bluuebunny/crossref_metadata_2025 huggingface dataset:
BATF-Activated AIM2 Mediates Immune Escape in Lung Adenocarcinoma by Regulating PD-L1
Authors: Liu Xiang , Zhou Wangyan , Zheng Dayang , Yang Xu , Qing Yongcheng , Liao Weijun , Zeng Wei
Published: October 2024

Introduction: Immunotherapy has demonstrated encouraging outcomes in tackling lung adenocarcinoma (LUAD), but immune escape may bring negative impacts. Only a single study has demonstrated the function of AIM2 in LUAD and reported that NF-κB and STAT1 are the chief transcription factors, this study is designed to analyze the role of AIM2 and examine the transcription factor, BATF in LUAD immunotherapy. Methods: Bioinformatics methods to analyze the expression and binding sites of AIM2 and BATF in LUAD, as well as the correlation between AIM2 and PD-L1. Dual-luciferase and chromatin immunoprecipitation assays were used to verify the binding of AIM2 and BATF. qRT-PCR and Western blot assayed expression of AIM2, BATF, and PD-L1 in LUAD. MTT measured cell viability, flow cytometry detected cell apoptosis, cytotoxicity assays measured the toxicity of CD8+ T cells to cancer cells, and enzyme-linked immunosorbent assay measured the expression of related cytokines. Immunohistochemistry detected the protein expression levels of AIM2, BATF, PD-L1, and CD8 in tumor tissue. Results: AIM2 and BATF were both highly expressed in LUAD, and there was a targeted binding relationship. BATF promoted LUAD cell proliferation and inhibited apoptosis by affecting AIM2 expression. The downregulation of AIM2 and PD-L1 expression inhibited PD-L1 and activated CD8+ T cells. The rescue experiment manifested that increased BATF weakened repression of AIM2 silencing on LUAD tumor immune escape in vitro and in vivo. Conclusion: BATF promoted AIM2 expression, upregulated PD-L1, inhibited CD8+ T cell activity, and ultimately led to immune escape in LUAD. Our research uncovered an innovative outlook on the intricate regulation of immune checkpoint molecules and proposed a new approach to target the BATF/AIM2 axis in tumor immunotherapy.
Effectiveness of Intranasal Corticosteroids for Sleep Disturbances in Patients with Allergic Rhinitis: A Systematic Review and Meta-Analysis
Authors: Tabata Kenshiro , Sumi Yukiyoshi , Sasaki Hatoko , Kojimahara Noriko
Published: October 2024

Introduction: Allergic rhinitis (AR) is a chronic condition caused by an immunoglobulin E-mediated response to environmental allergens, which affects 10–40% of the global population. AR symptoms, such as nasal congestion and rhinorrhea, significantly reduce quality of life and are associated with sleep disturbances, further exacerbating the condition’s burden. Despite the known impact of AR on sleep, the effects of intranasal corticosteroids on sleep quality have not been comprehensively reviewed. Therefore, this systematic review and meta-analysis aimed to investigate the efficacy of intranasal corticosteroids in improving sleep quality among patients with AR. Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study protocol was registered with PROSPERO (CRD42023460698). A comprehensive search was conducted on PubMed, Cochrane Central Register of Controlled Trials, and Ichushi-Web. Randomized controlled trials (RCTs) comparing intranasal corticosteroids with placebos in patients with AR were included. Data extraction and risk of bias assessment were independently performed by two authors. The primary outcome was the improvement in sleep quality measured by standardized questionnaires. Meta-analyses were performed using a random-effects model. The risk of bias was assessed using the RoB2 tool. Results: Eighteen RCTs involving 6,019 participants were included. The meta-analysis of 12 comparisons from eight studies for the Rhinoconjunctivitis Quality of Life Questionnaire sleep domain showed significant improvement in sleep quality with a standardized mean difference (SMD) of 0.292 (95% confidence interval [CI]: 0.235–0.350, p < 0.0001, I2 = 0.0%). The Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire also showed improvement with an SMD of 0.284 (95% CI: 0.164–0.404, p < 0.0001) based on two comparisons from one study. However, the Epworth Sleepiness Scale did not show significant results (SMD: 0.027, 95% CI: −0.429 to 0.483, p = 0.907) based on two comparisons from two studies. Sensitivity analysis, excluding two studies with high risk of bias according to RoB2, confirmed the robustness of these results. Subgroup analyses for patients with seasonal or perennial AR showed significant improvements in both groups. Conclusion: This study demonstrates that intranasal corticosteroids significantly improve sleep quality in patients with AR. These findings support the use of intranasal corticosteroids as a first-line treatment for AR, not only for managing daytime symptoms but also for enhancing sleep quality. Future research should focus on sleep quality changes as a primary outcome and incorporate both subjective and objective measures to better understand the relationship between sleep and AR symptoms.
Reoperation Rates and Risk Factors after Spinal Cord Stimulation Revision Surgery
Authors: Kim Samuel H. , Lopez Ramos Christian G. , Palan Mihir J. , Kronquist Elise , Tan Hao , Elkholy Mohamed Amgad Elsayed , Raslan Ahmed
Published: October 2024

