bluuebunny/crossref_metadata_2025_split huggingface dataset:
M2-like Macrophages-derived CCL17 Promotes Esophageal Squamous Cell Carcinoma Metastasis and Stemness via Activating CCR4-mediated ERK/PD-L1 Pathway
Authors: Jin Chun , Lu Liangliang , Gao Jian , Chen Ling 
Published: October 2024

Background and objective:
High morbidity, high mortality and poor
prognosis of esophageal squamous cell carcinoma (ESCC) highlights the urgent need
for novel therapeutic strategies against ESCC. The current study addresses the
precise role of M2-like macrophages-derived CCL17 in ESCC progression and to
thoroughly elucidate the intrinsic molecular mechanisms.

Methods:
In this work, for functional experiments, Eca109 cells cultivated in M2-CM
were treated with anti-IgG (50 μg/ml) or anti-CCL17 (50 μg/ml) to expound the tumorpromoting
effects of M2-like macrophage-derived CCL17 in ESCC. Moreover, for
rescue experiments, Eca109 cells were treated with CCL17 (50 ng/ml) and/or CCR4
antagonist AZD2098 (20 μM) to probe whether CCL17 could influence the malignant
behaviors including migration, invasion and stemness of ESCC cells via activating
CCR4/ERK/PD-L1 pathway.

Results:
Markedly enhanced CCL17 secretion was observed in M2-like macrophages.
CCL17 bound to CCR4 to activate ERK/PD-L1 signaling. M2-like macrophagesderived
CCL17 facilitated ESCC cell migration and invasion and enhanced stemness
characteristics of ESCC cells, which were partially reserved by AZD2098 treatment.
The tumor-promoting effects of M2-like macrophages-derived CCL17 on ECSS was
depended on the activation of CCR4/ERK/PD-L1 pathway.

Conclusion:
To conclude, M2-like macrophages-derived CCL17 could facilitate ESCC
cell migration and invasion and enhance stemness characteristics of ESCC cells via
activating CCR4/ERK/PD-L1 signaling.
Identification of Key miRNAs in Endometriosis
Authors: Blandino Francesca , Barbati Saviana Antonella , Forlani Luca , Coppola Giulia , Meschino Noemi , Cecchinelli Ilde , Mazzuca Antonietta Cosco , Veltri Valentina , Giannico Riccardo , Calugi Graziella 
Published: October 2024

Introduction:
Endometriosis, a prevalent gynecological disorder characterized by the
presence of endometrial-like tissue outside the uterus, poses significant challenges in diagnosis
and management due to its unclear pathogenesis and lack of specific biomarkers.

Objective:
This study investigates the potential use of microRNAs (miRNAs) as key markers in
endometriosis by studying two cohorts of patients (14 patients diagnosed with endometriosis and
15 patients with gynecological benign lesions, different from endometriosis).

Methods:
MicroRNA sequencing analysis was tested within data management by a custom pipeline
designed by Eurofins Genoma Group.

Results:
We identified a specific miRNA expression profile associated with endometriosis to
feature specific disease molecular clusters to further elucidate the underlying mechanisms driving
endometriosis pathogenesis.
Data from the present study suggest a specific miRNA scar for endometriosis compared to other
gynecological diseases to develop screening tools in early diagnosis and to ameliorate the management
of the disease itself.

Conclusion:
This study lays the foundation for the identification of key miRNAs involved in the
disease pathogenesis to unveil the molecular signatures in the complex scenario of endometriosis.
Further validation and exploration of these findings are needed to develop tools to improve molecular
diagnosis and to create a machine-learning prediction algorithm in the future.
An Evidence-Based Comprehensive Review of Laughter Therapy in Depression Management
Authors: Pannu Arzoo , Goyal Ramesh K. , Kumari Parina 
Published: October 2024

