bluuebunny/crossref_metadata_2025 huggingface dataset:
miR-876-3p is a tumor suppressor on 9p21 that is inactivated in melanoma and targets ERK
Authors: Bezrookove Vladimir , Khan Imran , Bhattacharjee Anukana , Fan Juifang , Jones Robyn , Sharma Anima , Nosrati Mehdi , Desprez Pierre-Yves , Salomonis Nathan , Shi Yihui , Dar Altaf , Kashani-Sabet Mohammed
Published: August 2024

Background

While melanomas commonly harbor losses of 9p21, on which CDKN2A resides, the presence of additional tumor suppressor elements at this locus is incompletely characterized. Here we assess the expression levels and functional role of microRNA-876-3p (miR-876), whose gene also maps to 9p21.

Methods

Expression of miR-876 was assessed in human tissues and cell lines using quantitative miRNA reverse transcriptase polymerase chain reaction (qRT-PCR). MIR876 copy number was determined in The Cancer Genome Atlas (TCGA) melanoma cohort. The consequences of regulation of miR-876 expression were assessed on melanoma cell colony formation, migration, invasion, apoptosis, cell cycle progression, and drug sensitivity in culture, and on in vivo tumor growth in a xenograft model. Genome-wide transcriptomic changes induced by miR-876 overexpression were determined using RNA sequencing (RNA-Seq).

Results

miR-876 expression was significantly decreased in primary melanoma samples when compared with nevi, and in human melanoma cell lines when compared with human melanocytes. Analysis of the TCGA cohort revealed deletions in MIR876 in > 50% of melanomas. miR-876 overexpression resulted in decreased melanoma cell colony formation, migration, and invasion, which was accompanied by cell cycle arrest and increased apoptosis. Intra-tumoral injections of miR-876 significantly suppressed melanoma growth in vivo. RNA-Seq analysis of miR-876-treated tumors revealed downregulation of several growth-promoting genes, along with upregulation of tumor suppressor genes, which was confirmed by qRT-PCR analysis. Computational analyses identified MAPK1 (or ERK2) as a possible target of miR-876 action. Overexpression of miR-876 significantly suppressed luciferase expression driven by the MAPK1/ERK2 3’ UTR, and resulted in decreased ERK protein expression in melanoma cells. MAPK1/ERK2 cDNA overexpression rescued the effects of miR-876 on melanoma colony formation. miR-876 overexpression sensitized melanoma cells to treatment with the BRAF inhibitor vemurafenib.

Conclusions

These studies identify miR-876 as a distinct tumor suppressor on 9p21 that is inactivated in melanoma and suggest miR-876 loss as an additional mechanism to activate ERK and the mitogen activated protein kinase (MAPK) pathway in melanoma. In addition, they suggest the therapeutic potential of combining miR-876 overexpression with BRAF inhibition as a rational therapeutic strategy for melanoma.
Loss of clear cell characteristics in aggressive clear cell odontogenic carcinoma: a case report
Authors: Sun Yanan , Li Bo , Hu Yaying , Chen Fu , Pan Junchen , Zhou Yi , Zhang Jiali
Published: August 2024

Background

Clear cell odontogenic carcinoma (CCOC) is an odontogenic carcinoma characterized by sheets and islands of vacuolated and clear cells. The diagnosis of atypical CCOC can pose a challenge when tumor cells deviate from their characteristic clear morphology, even with the aid of genetic profiling for CCOC identification.

Case presentation

In this manuscript, we detailed the inaugural instance of a recurrently recurring clear cell odontogenic carcinoma (CCOC) with pronounced squamous differentiation in a 64-year-old male. The primary tumor in this individual initially displayed a biphasic clear cell phenotype. However, subsequent to the third recurrence, the clear tumor cells were entirely supplanted by epidermoid cells characterized by eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Notable aggressive attributes such as necrosis, conspicuous cytological malignancy, perineural dissemination, and vascular invasion were noted. Additionally, the tumor progressed to manifest lung metastases. The tumor cells exhibited positive immunoreactivity for AE1/AE3, KRT19, Pan-CK, EMA, P40, P63, CK34βE12, and P53, while they tested negative for CK35βH11, KRT7, S-100, and neuroendocrine markers. The Ki-67 proliferation index was calculated at an average of 15%. Furthermore, FISH analysis unveiled the presence of the EWSR1::ATF1 gene fusion.