Introduction: Spinal cord stimulation (SCS) is an effective treatment for patients with refractory chronic pain. Despite its efficacy, rates of reoperation after initial implantation of SCS remain high. While revision rates after index SCS surgeries are well reported, less is known about rates and risk factors associated with repeat reoperations. We sought to evaluate patient, clinical, and surgical characteristics associated with repeat reoperation among patients who underwent an initial SCS revision procedure. Methods: We performed a retrospective review of patients who underwent SCS revision surgery performed at a single institution between 2008 and 2022. Patients were stratified by whether they underwent a single revision (SR) or multiple revision (MR) surgeries. Multivariate logistic regression was performed to determine risk factors associated with repeat SCS revision. Kaplan-Meier survival analysis was used to compare rates of devices requiring revision across groups. Results: A total of 54 patients underwent an initial SCS revision. Of these, 15 (28%) underwent a second revision. The most common indication for revision surgery was lead migration (65%). No significant differences were observed in age, body mass index, comorbidities, lead type, and revision indication among the SR and MR groups. On multivariate adjusted analysis, only cervical lead position was significantly associated with repeat reoperation (OR 7.10, 95% CI [1.14, 44.3], p = 0.036). Time to reoperation after a single and MR SCS surgeries did not differ. Conclusions: Among patients who undergo SCS reoperation, a substantial portion requires additional revisions. Cervical lead placement may be associated with a higher risk of repeat revision surgery compared to thoracic lead positioning. Consideration of lead positioning in the decision to perform and undergo reoperation may therefore result in lower revision rates and improved clinical outcomes among SCS patients with MRs.
Analyzing the Role of Specific Damage-Associated Molecular Patterns-Related Genes in Osteoarthritis and Investigating the Association between β-Amyloid and Apolipoprotein E Isoforms
Authors: Yuan Fangling , Tang Yatian , Zheng Feifei , Xie Qipeng
Published: October 2024

Introduction: Osteoarthritis (OA) is a prevalent chronic joint disorder. It is characterized by an immune response that maintains a low level of inflammation throughout its progression. During OA, cartilage degradation leads to the release of damage-associated molecular patterns (DAMPs), which intensify the inflammatory response. β-Amyloid is a well-recognized DAMP in OA, can interact with APOE isoforms. Methods: This study identified DAMPs-related genes in OA using bioinformatics techniques. Additionally, we examined the expression levels of β-amyloid and apolipoprotein E (ApoE) isoforms by enzyme-linked immunosorbent assay. Results: We identified 10 key genes by machine learning techniques. Immune infiltration analysis revealed upregulation of various immune cell types in OA cartilage, underscoring the critical role of inflammation in OA pathogenesis. In the validation study, elevated serum levels of β-amyloid in knee osteoarthritis (KOA) patients were confirmed, showing positive correlations with ApoE2 and ApoE4. Notably, ApoE3 was identified as an independent protective factor against KOA. Conclusion: In this bioinformatics analysis, we identified the DAMPs-related genes of KOA and explored their potential functions and regulatory networks. The high expression of β-amyloid in KOA was confirmed by experiments, and the correlation between β-amyloid and ApoE2, ApoE4 in KOA was revealed for the first time, this provides a new way to explore the pathogenesis of KOA and to study the therapeutic targets of KOA.
Colorectal Endoscopic Full-Thickness Resection: A Portuguese Multicenter Experience Based on a Retrospective Cohort
Authors: Mendes Raquel R. , Mascarenhas André , Correia João , Estevinho Maria Manuela , Pereira Rodrigues Jaime , Conceição Daniel , Saraiva Sofia , Mão De Ferro Susana , Nascimento Catarina Neto , Loureiro Rui , Costa Mara Sarmento , Gravito-Soares Elisa , Chaves Jéssica , Libânio Diogo , Dinis Ribeiro Mário , Archer Sara , Küttner Magalhães Ricardo , Bronze Sérgio , Noronha Ferreira Carlos , Tarrio Isabel , Araújo Tarcísio , Barreiro Pedro
Published: October 2024

Introduction: Endoscopic full-thickness resection (EFTR) is a minimally invasive endoscopic technique that allows the resection of complex colorectal lesions, such as non-lifting, peri-appendicular, peri-diverticula, and subepithelial lesions. Published data suggest that EFTR has a technical success and R0 resection rates of 89 and 79%, respectively, and an adverse event rate of 12%. This study summarizes the EFTR experience in nine Portuguese centers with regard to its efficacy and safety. Methods: This was a multicenter uncontrolled retrospective study, including 129 colorectal EFTRs between March 2017 and September 2023. The main outcomes were procedural and technical success, R0 resection, curative resection, adverse events, and recurrence rate. Results: 129 EFTR procedures were conducted, with a technical success rate of 88.4% (114/129). Most lesions were in the right colon, with a median resection size of 25 [10–45] mm. R0 and curative resection rates were 75.9% (85/112) and 58.0% (65/112), respectively. Adverse events occurred in 13.2% (17/129) of patients, mostly due to immediate perforation, appendicitis, or delayed bleeding, needing surgery in 5.4% (7/129). Local recurrence occurred in 5.4% (5/92) of resections. Conclusion: This real-life multicenter study highlights the utility of colorectal EFTR for management of complex and carefully chosen lesions, with an acceptable adverse events rate and need for surgery.
Transgender Legal Recognition in North Africa: Between the Hammer of Sharia and the Anvil of the Judiciary
Authors: Noralla Nora
Published: October 2024