Abstract:
Depression is a widespread mental health challenge, necessitating diverse
therapeutic approaches. Emerging research suggests that laughter may offer
a valuable adjunctive intervention for individuals grappling with depressive
symptoms. This review systematically investigates the multifaceted relationship
between laughter and depression, elucidating the underlying mechanisms and potential
therapeutic benefits. A comprehensive literature search was conducted
across multiple electronic databases, including PubMed, PsycINFO, Scopus,
and Google Scholar. Keywords used in the search included “laughter therapy,”
“humor,” “depression,” “mental health,” and “psychological well-being.” The
search was limited to articles published in English and included both peer-reviewed
journal articles and relevant gray literature. Relevant data were extracted
from each study, including the study design, sample size, participant characteristics,
type of laughter intervention, duration and frequency of the intervention,
outcome measures, and key findings. The extracted data were organized into tables
to facilitate comparison across studies. By synthesizing findings from clinical
studies, neuroscience research, and anecdotal evidence, this review examines
the physiological, psychological, and social dimensions of laughter's impact on
depression. Special attention is given to neurochemical pathways, stress modulation,
cognitive restructuring, and social dynamics. The physiological effects of
laughter on depression encompass neurochemical regulation (endorphins, serotonin,
dopamine), stress reduction, and immune system modulation. Psychologically,
laughter contributes to cognitive reframing, enhanced coping mechanisms,
and mood regulation. Socially, it strengthens social bonds, mitigates social
isolation, and fosters a positive social environment. In conclusion, this review
synthesizes current knowledge on the healing potential of laughter in mitigating
depression, providing a holistic understanding of its multifaceted impact.
The findings underscore the importance of integrating laughter-based interventions
into mental health care practices and highlight avenues for future research
and clinical applications in the realm of depression treatment.
Bedaquiline Delivery Innovations: A Review on Advancing MDR-TB Treatment Strategies
Authors: Ahmad Asad , Akhtar Juber , Ahmad Mohammad , Badruddeen  , Khan Mohammad Irfan , Singh Aditya , Islam Anas 
Published: October 2024

Abstract:
Multidrug-resistant tuberculosis (MDR-TB) poses a persistent challenge to
global health, necessitating continuous efforts to enhance treatment efficacy. Bedaquiline,
a cornerstone in MDR-TB management, presents biopharmaceutical challenges that impact
its therapeutic potential. This review provides a comprehensive analysis of recent innovations
in drug delivery strategies designed to optimize Bedaquiline's efficacy and improve
MDR-TB treatment outcomes. Through a systematic examination of various delivery systems,
including nanotechnology and formulation advancements, we explore their potential
in addressing drug solubility and bioavailability challenges. Emphasizing the integration of
Quality by Design (QbD) principles, this review aims to present a cohesive overview of
evolving Bedaquiline delivery innovations, providing valuable insights for researchers and
healthcare practitioners working towards advancing MDR-TB treatment strategies.
Home Transcutaneous Electrical Stimulation Rehabilitation Program for Patients With Ankylosing Spondylitis: Crossover Trial
Authors: Lin Yu-Chih , Wu Chen-Ching , Sung Wan-Yu , Yen Jeng-Hsien , Lin Yi-Ching 
Published: October 2024

Background
Maintaining physical function and preserving spinal flexibility have been challenging in managing ankylosing spondylitis (AS). Most rehabilitation programs, including manual therapy, massage, hydrotherapy, and acupuncture, cannot be performed at home. The effect of transcutaneous electrical nerve stimulation (TENS) was validated in treating AS, but no home TENS system has explored its efficacy to date.

Objective
This study aims to evaluate the efficacy of a home TENS system with a novel treatment program for patients with AS.

Methods
The modified WeHeal TS-200 TENS and galvanic response system provided home-based TENS treatment for patients with AS. Patients were divided into a 2-month course group and a 1-month course group. After the first treatment course, patients went through a washout period for the same duration of their treatment course. Participants could decide whether to accept the second course of treatment. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Schober test, finger-to-floor flexion test, enthesis score, cytokines, chemokines, inflammatory factors, and immunoglobulins were measured to evaluate its efficacy. The clinical trial protocol (1096607481) received approval from the Ministry of Health and Welfare in Taiwan.