Conclusions

This case illustrated a rare and aggressive case of CCOC characterized by significant squamous differentiation upon recurrence of the tumor.
Burden of illness in Rett syndrome: initial evaluation of a disorder-specific caregiver survey
Authors: Kaufmann Walter E. , Percy Alan K. , Neul Jeffrey L. , Downs Jenny , Leonard Helen , Nues Paige , Sharma Girish D. , Bartolotta Theresa E. , Townend Gillian S. , Curfs Leopold M. G. , Mariotti Orietta , Buda Claude , O’Leary Heather M. , Oberman Lindsay M. , Vogel-Farley Vanessa , Barnes Katherine V. , Missling Christopher U.
Published: August 2024

Background

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder associated with multiple neurologic impairments. Previous studies have shown challenges to the quality of life of individuals with RTT and their caregivers. However, instruments applied to quantify disease burden have not adequately captured the impact of these impairments on affected individuals and their families. Consequently, an international collaboration of stakeholders aimed at evaluating Burden of Illness (BOI) in RTT was organized.

Methods

Based on literature reviews and qualitative interviews with parents of children and adults with RTT, a caregiver questionnaire was constructed to evaluate 22 problems (inclusive of core characteristics, functional impairments, and comorbidities) often experienced with RTT, rated mainly with a 5-level Likert scale. The questionnaire was administered anonymously online to an international sample of 756 caregivers (predominantly parents) of girls and women with RTT. Descriptive statistics were used to identify problems of high frequency and impact on affected individuals and caregivers. Chi-square tests characterized the relationship between problem severity and impact responses, while nonparametric ANOVAs of raw and z-score adjusted scores identified agreement between severity and impact on individual and caregiver. Secondary inferential tests were used to determine the roles of age, clinical type, and country of residence on BOI in RTT.

Results

There was variability in reported frequency of problems, with the most prevalent, severe and impactful being those related to the core features of RTT (i.e., communication and fine and gross motor impairments). Chi-square analyses demonstrated interdependence between severity and impact responses, while ANOVAs showed that many problems had disproportionately greater impact than severity, either on affected individuals (e.g., hand stereotypies) or their caregivers (e.g., sleep difficulties, seizures, pain, and behavioral abnormalities). With certain exceptions (e.g., breath-holding, seizures), age, clinical type, or country of residence did not influence these BOI profiles.

Conclusions

Our data demonstrate that core features and related impairments are particularly impactful in RTT. However, problems with mild severity can also have disproportionate impact on affected individuals and, particularly, on their caregivers. Future analyses will examine the role of factors such as treatment outcomes, healthcare services, and healthcare provider’s perspectives, in these BOI profiles.
Transcriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson’s disease
Authors: Dehestani Mohammad , Kozareva Velina , Blauwendraat Cornelis , Fraenkel Ernest , Gasser Thomas , Bansal Vikas
Published: August 2024

Several prior studies have proposed the involvement of various brain regions and cell types in Parkinson’s disease (PD) pathology. Here, we performed snRNA-seq on the prefrontal cortex and anterior cingulate regions from a small cohort of post-mortem control and PD brain tissue. We found a significant association of oligodendrocytes (ODCs) and oligodendrocyte precursor cells (OPCs) with PD-linked risk loci and report several dysregulated genes and pathways, including regulation of tau-protein kinase activity, regulation of inclusion body assembly and protein processing involved in protein targeting to mitochondria. In an independent PD cohort with clinical measures (681 cases and 549 controls), polygenic risk scores derived from the dysregulated genes significantly predicted Montreal Cognitive Assessment (MoCA)-, and Beck Depression Inventory-II (BDI-II)-scores but not motor impairment (UPDRS-III). We extended our analysis of clinical outcome prediction by incorporating differentially expressed genes from three separate datasets that were previously published by different laboratories. In the first dataset from the anterior cingulate cortex, we identified an association between ODCs and BDI-II. In the second dataset obtained from the substantia nigra (SN), OPCs displayed an association with UPDRS-III. In the third dataset from the SN region, a distinct subtype of OPCs, labeled OPC_ADM, exhibited an association with UPDRS-III. Intriguingly, the OPC_ADM cluster also demonstrated a significant increase in PD samples. These results suggest that by expanding our focus to glial cells, we can uncover region-specific molecular pathways associated with PD symptoms.
Building a performance measurement framework for telephone triage services in Finland: a consensus-making study based on nominal group technique
Authors: Vainio Hanna , Soininen Leena , Torkki Paulus
Published: August 2024

Background

There has been a significant expansion in the measurement of healthcare system performance. However, there is a lack of a comprehensive performance measurement framework to assess the effects of telephone triage services on the urgent care system. The aim of our Delphi study was to construct and validate a performance measurement framework designed explicitly for telephone triage services.