The right to legal gender recognition is integral to transgender rights and is the final step for many transgender people to realise their true gender identity. However, In North Africa, this right is primarily restricted due to the lack of a legislative framework that governs the issue. This legislative vacuum means two things: firstly, principles of Sharīʿah are the de-facto law regulating the matter, and secondly, Courts will have the jurisdiction over reviewing legal gender recognition applications. Sunni Islamic scholars did engage on transgender issues starting in the 1980s when Egypt’s Al-Azhar and Saudi Arabia’s Islamic Fiqh Council issued prominent fatwas, providing a very unfavourable interpretation of transgender people. The fatwas viewed transgender people as mentally ill who should not be allowed access to gender-affirming healthcare and should be provided with mental treatment to ‘return to their true sex’ and fit within the binary. While the fatwas only discussed banning access to gender-affirming healthcare, North African Courts adapted this ban to mean a ban on legal gender recognition for transgender people. Thus, judicial opinions in the region developed to deny legal gender recognition on the grounds of Sharīʿah. However, a 2018 Tunisian Court became an anomaly when it reinterpreted Sharīʿah to allow a transman legal gender recognition in a landmark decision. The impact of this judgment remains limited, as so far, Courts still maintain their ban on legal gender recognition. The paper is conducting the primary scholarly effort to establish a legal theory on legal gender recognition for transgender people in North Africa by investigating the issue by analysing case law from Egypt, Tunisia, Algeria, and Sunni Fatwas from Al-Azhar and Islāmic Fiqh Council to theorise the region’s legal and religious discourse on legal gender recognition for transgender people.
Ottoman Tobacco and the Moral Economy of State-Led Development (c. 1908–12)
Authors: Adney Kaleb Herman
Published: October 2024

In the Second Constitutional Era (1908–18), proponents of various models for national development debated the Ottoman future under the Committee for Union and Progress (cup). Public discussions of cup policies related to the tobacco sector were central to these discussions in the southern Balkans. As such, they provide a window into the political and moral economy of the region and some of the public critiques of international finance after the 1908 Constitutional Revolution. By 1908, tobacco had been at the crossroads of regional economic development and European financial domination for nearly three decades. Since the domestic tobacco monopoly was set to expire in 1913, the region was primed for debates about the agricultural credit market and the customs regime. This article argues that cup proposals for state-led development aimed to satisfy the divergent moral demands of agriculturalists (zürrāʿ) and merchants (tüccar) in the tobacco-producing zones of the empire.
Dielectric drying of black soldier fly larvae (Hermetia illucens): impact on microbiological product quality, safety and stability
Authors: Vandeweyer D. , Lachi D. , Geheniau H. , Goovaerts V. , van der Zweep P. , Groffils C. , Thijs M. , Van Der Borght M.
Published: October 2024

Along with the increasing scale of industrial production of insects as food and feed, the need for processing methods applicable on large scale is rising within the insect sector. One important processing technology in this context is drying, which aims at stabilising the quality of the insects. This study investigated the impact of dielectric drying technologies, specifically microwave (μW) and radio frequency (RF) drying, on the microbiological quality, safety, and stability of black soldier fly (BSF) larvae in comparison to the traditional methods oven drying and freeze drying. Before, during and after subjecting a large batch of blanched BSF larvae to the four drying technologies, their water activity and moisture content as well as general microbial and pathogen counts were assessed. Dielectric drying effectively reduced water activity, thus enhancing product stability. Microbiological analyses revealed the efficacy of blanching in microbial reduction, with dielectric (especially RF) drying further contributing to these reductions. The results, however, do not conclusively support nonthermal microbial inactivation through dielectric treatment. Specific analyses targeting foodborne pathogens indicated the absence of most selected bacterial pathogens, except for (presumptive) Bacillus cereus. This pathogen was detected in a few samples but remained below safety thresholds and was effectively eliminated by dielectric drying. Finally, a shelf life stability evaluation showed minimal changes in dielectrically dried BSF larvae over six months, indicating a microbiologically stable product. In conclusion, dielectric drying technologies can retain or even improve the microbiological quality and stability of BSF larvae in the insect industry and can be considered as valuable and more efficient (time, energy consumption) alternatives to oven and freeze drying.
The Analogate of the Divine Physician in the Clinic: Understanding the Christian Health Care Professional as a Symbol of Christ
Authors: Swindeman Joseph Peter
Published: October 2024

The Divine Physician is a traditional title that the Church gives to Jesus Christ. This metaphor helps symbolize Jesus's mission to heal our souls of sin and its effects. In this paper, I consider this metaphor as a source for understanding the vocation of the Catholic physician. Understanding that the role of the laity is to communicate the divine law to the world, I argue that this title raises the human physician's dignity to the status of an image of Christ's saving activity in the clinic. This paper roots this dignity in the supernatural life of grace by giving both a philosophical and a theological exposition of the metaphor of the Divine Physician.
Historical Control Background Incidence of Spontaneous Nonneoplastic Lesions of Sprague Dawley Rats in 104-Week Carcinogenicity Studies
Authors: Bockenstedt Marie , Kumar Amit , Laast Victoria , Sharma Alok
Published: October 2024

