bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting cytotoxic lymphocyte antigen 4 (CTLA-4) in breast cancer
Authors: Jama Maryam , Tabana Yasser , Barakat Khaled H. 
Published: July 2024

AbstractBreast cancer (BC) has a high mortality rate and is one of the most common malignancies in the world. Initially, BC was considered non-immunogenic, but a paradigm shift occurred with the discovery of tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in the BC tumor microenvironment. CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) immunotherapy has emerged as a treatment option for BC, but it has limitations, including suboptimal antitumor effects and toxicity. Research has demonstrated that anti-CTLA-4 combination therapies, such as Treg depletion, cancer vaccines, and modulation of the gut microbiome, are significantly more effective than CTLA-4 monoclonal antibody (mAB) monotherapy. Second-generation CTLA-4 antibodies are currently being developed to mitigate immune-related adverse events (irAEs) and augment antitumor efficacy. This review examines anti-CTLA-4 mAB in BC, both as monotherapy and in combination with other treatments, and sheds light on ongoing clinical trials, novel CTLA-4 therapeutic strategies, and potential utility of biomarkers in BC.
Graphical Abstract
Quantifying functional redundancy in polysaccharide-degrading prokaryotic communities
Authors: Li Dan-dan , Wang Jianing , Jiang Yiru , Zhang Peng , Liu Ya , Li Yue-zhong , Zhang Zheng 
Published: July 2024

Abstract
Background
Functional redundancy (FR) is widely present, but there is no consensus on its formation process and influencing factors. Taxonomically distinct microorganisms possessing genes for the same function in a community lead to within-community FR, and distinct assemblies of microorganisms in different communities playing the same functional roles are termed between-community FR. We proposed two formulas to respectively quantify the degree of functional redundancy within and between communities and analyzed the FR degrees of carbohydrate degradation functions in global environment samples using the genetic information of glycoside hydrolases (GHs) encoded by prokaryotes.

Results
Our results revealed that GHs are each encoded by multiple taxonomically distinct prokaryotes within a community, and the enzyme-encoding prokaryotes are further distinct between almost any community pairs. The within- and between-FR degrees are primarily affected by the alpha and beta community diversities, respectively, and are also affected by environmental factors (e.g., pH, temperature, and salinity). The FR degree of the prokaryotic community is determined by deterministic factors.

Conclusions
We conclude that the functional redundancy of GHs is a stabilized community characteristic. This study helps to determine the FR formation process and influencing factors and provides new insights into the relationships between prokaryotic community biodiversity and ecosystem functions.
A novel variant in GAS2 is associated with autosomal dominant nonsyndromic hearing impairment in a Chinese family
Authors: Zhang Luping , Zheng Danya , Xu Lian , Wang Han , Zhang Shuqiang , Shi Jianhua , Jin Nana 
Published: July 2024

AbstractKnockout of GAS2 (growth arrest-specific protein 2), causes disorganization and destabilization of microtubule bundles in supporting cells of the cochlear duct, leading to hearing loss in vivo. However, the molecular mechanism through which GAS2 variant results in hearing loss remains unknown. By Whole-exome sequencing, we identified a novel heterozygous splicing variant in GAS2 (c.616–2 A > G) as the only candidate mutation segregating with late-onset and progressive nonsyndromic hearing loss (NSHL) in a large dominant family. This splicing mutation causes an intron retention and produces a C-terminal truncated protein (named GAS2mu). Mechanistically, the degradation of GAS2mu via the ubiquitin-proteasome pathway is enhanced, and cells expressing GAS2mu exhibit disorganized microtubule bundles. Additionally, GAS2mu further promotes apoptosis by increasing the Bcl-xS/Bcl-xL ratio instead of through the p53-dependent pathway as wild-type GAS2 does, indicating that GAS2mu acts as a toxic molecule to exacerbate apoptosis. Our findings demonstrate that this novel variant of GAS2 promotes its own protein degradation, microtubule disorganization and cellular apoptosis, leading to hearing loss in carriers. This study expands the spectrum of GAS2 variants and elucidates the underlying pathogenic mechanisms, providing a foundation for future investigations of new therapeutic strategies to prevent GAS2-associated progressive hearing loss.
A machine-learning regional clustering approach to understand ventilator-induced lung injury: a proof-of-concept experimental study
Authors: Cruces Pablo , Retamal Jaime , Damián Andrés , Lago Graciela , Blasina Fernanda , Oviedo Vanessa , Medina Tania , Pérez Agustín , Vaamonde Lucía , Dapueto Rosina , González-Dambrauskas Sebastian , Serra Alberto , Monteverde-Fernandez Nicolas , Namías Mauro , Martínez Javier , Hurtado Daniel E. 
Published: July 2024