Results
A total of 9 patients (5 in a 2-month course group and 4 in a 1-month course group) completed the first treatment course, and 5 patients (4 in a 2-month course group and 1 in a 1-month course group) completed the sequential treatment course. The weighted results showed that patients reported an improving BASFI score (mean difference –0.9, SD 1.7; P=.03) after treatment. Looking into the trajectories, declined BASFI and BASDAI scores were noticed during treatments; this score increased during the washout period. There were improving trends in the Schober test (mean difference 1.9, SD 4.9; P=.11) and finger-to-floor flexion test (mean difference –0.6, SD 9.5; P=.79), but the results were not statistically significant. The response of cytokines, chemokines, inflammatory factors, and immunoglobulins before and after treatment did not show a consistent trend, and all results were not statistically significant (all P>.05).

Conclusions
The home TENS device demonstrated a potential role in AS management. It may improve accessibility and adherence for patients with AS and provide remote monitoring for clinicians. Further research can compare the effectiveness of electrotherapy at home or in a medical setting and focus on integrating the home TENS system and exercise program to enhance patients’ physical functions and spinal flexibility.
Themes in Abortion Forum Discussions in a Restrictive Access Context: Qualitative and Quantitative Analyses
Authors: Klimiuk Krzysztof Bartosz , Kot Amelia , Majcherek Ewa , Kubiak Katarzyna B , Balwicki Łukasz 
Published: October 2024

Background
Abortion is one of the most common medical procedures worldwide. Despite this, access to abortion on demand remains restricted in many countries, including Poland. As a result, many women resort to undergoing the procedure without medical supervision, putting themselves at risk of serious health consequences such as drug poisoning, excessive bleeding, and hypovolemia. Unfortunately, some abortions also lead to severe infections.

Objective
This study aims to qualitatively identify key themes in abortion forums to analyze the issues faced by individuals. The forums were then quantitatively analyzed to determine which problems were most prevalent.

Methods
The most popular abortion forums were identified. A preliminary thematic analysis was conducted for the qualitative phase, followed by a manual quantitative analysis. Two independent researchers reviewed forum posts, categorizing them into specific themes.

Results
An analysis of 13,397 responses from 370 threads across 4 forums revealed “Abortion Process Progression” as the most discussed theme, highlighting a strong demand for information, emotional support, and medical guidance. The highest percentage of threads (162/886, 18.3%) focused on the need for mental support and the desire to have someone in contact during the abortion process. Concerns about the effectiveness of the termination also emerged as a significant topic, accounting for 83 of the 886 (9.4%) discussions. “Emotional and Psychological Aspects” and “Medical and Pharmacological Aspects” were also significant, highlighting the need for holistic care. Anxiety and fear related to the process were frequently discussed, accounting for 60 of the 886 (6.8%) responses. The issue of isolation and lack of support was also a common topic, appearing in 30 of the 886 (3.4%) threads. Notably, “Social and Ethical Perception” accounted for only 13 of the 886 (1.5%) responses and appeared in just 13 threads.

Conclusions
This study highlights the critical need for information and support for women navigating abortion, particularly in regions where access is restricted. It emphasizes the importance of addressing the multifaceted challenges women face and calls for policy changes and strengthened support networks to improve the health and rights of women, as well as all those seeking gynecological care in abortion contexts. Further research is encouraged to refine and expand support strategies.
Research on the Current Status and Countermeasures of Family Education Guidance Provided by Kindergartens in the Transition from Kindergarten to Primary School: A Case Study of X Kindergarten in Jimo District, Qingdao City, Shandong Province
Authors: Zhao Mengyao , Yan Jingru 
Published: October 2024