Microscopic observation data collected from approximately 1800 male and female Sprague Dawley (SD) control rats used on 104-week carcinogenicity studies performed at North American Labcorp Early Development, Inc, Madison, WI, were retrospectively evaluated for spontaneous nonneoplastic findings. This study provides incidence of the most common spontaneous nonneoplastic microscopic findings in each organ system of SD rats encountered during 104-week carcinogenicity studies. Some of the most common spontaneous background findings were cardiomyopathy; chronic progressive nephropathy; uterine cystic endometrial hyperplasia; prostate inflammation; pulmonary alveolar macrophage infiltrates; hepatocyte vacuolation, bile duct hyperplasia, and basophilic foci in the liver; pancreatic fibrosis; splenic extramedullary hematopoiesis and pigment; decreased lymphocytes and epithelial hyperplasia in the thymus; ventral brain compression; cystic degeneration and hyperplasia of the adrenal cortex; and mammary gland hyperplasia. The most common nonneoplastic findings in male SD rats were chronic progressive nephropathy (80.9%) and rodent progressive cardiomyopathy (73.2%). The most common nonnenoplastic findings in female SD rats were cystic degeneration of the adrenal cortex (64.7%) and ventral compression of the brain due to pituitary neoplasms (62.7%).
Wrist Stabilising Exercise Versus Hand Orthotic Intervention for Persons with Hypermobility – A Randomised Clinical Trial
Authors: Susanne Lindholm , Lisbeth Claesson
Published: October 2024

Objective

To investigate the effectiveness of wrist stabilisation exercises compared to conventional intervention, whether it reduces pain and/or paraesthesia in the hand, as well as how the interventions affected activity ability, health-related quality of life and effects on hand function and grip strength in people with Hypermobility Diagnosis.

Design

A randomised controlled trial. Setting: Units of Occupational therapy in Primary Care, Kalmar County Council, Sweden Participants: The study included 169 participants’ data randomised to the Exercise group (n = 83) or the Control group (n = 86). The samples consisted of adults in diagnosed Hypermobility Spectrum Disorders or hypermobility Ehlers Danlos Syndrome with symptoms of pain and/or paraesthesia in the hands in the last three years. Interventions: The Exercise group trained according to structured progressive exercises and weights programme. The Control group used the hand orthosis during selected activities. Both groups performed randomised intervention for 12 weeks. Main measures: The primary outcome was the Disabilities of Arm, Shoulder, and Hand questionnaire. Secondary outcomes were the Grip Ability Test, the Jamar dynamometer and the EuroQol EQ-5D.

Results

There were 116 subjects who completed the intervention. There were no statistically significant difference between the wrist stabilisation exercise and the conventional intervention in terms of activity ability, health-related quality of life, hand function, grip strength, pain or paraesthesia in people with Hypermobility Spectrum Disorders or hypermobility Ehlers Danlos Syndrome.

Conclusion

There is no statistically significant difference between the Exercise group and the Control group regarding activity ability after 12 weeks intervention period.
Trust in leader and positive employee outcomes: To transform or to serve in cross-cultural leadership
Authors: Nazarian Alireza , Rodríguez Molina Miguel A , Velayati Rezvan , Ruiz-Alba José L , Atkinson Peter
Published: October 2024

Considering the potential impacts of context-specific value systems in individuals’ perceptions of phenomena, this study seeks to investigate whether and how cultural differences could influence the effectiveness of leadership styles in establishing trust and positive employee outcomes (PEOs) as well as the relationships between such outcomes based on the GLOBE project. The sample consisted of 1647 valid responses from 128 independent hotels’ employees in four countries from two GLOBE clusters (Anglo and South Asia). Multilevel structural equation modelling has been used for the analysis. Significant but different relationships were found between Servant Leadership and Transformational Leadership with Trust, and PEOs in the two clusters, which could be potentially attributed to societal and contextual factors as a deeper layer mechanism. Our findings have significant implications for both academics and hotel managers in terms of the critical role of alignment between context-specific contingencies and the selected leadership style in establishing trust and PEOs.
The Impact of Judicial Selection Method on State Supreme Court Justice Ideology
Authors: Waterbury Nicholas W. , Simmons Alan J.
Published: October 2024

Among political institutions in the United States, state courts are surprisingly susceptible to ideological extremism because of the non-uniform ways judges are selected. In this paper we examine the effect of selection methods on the ideological composition of state supreme courts. We theorize that methods involving partisan politics lead to more ideological justices and that, among that subset, Republican affiliated justices will be the most extreme. We test our expectations using a dataset of over 600 state supreme court selections between 1961–2011. Using a contemporary matching algorithm designed to maximize causal identification, we find support for our hypotheses. Our results speak to the consequences of federalism in court composition and offer an insight into how polarization manifests in the judiciary.
Mobile robot navigation based on intrinsic reward mechanism with TD3 algorithm
Authors: Yang Jianan , Liu Yu , Zhang Jie , Guan Yong , Shao Zhenzhou
Published: October 2024