Abstract
Background
The spatiotemporal progression and patterns of tissue deformation in ventilator-induced lung injury (VILI) remain understudied. Our aim was to identify lung clusters based on their regional mechanical behavior over space and time in lungs subjected to VILI using machine-learning techniques.

Results
Ten anesthetized pigs (27 ± 2 kg) were studied. Eight subjects were analyzed. End-inspiratory and end-expiratory lung computed tomography scans were performed at the beginning and after 12 h of one-hit VILI model. Regional image-based biomechanical analysis was used to determine end-expiratory aeration, tidal recruitment, and volumetric strain for both early and late stages. Clustering analysis was performed using principal component analysis and K-Means algorithms. We identified three different clusters of lung tissue: Stable, Recruitable Unstable, and Non-Recruitable Unstable. End-expiratory aeration, tidal recruitment, and volumetric strain were significantly different between clusters at early stage. At late stage, we found a step loss of end-expiratory aeration among clusters, lowest in Stable, followed by Unstable Recruitable, and highest in the Unstable Non-Recruitable cluster. Volumetric strain remaining unchanged in the Stable cluster, with slight increases in the Recruitable cluster, and strong reduction in the Unstable Non-Recruitable cluster.

Conclusions
VILI is a regional and dynamic phenomenon. Using unbiased machine-learning techniques we can identify the coexistence of three functional lung tissue compartments with different spatiotemporal regional biomechanical behavior.
From virtually extinct to superabundant in 35 years: establishment, population growth and shifts in management focus of the Swedish wild boar (Sus scrofa) population
Authors: Bergqvist Göran , Kindberg Jonas , Elmhagen Bodil 
Published: July 2024

AbstractBackgroundThe wild boar (Sus scrofa) was extinct in Sweden when a few animals established in the 1970s. Over the past 35 years, the species has made a substantial comeback. In this paper, we analyse wild boar population growth using three indices of population size. We also map the legislative decisions and research prompted by the expanding population. We discuss to what extent, in the eyes of the state, the view of wild boar and the management focus has shifted over time, from a perceived pest (eradication) to scarce (conservation), overabundant (reduction/control) or somewhere in between (sustainable management).ResultsWild boar harvest started in the early 1990s with a few hundred animals annually and peaked at 161,000 in 2020/2021. The distribution now comprises most of southern Sweden. Analyses of harvest and traffic accidents involving wild boar showed that the population grew exponentially until 2010/2011, after which the increase levelled off. Thus, logistic growth models showed the best fit for the full study period. We recorded 38 legislative decisions or commissions to government agencies regarding wild boar. The first decision in 1981 was to eradicate the free-ranging population. In 1987 however, the parliament decided that wild boar is native to Sweden and should be allowed in restricted extent. Later decisions mainly concerned hunting regulations and hunting methods as direct means to increase harvest and regulate the population. Another topic, increasing in importance over time, was to facilitate the use of wild boar meat to indirectly stimulate harvest. A local outbreak of African swine fever in 2023 necessitated a stamping out strategy in the affected area. We found 44 scientific papers regarding the present free-ranging population. Topics include movements and feeding patterns, hunting, reproduction, and population development.ConclusionsThe state historically regarded wild boar as a pest to be eradicated. This changed with the decision that wild boar should be allowed in restricted extent, suggesting a conservation approach. In response to population growth, the focus shifted to means facilitating sustainable management and, lately, reducing growth. The story of wild boar in Sweden illustrates attempts to mitigate conflicts and balance interests in wildlife management.
Strengthening access to cancer medicines for children in East Africa: policy options to enhance medicine procurement, forecasting, and regulations
Authors: Petricca Kadia , Carson Laura , Kambugu Joyce , Denburg Avram 
Published: July 2024

