bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile synthesis of copper nitroprusside chitosan nanocomposite and its catalytic reduction of environmentally hazardous azodyes
Authors: El Mously Dina A. , Mahmoud Amr M. , Khallaf Moustafa Ali , Mandour Howida S. , Batakoushy Hany A.
Published: July 2024

One of the biggest issues affecting the entire world currently is water contamination caused by textile industries’ incapacity to properly dispose their wastewater. The presence of toxic textile dyes in the aquatic environment has attracted significant research interest due to their high environmental stability and their negative effects on human health and ecosystems. Therefore, it is crucial to convert the hazardous dyes such as methyl orange (MO) azo dye into environmentally safe products. In this context, we describe the use of Copper Nitroprusside Chitosan (Cu/SNP/Cts) nanocomposite as a nanocatalyst for the chemical reduction of azodyes by sodium borohydride (NaBH4). The Cu/SNP/Cts was readily obtained by chemical coprecipitation in a stoichiometric manner. The X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT-IR) spectroscopy were applied to investigate chemical, phase, composition, and molecular interactions. Additionally, Scanning electron microscope (SEM) was used to examine the nanomaterial's microstructure. UV–vis spectroscopy was utilized for studying the Cu Nitroprusside Chitosan's catalytic activity for the reduction of azodye. The Cu/SNP/Cts nanocomposite demonstrated outstanding performance with total reduction time 160 s and pseudo-first order constant of 0.0188 s−1. Additionally, the stability and reusability study demonstrated exceptional reusability up to 5 cycles with minimal activity loss. The developed Cu/SNP/Cts nanocomposite act as efficient nanocatalysts for the reduction of harmful Methyl orange azodye.
Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury
Authors: Chen Jiating , Zhang Chi , Yang Zihan , Wu Weiling , Zou Weihao , Xin Zixuan , Zheng Shuyu , Liu Runchun , Yang Lili , Peng Hongjuan
Published: July 2024

Background

Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage.

Methods

Vimentin gene knockout (vim−/−) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim−/− and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection.

Results

Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8+ T cells and the secretion of interferon-gamma.

Conclusion

Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.

Graphical Abstract
Mitochondrial genome of the fluke pond snail, Austropeplea cf. brazieri (Gastropoda: Lymnaeidae)
Authors: Sukee Tanapan , Koehler Anson V. , Webster Bonnie L. , Gauci Charles G. , Fogarty Conor E. , Ponder Winston F. , Gasser Robin B. , Young Neil D.
Published: July 2024

Background

Lymnaeid snails of the genus Austropeplea are an important vector of the liver fluke (Fasciola hepatica), contributing to livestock production losses in Australia and New Zealand. However, the species status within Austropeplea is ambiguous due to heavy reliance on morphological analysis and a relative lack of genetic data. This study aimed to characterise the mitochondrial genome of A. cf. brazieri, an intermediate host of liver fluke in eastern Victoria.

Methods

The mitochondrial genome was assembled and annotated from a combination of second- and third-generation sequencing data. For comparative purposes, we performed phylogenetic analyses of the concatenated nucleotide sequences of the mitochondrial protein-coding genes, cytochrome c oxidase subunit 1 and 16S genes.

Results

The assembled mt genome was 13,757 base pairs and comprised 37 genes, including 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The mt genome length, gene order and nucleotide compositions were similar to related species of lymnaeids. Phylogenetic analyses of the mt nucleotide sequences placed A. cf. brazieri within the same clade as Orientogalba ollula with strong statistical supports. Phylogenies of the cox1 and 16S mt sequences were constructed due to the wide availability of these sequences representing the lymnaeid taxa. As expected in both these phylogenies, A. cf. brazieri clustered with other Austropeplea sequences, but the nodal supports were low.

Conclusions

The representative mt genome of A. cf. brazieri should provide a useful resource for future molecular, epidemiology and parasitological studies of this socio-economically important lymnaeid species.