Deep reinforcement learning methods have been applied to mobile robot navigation to find the optimal path to the target. The rewards are usually given when the task is completed, which may lead to the local optima during the training procedure. It seriously affects the training efficiency and navigation performance of the mobile robot. To this end, this paper proposes an intrinsic reward mechanism with intrinsic curiosity module and randomness enhanced module, combining the TD3 (twin-delayed deep deterministic policy gradient) reinforcement learning algorithm for mobile robot navigation. It effectively resolves the issue of slow convergence caused by sparse rewards in continuous action spaces. It also encourages mobile robots to explore unknown areas and reduces the occurrence of local optima. The experimental results show that the proposed navigation method significantly improves the training efficiency of mobile robots. Out of 1000 test episodes, only 3 exceeded the maximum step limit. This approach significantly reduces the occurrence of local optima. Furthermore, it increases the success rate to an impressive 83.5%, outperforms the existing navigation methods.
Exploring the Challenges Faced by Primary Care Physicians in Providing Optimal Care for Patients With Hypertension: A Qualitative Study
Authors: Oka Prawira , Moosa Aminath Shiwaza , Ng Chirk Jenn
Published: October 2024

Background:

Globally, most patients with hypertension have suboptimal blood pressure (BP) control. Multiple barriers prevent primary care physicians (PCPs) from effectively caring for these patients. This study aimed to explore the challenges faced by PCPs in providing optimal care for patients with hypertension, with a specific focus on identifying new barriers.

Methods:

This qualitative study involved 17 PCPs across 5 primary care clinics in Singapore. A trained researcher conducted individual in-depth interviews using a topic guide. Purposive sampling was employed to ensure adequate representation of seniority until data saturation was achieved. The audio-recorded interviews were transcribed verbatim and independently checked. The data were managed using NVivo and thematic analysis was conducted.

Results:

New barriers were divided into patient, physician, drug, and systemrelated factors. Patient factors included a preference for natural health remedies and the inconvenience of blood tests. Meanwhile, physicians faced challenges diagnosing and treating patients with various BP phenotypes and BP variability. The initiation of dual therapy was a drugrelated barrier. Finally, system factors included the suboptimal layout of the electronic medical records (EMR) that impeded effective hypertension management.

Conclusion:

A multi-pronged approach is required to address the significant barriers to providing optimal hypertension care. Patients should be empowered through education and minimizing the inconvenience of medication titrations. Additionally, physicians should be better equipped to diagnose and treat patients with more challenging BP phenotypes. Finally, improved access to combination pills and an optimized EMR would contribute to improved care for patients with hypertension.
‘Discursive Interpretations of Cultural Symbols in Mega Sporting Events: The Case of Messi’s Bisht at the 2022 World Cup’
Authors: Ghobain Elham
Published: October 2024

This study examines the dominant narratives and media frames surrounding the moment when football celebrity Lionel Messi wore a bisht during the World Cup 2022 crowning ceremony. Employing a frame analysis approach, the research seeks to uncover the discursive meanings tied to this moment, which is heightened by national identity and nationalism in the context of globalized sport across international media platforms. A corpus of 25, 208 words from 59 online news articles was analyzed. At a macro level, the articles were largely framed within themes of conflict, controversy, criticism, and public and media reactions. The findings, which include specific cultural, national, political, economic, and identity frames, offer valuable insights into the complexities of globalization, nationalism, and cosmopolitanism in mega sporting events. Through discursive interpretations, this study provides a nuanced understanding of cultural exchange and identity issues in the globalized world of sports. Global media portrayed Messi’s bisht moment both positively (as a symbol of honor and respect) and negatively (as an instance of identity exploitation for cultural publicity). The study also reveals that Qatar was perceived as leveraging the event for national branding. Notably, nationalism and ideologies emerge as critical factors in media framing of mega sporting events.
Dihydroberberine alleviates Th17/Treg imbalance in premature ovarian insufficiency mice via inhibiting Rheb/mTOR signaling
Authors: Deng Disi , Wu Yeke , Wu Keming , Zeng Nan , Li Wanjing
Published: October 2024

Background

Premature ovarian insufficiency (POI) is an immune-related condition. Dihydroberberine (dhBBR) plays a regulatory role in maintaining the T-helper 17 (Th17)/regulatory T (Treg) cell balance. This study aimed to explore the action mechanisms of dhBBR on POI.

Methods

In vivo, female BALB/c mice were used as POI models, treated with dhBBR, or injected with recombinant interleukin (rIL)-17 and anti-CD25 monoclonal antibody. Hematoxylin and eosin staining was used to validate the model and assess the therapeutic effects of dhBBR. mRNA expression levels of cytochrome P450 (Cyp)-17a1, Cyp19a1, Cyp11a1, steroidogenic acute regulatory protein, and luteinizing hormone receptor in mouse ovaries were quantified via quantitative polymerase chain reaction (qPCR). Enzyme-linked immunosorbent assay was used to determine the cytokine and sex hormone levels. Immunohistochemical staining for cleaved-caspase 3 and Ki-67 were performed to assess ovarian cell apoptosis and proliferation. Flow cytometry was used to analyze the Th17/Treg cell balance in the ovary and spleen. In vitro cytotoxicity of dhBBR was measured using the cell counting kit-8 assay. GTP-Ras homolog enriched in brain (Rheb) activity was determined via immunofluorescence assay. Co-immunoprecipitation was performed to assess Rheb activity, Th17 or Treg induction, and binding between Rheb and mammalian target of rapamycin (mTOR) after dhBBR treatment. Flow cytometry and qPCR assays were used to verify the effect of dhBBR on CD4 + cell differentiation. Finally, Rheb/mTOR pathway activation was confirmed via western blotting of proteins, including mTOR, p-mTOR, p70S6K, p-p70S6K, 4E-BP1, and p-4E-BP1.