Methods

This study was conducted in Finland with a group of eight experienced senior physicians from the country's 20 largest joint emergency departments, serving over 90% of the population for urgent care. The Nominal Group Technique (NGT) was utilised to achieve consensus on measuring telephone triage performance. Initially, performance indicators (PIs) were identified through Delphi method rounds from December 10th to December 27th, 2021, with eight experts participating, and from December 29th, 2021, to January 23rd, 2022, where five of these experts responded. NGT further deepened these themes and perspectives, aiding in the development of a comprehensive performance measurement framework. The final framework validation began with an initial round from February 13th to March 3rd, 2022, receiving five responses. Due to the limited number of responses, an additional validation round was conducted from October 29th to November 7th, 2023, resulting in two more responses, increasing the total number of respondents in the validation phase to seven.

Results

The study identified a strong desire among professionals to implement a uniform framework for measuring telephone triage performance. The finalised framework evaluates telephone triage across five dimensions: service accessibility, patient experience, quality and safety, process outcome, and cost per case. Eight specific PIs were established, including call response metrics, service utility, follow-up care type and distribution, ICPC-2 classified encounter reasons, patient compliance with follow-up care, medical history review during assessment, and service cost per call.

Conclusions

This study validated a performance measurement framework for telephone triage services, utilising existing literature and the NGT method. The framework includes five key dimensions: patient experience, quality and safety, outcome of the telephone triage process, cost per case, and eight PIs. It offers a structured and comprehensive approach to measuring the overall performance of telephone triage services, enhancing our ability to evaluate these services effectively.
Catheters linked thrombosis in neonates: a single center observational study
Authors: Farag Marwa Mohamed , Ghazal Hesham Abd El Rahim , Radwan Mohamed Masoud , El-sayed Nada Saeid
Published: August 2024

Background

Central venous catheters (CVCs) are the major risk factors for neonatal thrombosis that might negatively affect morbidity and mortality in neonates. The aim of the present work was to estimate the incidence of CVC-linked thrombosis, among neonates in the NICU of Alexandria University Maternity Hospital, Egypt, over 1year, and to determine its possible risk factors.

Methods

This observational cohort study involved 134 newborn infants born from July 2020 to July 2021with CVCs insertion during their hospital stay. Patients who had congenital anomalies, had thrombosis unrelated to the implantation of CVCs or died before 7 days of catheter placement were excluded from the analysis. The 134 neonates who met the study’s eligibility requirements had 142 CVCs inserted. Serial ultrasound and Doppler scans on site of venous insertion of catheters were performed.

Results

Seventeen patients with catheter’s thrombosis (12%) were found during the placement of 142 catheters or 1615 CVCs’ days, resulting in an overall rate of 10.5 thrombotic events per 1000 catheters’ days. We constructed a logistic regression model to identify risk factors behind CVC-linked thrombosis. In univariate analysis, femoral central venous lines (CVLs), catheter dwell-time, sepsis, packed red cells (PRBCs) transfusions and low platelet count were risk factors for CVC-linked thrombosis. Nevertheless, only PRBCs transfusion was significant in the multivariate analysis, with OR and 95% confidence level 5.768 (1.013–32.836).

Conclusion

Many factors should be considered in prediction of patients at risk of thrombosis including sepsis, femoral line insertion, low platelet count and PRBCs-transfusions. In our analysis, PRBCs-transfusion through peripheral intravenous lines (PIVs) was the strongest factor associated with CVC-linked thrombosis.
The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma
Authors: Moragas Núria , Fernandez-Nogueira Patricia , Recalde-Percaz Leire , Inman Jamie L. , López-Plana Anna , Bergholtz Helga , Noguera-Castells Aleix , del Burgo Pedro J. , Chen Xieng , Sorlie Therese , Gascón Pere , Bragado Paloma , Bissell Mina , Carbó Neus , Fuster Gemma
Published: August 2024

Background

A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.

Methods

We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.

Results

We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.