Graphical abstract
Overwintering West Nile virus in active Culex pipiens mosquito populations in Greece
Authors: Balatsos Georgios , Beleri Stavroula , Tegos Nikolaos , Bisia Marina , Karras Vasileios , Zavitsanou Evangelia , Papachristos Dimitrios P. , Papadopoulos Nikos T. , Michaelakis Antonios , Patsoula Eleni
Published: July 2024

The flavivirus West Nile Virus (WNV), which is transmitted by mosquitoes, poses a significant threat to both humans and animals, and its outbreaks often challenge public health in Europe and other continents. In recent years, there is an increasing trend of WNV incidence rates across several European countries. However, whether there is a year-round circulation or seasonal introduction has yet to be elucidated. Real-time polymerase chain reaction (PCR) identified WNV-positive Culex pipiens mosquitos in 6 out of 146 pools examined in winter 2022 that correspond to three out of the 24 study areas, located in two coastal regions units in Attica, Greece. Spatial dispersion of the six positive pools in the same region suggests a clustered circulation of WNV during the winter of 2022. This is the first study that documents the identification of WNV in Cx. pipiens populations, captured in adult traps during winter period. Our findings underscore the need to extend entomological surveillance programs to include the winter period, specifically in temperate climates and historically affected areas by WNV.

Graphical Abstract
Cognitive reappraisal and affective response to physical activity: associations with physical activity behavior
Authors: Gürdere Ceren , Sorgenfrei Julina , Pfeffer Ines
Published: July 2024

Objective

Cognitive reappraisal (CR), as an adaptive emotion regulation strategy, may play a role in transforming affect in a positive direction during or after exercise, thereby supporting physical activity (PA) adherence. The present study aimed to test the associations among PA, CR frequency, and affective response to PA, and further to examine the role of CR on PA behavior through affective response.

Methods

A cross-sectional study was conducted with a sample of 105 adults, 74 of whom were women, with a mean age of 25.91. Self-report scales were used to measure PA, CR, and affective response to PA. Along with scales, demographic questions on age, sex, and education level were included. Data was collected via an online questionnaire.

Results

The frequency of CR use was positively associated with affective response, and affective response with PA behavior. Mediation analysis revealed that affective response mediated the relationship between CR and PA.

Discussion

Results were in the expected direction demonstrating the mediating role of affective response between CR and PA which implies that PA adherence might be facilitated by CR engagement. PA intervention programs should consider implementing CR ability and use frequency improving techniques.
Autophagy modulation effect on homotypic transfer of intracellular components via tunneling nanotubes in mesenchymal stem cells
Authors: Sadeghsoltani Fatemeh , Avci Çığır Biray , Hassanpour Parisa , Haiaty Sanya , Rahmati Mohamad , Mota Ali , Rahbarghazi Reza , Nemati Maryam , Mahdipour Mahdi , Talebi Mehdi , Takanlou Leila Sabour , Takanlou Maryam Sabour , Mehdizadeh Amir
Published: July 2024

Background

Recent studies have proved the role of autophagy in mesenchymal stem cell (MSCs) function and regenerative properties. How and by which mechanism autophagy modulation can affect the juxtacrine interaction of MSCs should be addressed. Here, the role of autophagy was investigated in the formation of tunneling nanotubes (TNTs) and homotypic mitochondrial donation.

Methods

MSCs were incubated with 15 µM Metformin (Met) and/or 3 µM 3-methyladenine (3-MA) for 48 h. The formation of TNTs was assessed using bright-field and SEM images. The mitochondria density and ΔΨ values were monitored using flow cytometry analysis. Using RT-PCR and protein array, the close interaction and shared mediators between autophagy, apoptosis, and Wnt signaling pathways were also monitored. The total fatty acid profile was assessed using gas chromatography.

Result

Data indicated the increase of TNT length and number, along with other cell projections after the induction of autophagy while these features were blunted in 3-MA-treated MSCs (p < 0.05). Western blotting revealed the significant reduction of Rab8 and p-FAK in 3-MA-treated MSCs (p < 0.05), indicating the inhibition of TNT assembly and vesicle transport. Likewise, the stimulation of autophagy increased autophagic flux and mitochondrial membrane integrity compared to 3-MA-treated MSCs. Despite these findings, protein levels of mitochondrial membrane Miro1 and 2 were unchanged after autophagy inhibition/stimulation (p > 0.05). We found that the inhibition/stimulation of autophagy can affect the protein, and transcription levels of several mediators related to Wnt and apoptosis signaling pathways involved in different cell bioactivities. Data confirmed the profound increase of mono and polyunsaturated/saturated fatty acid ratio in MSCs exposed to autophagy stimulator.