Results

dhBBR improved the ovarian function in a dose-dependent manner. It also decreased ovarian cell apoptosis and increased cell proliferation. It decreased Th1 and Th17 cell proportions but increased Treg cell proportions in the ovaries and spleens of POI model mice. Cell experiments revealed that dhBBR promoted CD4 + cell differentiation into Treg cells. Co-immunoprecipitation revealed Rheb as the dhBBR target that bound to mTOR. However, MHY1485 restored dhBBR-induced changes in forkhead box P3, IL-10, transforming growth factor-β1, IL-17, IL-22, retinoic acid-related orphan receptor-γt and p-mTOR levels in Th17- and Treg-induced CD4 + cells.

Conclusion

Overall, dhBBR targeted the Rheb/mTOR pathway to promote CD4 + cell differentiation into Treg cells and alleviate POI.
Antineoplastic with DNA fragmentation assay and anti-oxidant, anti-inflammatory with gene expression activity of Lactobacillus plantarum isolated from local Egyptian milk products
Authors: Elhalik Mohamed A. , Mekky Alsayed E. , Khedr Mohamed , Suleiman Waleed B.
Published: October 2024

Many lactic acid bacteria (LAB), known for their human health benefits, are derived from milk and utilized in biotherapeutic applications or for producing valuable nutraceuticals. However, the specific role of milk-associated LAB in biotherapeutics remains underexplored. To address this, eight milk product samples were randomly selected from the Egyptian market, diluted, and then cultured anaerobically on MRS agar. Subsequently, 16 suspected LAB isolates were recovered and underwent rapid preliminary identification. Among these isolates, the Lactobacillus plantarum strain with accession number (OQ547261.1) was identified due to its strong antioxidant activity depending on the DPPH assay, L. plantarum displayed notable antioxidant activities of 71.8% and 93.8% at concentrations of 125–1000 µg/mL, respectively. While ascorbic acid showed lower concentrations of 7.81, 3.9, and 1.95 µg/mL which showed activities of 45.1%, 34.2%, and 27.2%, respectively. The anti-inflammatory efficacy of L. plantarum was evaluated based on its capability to prevent hemolysis induced by hypotonic conditions. At a concentration of 1000 µg/mL, L. plantarum could reduce hemolysis by 97.7%, nearly matching the 99.5% inhibition rate achieved by the standard drug, indomethacin, at an identical concentration. Moreover, L. plantarum exhibited high hemolytic activity at 100 µg/mL (14.3%), which decreased to 1.4% at 1000 µg/mL. The abundance of phenolic acids and flavonoids was determined by high-performance liquid chromatography (HPLC) in L. plantarum. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) demonstrated that L. plantarum increased gene expression of the inflammatory marker TLR2 by 133%, and cellular oxidation markers SOD1 and SOD2 by 65% and 74.2%, respectively, while suppressing CRP expression by 33.3%. These results underscore L. plantarum’s exceptional anti-inflammatory and antioxidant activities. Furthermore, L. plantarum induces cancer cell death through necrotic nuclear DNA fragmentation. These findings suggest that L. plantarum is not only suitable for nutraceutical production but also holds potential as a probiotic strain. Future research should focus on enhancing the capacity of this strain across various industries and fostering innovation in multiple fields.
The tale of two Ions Na+ and Cl−: unraveling onion plant responses to varying salt treatments
Authors: Romo-Pérez M. L. , Weinert C. H. , Egert B. , Kulling S. E. , Zörb C.
Published: October 2024

Background

Exploring the adaptive responses of onions (Allium cepa L.) to salinity reveals a critical challenge for this salt-sensitive crop. While previous studies have concentrated on the effects of sodium (Na+), this research highlights the substantial yet less-explored impact of chloride (Cl−) accumulation. Two onion varieties were subjected to treatments with different sodium and chloride containing salts to observe early metabolic responses without causing toxicity.

Results

The initial effects of salinity on onions showed increased concentrations of both ions, with Cl− having a more pronounced impact on metabolic profiles than Na+. Onions initially adapt to salinity by first altering their organic acid concentrations, which are critical for essential functions such as energy production and stress response. The landrace Birnförmige exhibited more effective regulation of its Na+/K+ balance and a milder response to Cl− compared to the hybrid Hytech. Metabolic alterations were analyzed using advanced techniques, revealing specific responses in leaves and bulbs to Cl− accumulation, with significant changes observed in organic acids involved in the TCA cycle, such as fumaric acid, and succinic acid, in both varieties. Additionally, there was a variety-specific increase in ethanolamine in Birnförmige and lysine in Hytech in response to Cl− accumulation.