Conclusions

Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.
Hepatocellular adenomas with severe intra-abdominal bleeding, related to an underlying coagulation disorder: a case report
Authors: Oudmaijer C. A. J. , Sprakel J. , Sprengers D. , Wiese K. A. , Tintel N. Vogelaar - , Franken J. I. , Terkivatan T. , Porte R. J. , IJzermans J. N. M.
Published: August 2024

Background

Hepatocellular adenoma is a rare benign liver tumor. Typically, hepatocellular adenomas are solitary and are found in young women who use estrogen-containing contraceptives. The occurrence of multiple hepatocellular adenoma has been linked to higher body mass index, and as the prevalence of overweight increases, multiple hepatocellular adenomas are seen more often. An hepatocellular adenoma does not always necessitate treatment, as they can regress under conservative strategies. In incidental cases, an adenoma presents owing to bleeding, which is mostly self-limiting. If it is not, embolization of hepatic involved vessels is indicated.

Case presentation

In this case report, we discuss a 42-year old Caucasian woman with multiple hepatocellular bleeds, treated by multiple endovascular procedures. After the first embolization of an adenoma in the right liver lobe, a second bleed occurred in the left lobe, necessitating additional endovascular intervention. During admittance, treatment was complicated by pulmonary embolism and a pneumonia. During follow-up, our patient was diagnosed with antiphospholipid syndrome.

Conclusion

Hepatocellular adenoma is a rare diagnosis that requires centralized expertise. This particular case illustrates the complexity of treatment strategies for associated intra-abdominal bleeding and possible complications. Although liver adenoma is often an incidental finding, it can also result in significant morbidity. Centralization of treatment leads to expertise in managing complex treatment strategies.
Extended spectrum and metalo beta lactamase producing gram negative bacterial pathogens from cockroaches collected at hospital, Southern Ethiopia
Authors: Bisetegn Fithamlak Solomon , Azene Habtamu , Ahmed Khawaja Shakeel , Wadilo Fiseha , Tufa Efrata Girma
Published: August 2024

Background

Cockroaches can pose a significant health risk in hospital environments because they may serve as reservoirs and vectors for nosocomial pathogens. Cockroaches harbor epidemiologically significant extended spectrum and metalo beta lactamase producing Gram negative bacterial pathogens, which complicate nosocomial infections.

Objectives

The main aim of this study is to determine aetiology and phenotypic extended spectrum and metalo beta lactamase producing Gram negative bacteria pathogens from cockroaches collected in hospitals.

Methods

A cross-sectional study was employed from February to May 2022 to determine the antibiotic resistance producing bacterial isolates from cockroaches by giving special emphasis to metalo beta lactamase and extended spectrum beta lactamase production from different wards of WSUCSH. Cockroaches were collected with hands wearing sterile gloves. External homogenate was prepared and incubated microbiologically by using different culture media and differentiated biochemically. Antimicrobial susceptibility testing was performed by disk diffusion method. ESBL production was conducted using double disc synergy method and double disk method was used to detect MBL enzyme detection. Descriptive statistics was used to determine prevalence and percentage.

Result

Out of 245 cockroaches, 108 Gram negative bacteria were isolated. K. pneumoniae 29(26.9%) was the most predominant bacteria and Enetrobacter spp. 8(7.4%), was the least. All, K. pneumoniae, P. mirabilis, and Enterobacter isolates were pan-resistant to Ampicillin. P.aeruginosa and P.mirabilis antibiotics showed ≥ 80% resistant for amoxicillin/clavulanic acid antibiotics. Cefotaxime, ceftazidime, ceftriaxone and imipenem showed relative efficacy compared with other antibiotics. Out of 78 amoxicillin-clavulanic acid resistant isolates, 42(34.7%) were ESBL producers. ESBL production is more depicted by P. aeruginosa, A. baumannii, K. pneumoniae and E. coli. The overall prevalence of MBL production is 29(23.1%). K. pneumoniae P. aeruginosa, E.coli, A. baumannii, Enterobacter spp and K.oxytoca revealed MBL production.