This study investigates the current status of family education guidance provided by kindergartens during the transition from kindergarten to primary school in Jimo District, Qingdao City, Shandong Province, and proposes recommendations and strategies for improvement. The research identifies several issues, including deficiencies in the organizational management of family education guidance by kindergartens and the lack of a robust regulatory framework. To address these challenges, kindergartens should establish a constructive mutual assistance mechanism for family education during the transition from kindergarten to primary school and enhance teachers' empathetic skills. Additionally, a collaborative effort between home and kindergarten is essential to ensure a smooth transition for both parents and children into the primary school stage.
Disciplinary Liability and Other Means Impacting the Employee’s Behaviour in Labour Relations in Latvia and Lithuania
Authors: Kārkliņa Annija , Mačernytė-Panomariovienė Ingrida 
Published: October 2024

The article examines the regulation and practice of employee liability in employment relationships in two Baltic states – Latvia and Lithuania. Considering that the Latvian Labour Law regulates the disciplinary liability of employees, while in Lithuania disciplinary punishments (except for the most severe punishment – dismissal) have not been provided for since 2017, the authors analyse the regulatory framework of these countries and reflect on the case law, as well as outline the main differences and problematic issues in the context of employee liability.
Direct Recall as an Instrument of Political Liability of Public Authorities Before Voters in the Republics of Poland and Latvia
Authors: Jackiewicz Andrzej , Rytel-Warzocha Anna 
Published: October 2024

The direct and participatory democracy is becoming increasingly popular in recent years in Europe. States are introducing new institutions into their constitutional systems, which, on the one hand, strengthen the ability of citizens to influence decision-making processes and, on the other hand, allow them to control the actions of public authorities. One of such institutions is a “recall”, which provides citizens with the right to recall, by way of voting, the public authorities elected directly by citizens. The institution of recall may take either direct or indirect form. Nevertheless, only a “direct recall” that takes place at the request of citizens can fully satisfy their interests. The direct recall at the national level is a relatively rare institution, hence, Latvian solutions in this area that allow for the recall of parliament before the end of its term may be considered unique, whilst in Poland the institution of direct recall occurs at the local level. Polish experiences with the practice of recalls indicate that for this institution to function effectively, it is necessary to adopt appropriate legal regulations. For example, the high turnout threshold adopted in both countries, which determines the binding nature of the vote, may be a factor that significantly reduces the effectiveness of this measure. The authors present the current legal regulations concerning the institution of direct recall in both states, as well as provide their critical assessment.
Domestic Violence in the Focus of Estonian Penal Policy and Implementation of the Law in the Light of the Istanbul Convention Requirements
Authors: Kaugia Silvia 
Published: October 2024

Domestic violence is a multi-faceted phenomenon, encompassing social, psychological, medical and, certainly, legal aspects. Depending on the existing legal framework, it is the lawyers who have the possibility and even the duty to assist and protect the victim and to apply various sanctions against the perpetrator. The decision on the Principles of Criminal Policy until 2030, adopted by the Estonian Parliament, formulates the goal of the penal system as supporting law-abiding lifestyles and thus ensuring that the norms based on the values of our society are implemented, violations are responded to and conflicts are resolved fairly. These are goals that, if realised, could also contribute to reducing domestic violence in society. Estonia has ratified the Istanbul Convention and has made amendments to national legislation in accordance with the requirements of the Convention. Dealing with cases of domestic violence is nevertheless relatively problematic, especially from the perspective of the victim. The predominance of the settlement procedure or the practice of out-of-court restorative justice and conciliation in domestic violence cases, in the opinion of this author, tends to support the position of the perpetrator of violence.
Towards Greater Freedom of Expression for Judges. The Rejection of a Culture of Judicial Silence and Its Benefits for Liberal Democracy*
Authors: Wojtanowski Mateusz 
Published: October 2024