Conclusions

In summary, autophagy modulation could affect TNT formation which is required for homotypic mitochondrial donation. Thus, the modulation of autophagy creates a promising perspective to increase the efficiency of cell-based therapies.
NOX4-mediated astrocyte ferroptosis in Alzheimer’s disease
Authors: Maimaiti Yasenjiang , Su Ting , Zhang Zhanying , Ma Lingling , Zhang Yuan , Xu Hong
Published: July 2024

This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer’s Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4’s role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aβ and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.
Targeting cytotoxic lymphocyte antigen 4 (CTLA-4) in breast cancer
Authors: Jama Maryam , Tabana Yasser , Barakat Khaled H.
Published: July 2024

Breast 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

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

Knockout 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

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

Background

The 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).

Results

Wild 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.

Conclusions

The 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

Gaps 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

The 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

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

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

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

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]
Association of KRAS G12D vs. G12V circulating tumor DNA variant allele fraction and real-world overall survival in metastatic non-small cell lung and colorectal cancers.
Authors: Till Jacob Edward , Bucheit Leslie A , Zhang Nicole , Clemens Keelia M. , Carpenter Erica L.
Published: July 2024

3041

Background: We previously reported KRAS G12D but not G12V variant allele fraction (VAF), as measured in circulating tumor DNA (ctDNA), was associated with overall survival (OS) in metastatic treatment-naïve pancreatic cancer (mPDAC). However, this has not been examined in other RAS-driven cancers. Here we assessed association of real-world OS (rwOS) with KRAS G12D and G12V VAF in metastatic colorectal cancer (mCRC) and non-small cell lung cancer (mNSCLC). Methods: We queriedGuardantINFORM, a real-world evidence database of aggregated commercial payer health claims and de-identified results from Guardant360 (G360) ctDNA testing from 2014 to 2023, to identify mNSCLC/mCRC patients who were treatment-naive and had KRAS G12D or G12V mutations identified < 30 days prior to first-line therapy initiation. Those with co-occurring KRAS alterations, KRAS amplifications, and/or MSI-H were excluded. Outcomes were assessed as above vs. below median VAF and stratified by treatment type. The Cox regression model was run for continuous VAF, adjusting for age, gender, summary comorbidity score [Elixhauser Comorbidity Index (ECI)], and year of G360. Results: For mCRC, KRAS VAF above median was significantly associated with shorter rwOS for both G12D and G12V (Table 1); subgroup analysis of the predominant standard-of-care chemotherapy, FOLFOX, showed similar findings. For mNSCLC, KRAS VAF above median was associated with shorter rwOS for G12V, but not G12D (Table). Subgroup analysis by first-line treatment type revealed this association to be similar for chemotherapy-containing regimens but not immunotherapy (IO) alone. Conclusions: While a variant-specific association of KRAS VAF with rwOS was observed in mNSCLC overall (G12V associated, G12D not), above vs below median VAF was not associated with rwOS for the subset of patients receiving IO only. In contrast, for mCRC both G12D and G12V VAF were associated with rwOS, including for the subset of patients who received chemotherapy. These data suggest a complex interplay between KRAS variant, ctDNA shedding, first-line treatment, and OS that will be important in the interpretation of the prognostic implications of ctDNA-identified KRAS alterations. [Table: see text]
Ethnic and clinical differences in gBRCA and HRD mutated breast and ovarian cancers and their response to PARP inhibitors.
Authors: Uttamchandani Ashok , Syed Naveed , Chintakuntlawar Ashish Vittalrao , Afrooz Imrana , Uttam Chandani Kanishka , Hasan Riad Al , Vilasini Deepthi , Salami Aisha Mohamed Al , Chehal Aref Ahmad
Published: July 2024