Conclusion

The overall prevalence of ESBL and MBL producing nosocomial agents from hospital cockroaches was 34.7% and 23.1% respectively. P.aeruginosa, A.baumannii, K.pneumoniae and E.coli showed pronounced ESBL production. All bacterial isolates except P. mirabilis and C. freundii showed MBL production. The needed to evaluate our antibiotic stewardship program and antibiotic resistance detection for treatment is mandatory. The impact of cockroach as a source of AMR should be sought.
Trop2-targeted therapy in breast cancer
Authors: Hu Yixuan , Zhu Yinxing , Qi Dan , Tang Cuiju , Zhang Wenwen
Published: August 2024

Human trophoblastic cell surface antigen 2 (Trop2) is a glycoprotein, a cellular marker of trophoblastic and stem cells, and a calcium signaling transducer involved in several signaling pathways, leading to the proliferation, invasion, and metastasis of tumors. It is expressed at a low level in normal epithelial cells, but at a high level in many tumors, making it an ideal target for cancer therapy. According to previous literature, Trop2 is broadly expressed in all breast cancer subtypes, especially in triple negative breast cancer (TNBC). Several clinical trials have demonstrated the effectiveness of Trop2-targeted therapy in breast cancer. Sacituzumab govitecan (SG) is a Trop2-targeted antibody-drug conjugate (ADC) that has been approved for the treatment of metastatic TNBC and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This article reviews the structure and function of Trop2, several major Trop2-targeted ADCs, other appealing novel Trop2-targeted agents and relevant clinical trials to provide a landscape of how Trop2-targeted treatments will develop in the future.
Diffusion–based virtual MR elastography for predicting recurrence of solitary hepatocellular carcinoma after hepatectomy
Authors: Chen Jiejun , Sun Wei , Wang Wentao , Fu Caixia , Grimm Robert , Zeng Mengsu , Rao Shengxiang
Published: August 2024

Background

To explore the capability of diffusion-based virtual MR elastography (vMRE) in the preoperative prediction of recurrence in hepatocellular carcinoma (HCC) and to investigate the underlying relevant histopathological characteristics.

Methods

Between August 2015 and December 2016, patients underwent preoperative MRI examination with a dedicated DWI sequence (b-values: 200,1500 s/mm2) were recruited. The ADC values and diffusion-based virtual shear modulus (μdiff) of HCCs were calculated and MR morphological features were also analyzed. The Cox proportional hazards model was used to identify the risk factors associated with tumor recurrence. A preoperative radiologic model and postoperative model including pathological features were built to predict tumor recurrence after hepatectomy.

Results

A total of 87 patients with solitary surgically confirmed HCCs were included in this study. Thirty-five patients (40.2%) were found to have tumor recurrence after hepatectomy. The preoperative model included higher μdiff and corona enhancement, while the postoperative model included higher μdiff, microvascular invasion, and histologic tumor grade. These factors were identified as significant prognostic factors for recurrence-free survival (RFS) (all p < 0.05). The HCC patients with μdiff values > 2.325 kPa showed poorer 5-year RFS after hepatectomy than patients with μdiff values ≤ 2.325 kPa (p < 0.001). Moreover, the higher μdiff values was correlated with the expression of CK19 (3.95 ± 2.37 vs. 3.15 ± 1.77, p = 0.017) and high Ki-67 labeling index (4.22 ± 1.63 vs. 2.72 ± 2.12, p = 0.001).

Conclusions

The μdiff values related to the expression of CK19 and Ki-67 labeling index potentially predict RFS after hepatectomy in HCC patients.
Protocol for a pilot cluster randomised controlled trial of PRoGRAM-A (preventing gambling-related harm in adolescents): a secondary school-based social network intervention
Authors: Dobbie Fiona , Miller Martine , Wardle Heather , Dahlby Lucia , Weir Christopher , Niven Angela , Stoddart Andrew , Griffiths David , Lee Ashley , Good Sally , Noble Leon , White James
Published: August 2024

Background

In the UK, recent evidence of young people and gambling indicates a higher prevalence of gambling in comparison to other addictive behaviours. Engaging in gambling-related behaviour at a young age is associated with short and long-term consequences, including financial, emotional, academic, interpersonal, and physical and mental health detriments; otherwise known as gambling-related harms (GRH). Given the unique vulnerability of this younger group, early interventions aimed at delaying or preventing gambling are critical. PRoGRAM-A (Preventing Gambling-Related Harm in Adolescents) is a school-based, social network intervention to protect young people from future GRH, by delaying or preventing gambling experimentation.

Methods

Pilot cluster RCT with an embedded process evaluation and health economic scoping study.