The current study asserts that the rejection of a culture of judicial silence is beneficial to the architecture of liberal democracy, as judicial expression outside a courtroom assists in maintaining a balance between its components. On the one hand, this can create defence mechanisms against the alienation of the law from society (which appropriately appreciates the democratic component), while on the other, it aids in the actualization of the constitutionally determined role of the judiciary within the political system (safeguarding the liberal element). The discussion, which is essentially based on an analysis of international soft law, commences by examining two areas pertaining to judicial expression outside a courtroom: public discussion on the law and generally understood social life involvement. Subsequently, the limits of judges’ expression during such activities are analysed, and three proposals for their definition are put forward. As a next step, the paper highlights the diversity of judges as relevant to the problem at hand. The work concludes by outlining its findings, which also include the potential risks associated with the proposed project.
State Aid to Electricity Producers: National and EU Law Aspects
Authors: Rodiņa Anita , Ūdre Dārta 
Published: October 2024

At European Union level, there is a detailed regulatory framework allowing Member States to introduce state aid. State aid is always granted for a specific purpose and helps Member States to achieve their common objectives. The energy sector is being moved towards reaching targets for both energy efficiency and climate neutrality, with a gradual withdrawal from fossil fuels. However, it is not always easy to align these targets at Member State level and to create the appropriate national regulatory framework. Therefore, this article in the light of the two most recent judgements of the Constitutional Court of the Republic of Latvia (hereinafter – Constitutional Court), analyses the importance of a fixed term of state aid for electricity production and some aspects of state aid for biogas cogeneration plants, including the development of EU law perspective. The article also examines the impact of the enforcement of the Constitutional Court’s judgments in the area of state aid in Latvia and explains the emerging concept of environmental constitutionalism.
Legal Aspects of Membership in a Trade Union: A Case Study of Lithuania
Authors: Mačernytė-Panomariovienė Ingrida , Krasauskas Rytis 
Published: October 2024

The aim of this article is to address the questions of how the principle of freedom of association and the prohibition of discrimination on the basis of trade union membership are understood and to identify legal obstacles for an effective implementation of the right to join trade unions. International, EU regional and Lithuanian national legislation, as well as the case law of the European Court of Human Rights, the Court of Justice of the European Union and Lithuanian courts have been explored to carry out the current study. The results confirm that membership can be interpreted broadly; therefore, members of a trade union may be required to possess certain working and legal capacities, as well as meet other requirements related to the trade union’s objectives, which are sometimes unreasonable. Due to possible exceptions, various members may be subject to different collective rights, for example, certain officers may not be permitted to strike, and some may not even be allowed to join associations.
A Turning Point in the Understanding of the Legal Consequences of the Conclusion of a Preliminary Contract in Latvian Case Law
Authors: Kalniņš Erlens , Pavlovskis Germans 
Published: October 2024

On 5 July 2023, the Supreme Court (Senate) delivered its judgement in case No. SKC-19/2023, departing from the current case law regarding the legal understanding and legal consequences of a preliminary contract, regulated in Section 1541 of the Civil Law, recognising that both the right to claim conclusion of the main contract and the right to claim compensation for losses could arise from the preliminary contract, as well as providing other important findings, inter alia, regarding the possibility for the claimant to join the claim for conclusion of the main contract in one with the claim for performance of the main contract. This article provides detailed insight into this judgement by the Senate, at the same time referring to the findings made in the current case law and legal literature, as well as pointing to possible future challenges.
Disinformation in the EU Law: Moral Theories and the Context
Authors: Baltrimas Johanas 
Published: October 2024

In recent years, there have been scandalous cases of information warfare acts in the Western world committed by hostile foreign governments. The effect of such acts is dramatically amplified by the widespread use of the internet media and ongoing military conflicts. Accordingly, the EU has taken steps in the battle against disinformation. The legal definition of disinformation contains attributes that need further explanation, particularly, lying and deception. Philosophical theories contain valuable insights on the morality of lying and deception, which can be adapted for interpretation of the disinformation concept.