AbstractGaps in access to quality essential medicines remain a major impediment to the effective care of children with cancer in low-and middle-income countries (LMICs). The World Health Organization reports that less than 30% of LMICs have consistent availability of childhood cancer medicines, compared to over 95% in high-income countries. Information provided within this policy brief is drawn from a review of the literature and a mixed-methods study published in the Lancet Oncology that analyzed determinants of cancer medicine access for children in Kenya, Tanzania, Uganda, and Rwanda. Three key policy options are presented to guide strategic policy direction and critical health system planning for strengthening access to cancer medicines for children: pooled procurement, evidence-based forecasting, and regional harmonization of regulatory processes. Enhancing regional pooled procurement to address fragmented markets and improve medicine supply, investing in health information systems for improved forecasting and planning of childhood cancer medicine needs, and promoting regulatory harmonization to streamline medicine approval and quality assurance across East Africa are recommended. This policy brief is intended for policymakers, clinicians, and health-system planners involved in the procurement, supply chain management, policy and financing of childhood cancer medicines.
Urban governance arrangements for sustainability and justice – linking theory with experience
Authors: Kramer Jakob , Silverton Sophia , Späth Philipp 
Published: July 2024

AbstractThe Leipzig Charter highlights the need for integrated, place-based participatory governance approaches to achieve more sustainable and just urban futures. In this article, we provide a synthesis of our transdisciplinary analysis of ten EU projects which were selected from over 100 EU-funded urban sustainability and justice projects. Through analysing these cases according to the question of ‘How can city makers design governance processes for just and sustainable outcomes?’, we identify six Enabling Governance Arrangements which are considered of high relevance to the integration of urban sustainability and justice through both municipality and community-led initiatives. Each Enabling Governance Arrangement was not only observed at play in multiple initiatives but was also further consolidated and confirmed in dedicated workshops with over 60 city makers of different backgrounds. This highlights their potential to stir place-specific debates around the governance of sustainable and just cities. Overall, we provide empirically grounded, actionable insights for policymakers, practitioners, and researchers on how to achieve integrated urban sustainability and justice through Enabling Governance Arrangements.
miR-146a and miR-155 as promising biomarkers for prognosis and diagnosis of multiple sclerosis: systematic review
Authors: Rajabi Soroush , Sadegi Kambiz , Hajisobhani Sara , Kaveh Mania , Taghizadeh Eskandar 
Published: July 2024

Abstract
Background
Small RNA molecules known as microRNAs (miRNAs) regulate gene expression during the post-translational steps. miRNAs are essential for many physiological processes, such as cell division, growth, and proliferation, as well as development and metabolism.

Aims
To review the developments in investigations on miR-155 and miR-146a as possible biomarkers for multiple sclerosis (MS) disease diagnosis and prognosis.

Methods
A comprehensive analysis of the available literature was carried out by searching databases including PubMed, Scopus, and Web of Science for papers published between 2011 and 2023 years. Only original articles written in the English language were considered for inclusion in this review.

Results
A total of 29 studies were initially identified, with 14 meeting the inclusion criteria.