Participants

PRoGRAM-A will be delivered in four schools, with two control schools acting as a comparator. All are secondary schools in Scotland. Baseline surveys were conducted with students in S3 (ages 13–14). Follow-up surveys were conducted with the same cohort, six months post-baseline.

Intervention

PRoGRAM-A trainers will deliver a 2-day, out-of-school training workshop to Peer supporters. Peer supporters will be nominated by peers among their school year group (S3, age 13–14). Workshops will provide peer supporters with information on four gambling-related topics: (1) what is gambling? (2) gambling and gaming, (3) gambling marketing, (4) identifying harm and reducing risk. Peer supporters will disseminate the information (message diffusion) they have learned among their friends and family over a 10-week period. After the 2-day workshop, PRoGRAM-A trainers will conduct × 3 in-school follow-up sessions with peer supporters to offer support, encouragement, and advice to Peer Supporters as well as monitor and explore the extent of their message diffusion.

Primary outcome

The primary outcome of the pilot cluster RCT (cRCT) will be whether progression to a phase III RCT is justified.

Discussion

This will be the first pilot cluster RCT (cRCT) of an intervention to prevent gambling-related harms among young people within the UK. If findings indicate feasibility and acceptability, funding will be sought for a phase III RCT of effectiveness.

Trial registration

Researchregistry8699. Registered 21st February 2023.
109Pd/109mAg in-vivo generator in the form of nanoparticles for combined β- - Auger electron therapy of hepatocellular carcinoma
Authors: Gharibkandi Nasrin Abbasi , Wawrowicz Kamil , Walczak Rafał , Majkowska-Pilip Agnieszka , Wierzbicki Mateusz , Bilewicz Aleksander
Published: August 2024

Background

Convenient therapeutic protocols for hepatocellular carcinoma (HCC) are often ineffective due to late diagnosis and high tumor heterogeneity, leading to poor long-term outcomes. However, recently performed studies suggest that using nanostructures in liver cancer treatment may improve therapeutic effects. Inorganic nanoparticles represent a unique material that tend to accumulate in the liver when introduced in-vivo. Typically, this is a major drawback that prevents the therapeutic use of nanoparticles in medicine. However, in HCC tumours, this may be advantageous because nanoparticles may accumulate in the target organ, where the leaky vasculature of HCC causes their accumulation in tumour cells via the EPR effect. On the other hand, recent studies have shown that combining low- and high-LET radiation emitted from the same radionuclide, such as 161Tb, can increase the effectiveness of radionuclide therapy. Therefore, to improve the efficacy of radionuclide therapy for hepatocellular carcinoma, we suggest utilizing radioactive palladium nanoparticles in the form of 109Pd/109mAg in-vivo generator that simultaneously emits β− particles and Auger electrons.

Results

Palladium nanoparticles with a size of 5 nm were synthesized using 109Pd produced through neutron irradiation of natural palladium or enriched 108Pd. Unlike the 109Pd-cyclam complex, where the daughter radionuclide diffuses away from the molecules, 109mAg remains within the nanoparticles after the decay of 109Pd. In vitro cell studies using radioactive 109Pd nanoparticles revealed that the nanoparticles accumulated inside cells, reaching around 50% total uptake. The 109Pd-PEG nanoparticles exhibited high cytotoxicity, even at low levels of radioactivity (6.25 MBq/mL), resulting in almost complete cell death at 25 MBq/mL. This cytotoxic effect was significantly greater than that of PdNPs labeled with β− (131I) and Auger electron emitters (125I). The metabolic viability of HCC cells was found to be correlated with cell DNA DSBs. Also, successful radioconjugate anticancer activity was observed in three-dimensional tumor spheroids, resulting in a significant treatment response.

Conclusion

The results indicate that nanoparticles labeled with 109Pd can be effectively used for combined β− - Auger electron-targeted radionuclide therapy of HCC. Due to the decay of both components (β− and Auger electrons), the 109Pd/109mAg in-vivo generator presents a unique potential in this field.
Measuring treatment impacts on symptoms in adults with hypoparathyroidism: findings from the PaTHway trial
Authors: Brod Meryl , Pfeiffer Kathryn M. , Beck Jane F. , Smith Alden
Published: August 2024

Background

Hypoparathyroidism is a rare endocrine disease frequently associated with serious physical and cognitive symptoms. This study’s purpose was to understand the impacts of the phase 3 PaTHway clinical trial treatment, TransCon PTH, on patients’ overall, physical, and cognitive hypoparathyroidism signs/symptoms and what patients consider meaningful improvement.

