% (1/4, case 4) of cases had mismatch repair deficiency (dMMR). Two available cases (cases 1 and 3) were detected with SMRACA4 gene alterations. The response to neoadjuvant therapy was ineffective in case 1.

Conclusions
Gastric SMARCA4-UT is a rare entity of gastric cancer with a poor prognosis, predominantly occurs in male patients. The tumors are typically diagnosed at advanced stages and shows a solid architecture with undifferentiated morphology. Negative expression of epithelial markers and complete loss of SMARCA4 immunoexpression are emerging as a useful diagnostic tool for rare gastric SMARCA4-UTs.