e13102

Background: Hereditary mutations of the homologous recombination (HR), the key DNA double-strand break repair pathway, are one of the well-known causes of breast and ovarian cancers. Few reports exist on these mutations and the utilization of PARP inhibitors in the Middle Eastern region. Methods: This is a single-center retrospective study of breast and ovarian cancer patients who underwent genetic testing for g BRCA and HR defects (HRD) respectively between August 2021 and May 2023. Data was summarized using descriptive statistics and compared using counts and percentages. Response to treatment was assessed using RECIST criteria. Results: The prevalence of pathogenic mutations was 22.8%, with 26.3% of breast cancers harboring g BRCA mutations and 24% of ovarian cancers showing HRD positivity. Middle Eastern patients comprised 40% of the g BRCA-positive breast cancer group, while Asians accounted for 66% of the HRD-positive ovarian cancer patients. In mutated breast cancer, 53.3% had a positive family history of cancer. 33.3% of mutated breast cancer group and 66.6% of the ovarian cancer group received PARPis. Objective response to PARPi was 40% and 100% in breast and ovarian cancers, respectively. Conclusions: Our study revealed a high prevalence of g BRCA mutations (26.3%) in breast cancer and HRD positivity (24%) in ovarian cancer). Ethnic profiles differed between these cancers, with Middle Eastern and Southeast Asian patients dominating the breast and ovarian groups, respectively. Interestingly, the TNBC rate in breast cancer remained around 20% regardless of g BRCA status. While disparities between HRD groups were more pronounced in ovarian cancer, as expected, unexpected trends emerged in breast cancer. Further research with larger cohorts is needed to confirm these findings. [Table: see text]
Percutaneous cryoablation of breast cancer metastases: Analysis of long-term single center experience, efficacy and outcomes.
Authors: Chi Jie , Aoun Hussein , Chen Wei , Zong Yu , Ristic Gorica , Jang Hyejeong , Simon Michael S. , Assad Hadeel
Published: July 2024

e13105

Background: Percutaneous image-guided cryoablation is a minimally invasive loco-regional treatment modality with wide availability and advantages of minimal sedation, short recovery, and ability to continue concurrent systemic therapy. However, there is a paucity of data about its long-term effects in the treatment of metastatic breast cancer despite evidence suggesting a potential survival advantage with loco-regional therapy for oligo-metastatic disease. Methods: We conducted retrospective analysis of patients who underwent CT-guided percutaneous cryoablation for metastatic breast cancer and had at least 1 follow up post cryoablation. Patient data including demographics, cancer treatment history and outcomes were extracted by chart review after IRB approval. Descriptive analyses of overall survival (OS), progression-free survival (PFS), and time to next-line treatment (TTNL) was performed. Results: The study encompassed 37 metastatic breast cancer patients who underwent cryotherapy between 2004-2021. These ablation procedures targeted various metastatic sites, which included the liver, lung, renal, lymph nodes, subcutaneous nodules, and bone. Their median age at the time of cryoablation was 58 years (range: 34-90). Among them, 46% had triple-negative breast cancer (TNBC), 41% were HR+/HER2-, and 8% were HER2+. Prior to first cryoablation procedure, 59% of patients had received more than one line of systemic therapy, and 73% were actively undergoing systemic treatment. The median size of the metastatic lesions treated with cryoablation was 1.8 cm (range: 0.4-6.5 cm). The most frequent site for cryotherapy was the liver (38%), followed by lymph nodes (30%). For the entire cohort, median PFS, TTNL, and OS were 7.1, 14, and 65.7 months, respectively. Subgroup analysis revealed mPFS of 3.1, 7.4 and 14.2 months for TNBC, Her2+ and HR+/Her2- cohorts respectively. Subgroup analysis for OS was not reported due to the small number of events and premature follow up time. Among the 27 patients who experienced disease progression, the majority (74%) had distant progression, with 22% occurring within the same organ but outside the ablation zone. Local recurrence within the ablation zone was rare, observed in only 4% of cases. Conclusions: Percutaneous image-guided cryoablation of metastatic breast cancer lesions demonstrated durable local response, prolonged PFS, TTNL and OS. Future studies investigating cryoablation as part of a multidisciplinary treatment approach for patients with metastatic breast cancer are worthwhile to confirm disease control rate and improvement in survival.
Effect of tumorspheres cultured from circulating cancer stem cells on the innate checkpoint CD47 in patients with breast cancer.
Authors: Pizon Monika , Schott Dorothea , Pachmann Ulrich A. , Pachmann Katharina
Published: July 2024