Conclusion
The present study underscores the crucial role of microRNAs, particularly miR-155 and miR-146a, in the etiology and progression of multiple sclerosis (MS). Through an extensive analysis of the literature, we have found compelling evidence linking aberrations in the expression and function of these microRNAs to MS pathogenesis. Specifically, our synthesis suggests that miR-155 and miR-146a hold promise as valuable biomarkers for both the diagnosis and prognosis of MS. Despite the challenges posed by the heterogeneity of MS subtypes, the non-invasive accessibility of miRNAs in various bodily fluids, including serum, peripheral blood, cerebrospinal fluid, and extracellular vesicles, presents a promising avenue for the development of robust diagnostic and prognostic tools. By elucidating the intricate roles of miR-155 and miR-146a in MS, our findings contribute to advancing our understanding of the disease mechanisms and pave the way for the development of more effective diagnostic and therapeutic strategies.
Outcomes following endorectal pull-through for Hirschsprung disease: a retrospective study
Authors: AbouZeid Amr Abdelhamid , AbdelMalek Amr AbdelRahman 
Published: July 2024

Abstract
Purpose
To share our experience in the surgical management of patients with Hirschsprung disease (HD) using the trans-anal endorectal pull-through “Soave” technique.

Methods
The study included cases diagnosed as HD who were operated during the period 2008 through 2018. Cases of total colonic aganglionosis were excluded to be discussed in a separate report.

Results
The study included 67 consecutive cases of HD. All included cases underwent trans-anal endorectal pull-through which was purely trans-anal in 31 (46%), while abdominal-assisted trans-anal endorectal pull-through was applied in the remaining (54%). Early postoperative complications included 2 cases of partial dehiscence at the colo-anal anastomosis; 1 of them deteriorated after re-exploration and unfortunately died. Twenty-six cases were available to assess functional outcomes after corrective surgery. Their age at follow-up ranged between 44 months and 17 years (mean = 78.8 months; median = 72 months). All cases achieved voluntary defecation. However, fecal soiling was a common finding after surgery for HD (69%). Constipation was another common postoperative finding (73%). Lastly, a history of attacks of postoperative enterocolitis was prevalent in 19 cases (73%), which ranged between 1 and 7 attacks usually in the first 2 years after the operation.

Conclusion
The trans-anal endorectal pull-through provides an effective surgical treatment for Hirschsprung disease. The high prevalence of fecal soiling after surgery highlights the importance of long-term follow-up to provide the required support for these patients during adolescence and transition into adulthood.
Rare presentation of recurrent ovarian carcinoma with secondary Budd–Chiari syndrome: a case report
Authors: Damini S. , Chandrashekhara S. H. , Ray M. D. 
Published: July 2024

Abstract
Background
Budd–Chiari syndrome (BCS) is a rare condition, usually associated with hematological disorders such as thrombotic diathesis and hypercoagulability. Serum CA-125 level is an established tumor marker of ovarian malignancy; however, cases of primary BCS may also show raised CA-125 levels. BCS in a case of ovarian carcinoma is usually primary in nature due to hypercoagulable state, and raised CA-125 levels with tender hepatomegaly in a treated case of ovarian carcinoma usually imply metastatic recurrence in the liver. However, our case demonstrates an atypical secondary cause of BCS in such a patient caused by extrinsic compression of IVC due to recurrent disease.

Case presentation
We report an unusual case of a 69-year-old female who presented with nausea and abdominal pain. She had a 7-year-old history of endometrioid carcinoma of the right ovary for which she underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic lymph node dissection along with adjuvant chemotherapy. Currently, she had right hypochondrium tenderness, deranged liver function tests (LFT) and raised CA-125 levels, which raised suspicion of hepatic metastasis. However, CECT abdomen revealed peripheral mottled enhancement of liver with multifocal extrahepatic tumor deposits, one of them causing compression of inferior vena cava (IVC) implying a diagnosis of secondary Budd–Chiari syndrome.