Conclusion

This comprehensive study offers new insights into onion ion regulation and stress adaptation during the initial stages of salinity exposure, emphasizing the importance of considering both Na+ and Cl− when assessing plant responses to salinity.
CYP2C19 loss-of-function variants are independent risk factors for premature cerebral infarction: a hospital based retrospective study
Authors: Shi Yuliang , Yang Yuxian , Feng Miaoling , Wu Heming
Published: October 2024

Objective

Cytochrome P450 2C19 (CYP2C19) plays an vital role in the course of cardiovascular and cerebrovascular diseases by affecting lipid metabolism. Triglyceride-glucose (TyG) is a comprehensive index composed of triglyceride and blood glucose, has relationship with some diseases. There was no research report on the association CYP2C19 polymorphisms, TyG with premature cerebral infarction (CI) (onset ≤ 65 years old) susceptibility.

Methods

This study retrospectively analyzed 1953 CI patients aged ≤ 65 years old from December 2018 to March 2024, and 1919 age-matched individuals with non-CI as controls. The relationship between CYP2C19 polymorphisms, TyG and premature CI risk were analyzed.

Results

The proportion of hypertension, and diabetes mellitus in patients with premature CI was higher than those in controls. The serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and TyG levels in patients with premature CI were significantly higher than those in controls (all p < 0.05). The patients had lower CYP2C19 *1 allele frequency (63.3% vs. 69.6%, p < 0.001) and higher CYP2C19 *2 allele frequency (31.3% vs. 25.4%, p < 0.001) than controls. Logistic regression analysis showed that smoking history (odds ratio (OR): 1.193, 95% confidence interval (CI): 1.002–1.422, p = 0.048), hypertension (OR: 3.371, 95% CI: 2.914–3.898, p < 0.001), diabetes mellitus (OR: 1.911, 95% CI: 1.632–2.237, p < 0.001), CYP2C19 intermediate metabolizer (IM) + poor metabolizer (PM) phenotypes (OR: 1.424, 95% CI: 1.243–1.631, p < 0.001), and dyslipidemia (OR: 1.294, 95% CI: 1.077–1.554, p = 0.006) were independent risk factors for premature CI.

Conclusions

History of smoking, hypertension, diabetes mellitus, dyslipidemia, and CYP2C19 IM + PM phenotypes were independently associated with premature CI susceptibility.
Survival risk stratification based on prognosis nomogram to identify patients with esophageal squamous cell carcinoma who may benefit from postoperative adjuvant therapy
Authors: Zhang Yumeng , Xu Weilin , Wu Mengxing , Li Yurong , Chen Guanhua , Cheng Yu , Sun Xinchen , Yang Liang , Zhou Shu
Published: October 2024

Objective

The purpose of the study is to develop a prognosis nomogram for esophageal squamous cell carcinoma (ESCC) patients with radical resection and to identify patients who may benefit from postoperative adjuvant radiotherapy/chemoradiotherapy through survival risk stratification.

Methods

We retrospectively enrolled patients who underwent esophagectomy in the First Affiliated Hospital of Nanjing Medical University from July 2015 to June 2017. Patients with stage I-III esophageal squamous cell carcinoma who received radical R0 resection with or without postoperative adjuvant radiotherapy/chemoradiotherapy were included. Further, patients were randomly allocated into two groups (training and validation cohorts) with a distribution ratio of 7:3. The prognosis nomogram was constructed based on independent factors determined by univariate and multivariate Cox analyses. The area under the receiver operating characteristic curve (AUC) and calibration curve were adopted to evaluate the discriminative ability and reliability of the nomogram. The accuracy and clinical practicability were respectively assessed by C-index values and decision curve analysis (DCA), and further contrasted the nomogram model and the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system. In addition, survival risk stratification was further performed according to the nomogram, and the effect of postoperative adjuvant therapy on each risk group was appraised by the Kaplan-Meier survival analysis.

Results

A total of 399 patients with esophageal squamous cell carcinoma were recruited in this study, including the training cohort (n = 280) and the validation cohort (n = 119). The nomogram-related AUC values ​​for 1, 3, and 5-year OS were 0.900, 0.795, and 0.802, respectively, and 0.800, 0.865, 0.829 in the validation cohort, respectively. The slope of the calibration curve for both cohorts was close to 1, indicating good consistency. The C-index value of the nomogram was 0.769, which was higher than that of the AJCC 8th TNM staging system by 0.061 (p < 0.001). Based on the prognosis nomogram, patients were stratified into three risk groups (low, medium, and high), and there were obvious differences in prognosis among the groups (p < 0.001). Furthermore, postoperative adjuvant therapy has been shown to enhance the 5-year survival rate by over 15% among patients classified as medium- and high-risk.

Conclusion

The constructed nomogram as developed resulted in accurate and effective prediction performance in survival outcomes for patients with stage I-III esophageal squamous cell carcinoma who underwent radical R0 resection, which is superior to the AJCC 8th TNM staging system. The survival risk stratification had potential clinical application to guide further personalized adjuvant therapy.
Digitalising the past decades: automated ICD-10 coding of unstructured free text dermatological diagnoses
Authors: Sitaru Sebastian , Nhan Fabian , Gasteiger Christine , Rueckert Daniel , Biedermann Tilo , Zink Alexander
Published: October 2024

Background

Current digital medical databases record systematically coded diagnoses, but many legacy databases are full of hand-written, free text diagnoses, which can only be meaningfully analysed after mapping them to a coding system. While diagnoses can be extracted from full medical notes with good accuracy, no algorithm using only an unstructured free text diagnosis with no additional data has been published to date.