e13113

Background: Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies reported that increased expression of CD47 enable cancer cells to evade phagocytosis by macrophages and promote the cancer stem cell phenotype. Understanding the mechanisms behind this CD47 overexpression in cancer stem cells is critical for developing more effective immunotherapy. Therefore, in the current study, we evaluated the incidence and clinical relevance of tumorspheres cultured from cCSCs expressing CD47 in breast cancer patients. Methods: 110 patients with breast cancer in different stages of disease were included in this study. The determination of cCSCs was performed using the sphere-forming assay. Additionally, anti-CD47 antibody staining was applied to examine CD47 expression on breast tumorspheres. Results: We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres was associated with disease progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p<0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p<0.05). CD47 was highly expressed in tumorspheres, which are enriched from circulating cancer stem cells and associated with triple-negative tumors. We also observed high heterogeneity of CD47 expression between the tumorspheres of a patient and between the patients. Conclusions: The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with high expression of CD47 might suggest their immunoregulatory potential. Better understanding of the interaction between cCSCs and tumor immunology may improve outcome especially in high-risk patients in part by attacking cCSCs and disinhibiting innate immunity.
Are we ready to use PSMA as a theranostic biomarker in clinical practice for patients with breast cancer?
Authors: Bravaccini Sara , Virga Alessandra , Foca Flavia , Cortecchia Stefania , Martinelli Giovanni , Ravaioli Sara , Tumedei Maria Maddalena , Matteucci Federica , Maltoni Roberta , Paganelli Giovanni , Poli Francesca , Mazza Massimiliano , Nicolini Fabio , Ulivi Paola , Sansovini Maddalena , Caroli Paola , Puccetti Maurizio
Published: July 2024

e13114

Background: Subtype classification for breast cancer (BC) patients is important for risk-stratification. Unfortunately, this parameter is not able to discriminate perfectly between high- and low-risk disease and the identification of an accurate biomarker to determine aggressiveness is still a clinical need. Prostate-specific membrane antigen (PSMA) could be important given that it has been reported to be expressed in BC tumor cells and even more in endothelial cells of tumor vessels. Methods: We analyzed 101 BCs of whom 22 luminal A, 34 Luminal B, 22 HER2 positive and 23 triple negative (TN) BC to assess whether PSMA expression by immunohistochemistry was different in tumor subtypes and was related to ki67 expression and stromal (tumour-infiltrating lymphocytes) TILs. PSMA positivity was calculated as the number of positive vessels on 10 fields at 40X magnifications. Kruskal Wallis’s test was used to assess difference in PSMA positivity among BC subgroups and Dunn’s test was performed for post-hoc comparisons; Spearman’s rho coefficient was calculated to analyze the correlation among PSMA, KI67 and TILs. Results: The median age at diagnosis of BC patients was 66 (min-max: 25-87 years). Seventy (69.3%) patients had ER>0 and 64 (63.4%) had PgR>0. The ductal histotype was present in 92 patients (91%). The majority of the patients had grade 3 tumors (55.4%). Considering the number of positive vessels, our results showed that median PSMA was higher in TNBC compared to Luminal A, Luminal B and HER2 positive tumors (p<0.001, p=0.001 and p=0.041, respectively). Ki67 was higher in TNBC compared to Luminal A, Luminal B and HER2 positive tumors (p<0.001, p<0.001 and p=0.001, respectively). We saw a correlation between PSMA and ki67, especially in HER2 positive tumors (p<0.001), while a correlation between PSMA and TILs was observed in Luminal A (p=0.028). The analysis of PSMA expression on the lymph nodes showed the same trend observed for the primary tumors given that it was higher in TNBC compared to HER2 positive and luminal cancers. Conclusions: Our results suggest that PSMA could be used as a theranostic biomarker in BC considering that it is highly expressed in more aggressive tumors and the possibility to treat PSMA expressing patients for anti-angiogenesis and/or radionuclide treatment.