Conclusions
In a background of treated ovarian malignancy with raised CA-125 levels and deranged LFT, primary suspicion is of hepatic tumor recurrence. However, in our case, radiological investigation revealed diagnosis of secondary Budd–Chiari syndrome due to perihepatic metastatic recurrence with the absence of frank intrahepatic lesions.
Factors influencing utilization of physiotherapy services by health care providers at Busia County Referral Hospital in Kenya
Authors: Eyinda Johnstone Milimo , Myezwa Hellen , Sekome Kganetso 
Published: July 2024

Abstract
Background
The surging trend of noncommunicable diseases complicated by trauma and infectious diseases has left many with marked physical limitations. Physiotherapy component of primary health care could be utilized for management of both communicable and noncommunicable diseases to restore physical functions.

Objectives
To establish the health care providers’ level of knowledge and factors that influence the utilization of physiotherapy services among community members of Busia County in Kenya. The association between level of knowledge and demographic profile of health care providers at BCRH was also established.

Method
Descriptive cross-sectional quantitative study involved 192 participants (nurses, doctors, and clinical officers) who were purposively selected. They completed self-administered questionnaire between August and November 2019. They were both sexes above 18 years of age, drawn from Busia County Referral Hospital. Data was analysed by Microsoft Excel and SPSS version 25.

Results
The majority (92%) of the health care service providers had adequate knowledge about physiotherapy from their training to working with likelihood ratio chi-square of 7.714 with p-value at 0.01 at 5% level of significant. They had excellent communication (86.03%) with physiotherapists and helped to refer patients at BCRH for physiotherapy (χ2 = 52.02 and p-value = 0.01) at 5% level of significant. They had trust (91.56%) that physiotherapists were knowledgeable enough to handle patients on their own.

Conclusion
The health care service providers are knowledgeable about the importance of physiotherapy and have supported its utilization. However, there is need to integrate physiotherapy service at all levels of training and practice of the components of primary health care. This will lead to a holistic patient’s care in terms of preventive, curative, and rehabilitative. Quality of life for the community members will be enhanced for appropriate functionality to meet the population needs. Lower utilization of physiotherapy services in Busia County could be due to factors associated with dynamics within the community and the health care service providers.
Immune-phenotyping of peripheral blood mononuclear cells from patients with early triple-negative breast cancer: Identification of a systemic immunosuppressive CD3+ CD4+ CD39+ Treg subset.
Authors: Rapoport Bernardo Leon , Chicken Nicole , Meyer Pieter , Anderson Ronald , Heyman Liezl , Smit Teresa , Worsley Catherine 
Published: July 2024

3040 Background: Cells of the immune system and malignant cells interact in the tumor microenvironment, influencing response to treatment and survival. The current study was undertaken to assess the prevalence of these immune cells systemically in patients with early triple-negative breast cancer (TNBC). Methods: Multi-parameter flow cytometry was used to examine the percentages and phenotypes of cytotoxic T cells, natural killer (NK) cells, monocyte subsets, and regulatory T cell (Treg) subsets in the peripheral blood of 19 TNBC patients (pts) and 10 controls (cnt). Multicolor flow cytometry was carried out using DURAClone IM phenotyping (basic and Treg tubes) with a CytoFLEX Flow Cytometer (Beckman Coulter, California, USA), and data analyzed with FlowJo v 10.10.0 software (BD Life Sciences, USA). The Mann-Whitney U-test was used to compare non-parametric data where appropriate. Results: Significant increases in the percentages of immunosuppressive CD3+ CD4+ CD39+ Tregs cells in the setting of a significant decrease of CD19+ B cells were observed in pts with TNBC (Table).Tumour size, nodal status, age and ki-67 did not correlate with the percentages of any type of circulating immune cell. Conclusions: TNBC is associated with severe immunosuppression. In this context, percentages of circulating CD19+ B cells were significantly lower, while CD3+ CD4+ CD39+ Tregs were significantly higher in early TNBC pts. The peripheral blood immunome of TNBC pts identified a subset of immunosuppressive Tregs. A study is ongoing to identify the prognostic and predictive values of this systemic subset of Tregs for pCR in early TNBC pts undergoing neoadjuvant chemotherapy. [Table: see text]