Objectives/methods

Therefore, we sought to create an algorithm which maps hand-written German diagnoses from our clinical photography database to ICD-10 diagnosis codes, validate its output manually by dermatologists and analyse diagnosis counts over time as a proof-of-concept of its application.

Results

Our rule-based algorithm mapped 50,884 unprocessed hand-written German free-text diagnoses covering five decades to ICD-10 codes, while reaching an accuracy of 82% against 817 dermatologist-validated diagnoses. Out of 41,021 data points with the highest algorithm confidence the top 3 identified diagnosis classes were psoriasis, eczema, and non-melanoma skin cancer. The number of ICD-10 codes belonging to chronic inflammatory diseases showed a seasonal pattern with peaks in July, and when analysed aggregated by year, peaks correlated to events such as new therapy classes for these diseases.

Conclusion

Using the presented algorithm, it is possible to reliably match hand-written free text of German dermatological diagnoses to ICD-10 codes, thus enabling systematic analysis of legacy databases, making past medical knowledge accessible to today’s patient care.
Breastfeeding in patients with peripartum cardiomyopathy: clinical outcomes and physician counseling
Authors: Noll Angelina , Kawamoto Kris R. , Dassanayake Maya T. , Leuenberger Laura , Spehar Stephanie M. , Wu Jenny , Langen Elizabeth , Davis Melinda B.
Published: October 2024

Background

Peripartum cardiomyopathy (PPCM) is a form of heart failure occurring towards the end of pregnancy or in the months following delivery. Concerns regarding the role of prolactin (the polypeptide hormone responsible for lactation) driving the pathogenesis of PPCM have led experts to discourage patients from breastfeeding; however, limited clinical data exist. We sought to (1) determine whether lactation was associated with less cardiac recovery and (2) assess the counseling about breastfeeding given to patients at the time of their initial diagnosis.

Methods

Patients diagnosed with PPCM from 1999 to 2019 were identified through detailed chart review and demographic characteristics, comorbidities, outcomes, and lactation status were collected. Cardiac recovery was defined as left ventricular ejection fraction (LVEF) 55% or higher. A survey about breastfeeding and patient experience was administered by mail. Patients were only included in this analysis if definitive information about lactation status was documented.

Results

Of 220 patients with confirmed PPCM, lactation status was known definitively in 54 patients; of these, 18 (33%) had breastfed for at least 6 weeks and 36 (67%) did not breastfeed. There were no significant differences in the breastfeeding and non-breastfeeding groups related to baseline LVEF, age, race, gestational diabetes, smoking, hypertensive disorders of pregnancy, and medication treatments. Despite similar baseline LVEF at the time of diagnosis, there was no statistically significant difference in cardiac recovery based on lactation status. In a subset of patients with severe cardiac dysfunction at the time of diagnosis, there remained no significant differences in recovery based on lactation status. Of the 34 survey respondents, 62% were told not to breastfeed due to their diagnosis or concerns regarding safety of medications, and none were encouraged to breastfeed.

Conclusion

In this retrospective cohort, lactation was not associated with lower rates of myocardial recovery. Importantly, a majority of patients had received counseling that they should not breastfeed. Future studies of the role of lactation in PPCM are needed in order to better understand the impact of breastfeeding and improve patient counseling.
Effect of hip abductors training on pelvic drop and knee valgus in runners with medial tibial stress syndrome: a randomized controlled trial
Authors: Lashien Shreen Ahmed , Abdelnaeem Ahmed Omar , Gomaa Ebtessam Fawzy
Published: October 2024

Background

Medial tibial stress syndrome (MTSS) is a prevalent running-related injury that could impact athletic performance and quality of life. The purpose of the study was to investigate the effectiveness of functional hip abductor strength training on reducing contralateral pelvic drop angle (hip frontal plane projection angle), and dynamic knee valgus (knee frontal plane projection angle) in runners with medial tibial stress syndrome (MTSS).

Methods

Forty male and female recreational runners were diagnosed with MTSS for at least one month. The age ranged from 25 to 35 years old, and the body mass index (BMI) ranged between (18.5 and 25 kg/m2) participated in this study. This was a single-blind, randomized controlled trial. Participants were randomized into two groups: a control group (Group A, n = 20) received a selected physical therapy exercise program, and an experimental group (Group B, n = 20) received the same program plus functional hip abductor strength training. Dynamic knee valgus (frontal plane projection angle) and contralateral pelvic drop angle were measured using 2D video and analyzed by Kinovea software at baseline and after 8 weeks. Mixed-effect multifactor analysis of variance (MANOVA) was conducted to compare within and between groups effects on FPPA and pelvic drop angle.

Results

After 8 weeks, Group B exhibited a significantly decreased frontal plane projection and pelvic drop angles compared to Group A (p < 0.05). Group A also demonstrated a reduced pelvic drop angle, but to a lesser extent, and their frontal plane projection angle increased.

Conclusions

This study demonstrates that 8 weeks of functional hip abductor strength training, combined with traditional physical therapy, effectively improves lower extremity kinematics in runners with MTSS by reducing dynamic knee valgus and contralateral pelvic drop. This targeted approach likely addresses underlying muscle weakness and movement dysfunction, offering hope for potentially reducing MTSS recurrence.

Trial registration: clinicaltrials.gov. NO: NCT05637476. Date: December 1, 2022.