Methods

Individual telephone exit interviews were conducted with patients who recently completed the PaTHway trial blinded period. Using a semi-structured interview guide, interviews focused on trial treatment impact on hypoparathyroidism symptoms following the symptom list in the Hypoparathyroidism Patient Experience Scale-Symptom (HPES-Symptom). Meaningful changes in hypoparathyroidism symptoms were assessed with the Patient Global Impression of Severity (PGIS) and Patient Global Impression of Change (PGIC) measures. Interviewees were probed on the meaningfulness of reported changes in symptoms from prior to starting trial treatment to the past 2 weeks/current time. Interviews were audiotaped and transcribed. Transcripts were coded for emerging concepts and themes/subthemes covered in the interview guide based on an adapted grounded theory approach.

Results

Nineteen adults with hypoparathyroidism participated in interviews in the United States (n = 13, 68.4%) and Canada (n = 6, 31.6%). Marked improvements in physical and cognitive symptoms were described among trial treatment group respondents. The majority of participants who reported experiencing hypoparathyroidism physical symptoms pre-trial indicated symptom improvement with treatment, including muscle twitching (100%, n = 15), low energy (92.9%, n = 13), feeling tired (92.3%, n = 12), muscle weakness (92.9%, n = 13), tingling without numbness (84.6%, n = 11), trouble sleeping (92.3%, n = 12), muscle cramping (92.3%, n = 12), tingling with numbness (92.3%, n = 12), muscle spasms (100%, n = 12), and pain (90.9%, n = 10). Most participants who reported experiencing cognitive symptoms pre-trial reported symptom improvement with treatment, including difficulty finding the right words (86.7%, n = 13), difficulty concentrating (93.3%, n = 14), trouble remembering (92.9%, n = 13), trouble thinking clearly (85.7%, n = 12), and difficulty understanding information (83.3%, n = 10). Those in the placebo group reported limited or no improvement. The vast majority of participants affirmed that the improvements they experienced in symptom frequency on the PGIS/PGIC and HPES–Symptom were meaningful.

Conclusions

Findings indicate that TransCon PTH treatment improved participants’ physical and cognitive hypoparathyroidism symptoms in meaningful ways, while reducing the daily burden associated with conventional therapy.

Trial registration

NCT04701203 Registered: 06 January 2021. https://clinicaltrials.gov/study/NCT04701203?term=NCT04701203&rank=1.
Analysis of different bioactive compounds in the tissue of the epigeic earthworm, Eisenia fetida
Authors: Shetty Aishwarya , Biradar Pulikeshi M.
Published: August 2024

Background

Eisenia fetida is the epigeic earthworm renowned for organic waste management in vermitechnology. The medicinal properties of earthworm biomass is gaining much more importance in extracting various biomolecules. Therefore, the present study was carried out to analyze the bioactive compounds of Eisenia fetida by using gas chromatography and mass spectroscopy analysis of four different solvent extract and highlighting their biological activities.

Results

The analysis showed the presence of 17, 22, 21 and 18 bioactive compounds in chloroform, ethyl acetate, methanol and distilled water solvent extract, respectively. Each compound were analyzed based on their peak number, R-time and Base m/z values. The molecular formula, molecular weight, compound nature, their structure and biological activities were tabulated.

Conclusion

The presence of a wide range of bioactive compounds in the epigeic earthworm, Eisenia fetida, justifies the pharmacological use in curing various diseases.
Abundance and diversity of macro-invertebrates in the selected mangrove species along the coast of Mbegani in Bagamoyo District, Tanzania
Authors: Olotu Moses I. , Mganga Nyatwere D. , Simbili Abeli A.
Published: August 2024

Background

Mangrove forests are highly productive ecosystems that serve as biodiversity points, containing many organisations, contributing to carbon storage, improving water quality and providing ecosystem goods and services to improve local means of subsistence. These resilient ecosystems are characterised by their morphological modification and their particular respiratory structures (pneumatophores), which allow them to proliferate in salt-rich environments. Mangroves play a crucial role in maintaining invertebrate and fishery resources, providing shelter and nutrients to a diverse range of species. However, mangrove ecosystems are threatened by anthropogenic activities such as the extraction of building materials, firewood, crushing plants and salt manufacturing, resulting in the disintegration of ecosystems and the loss of inhabitants. This study aimed to determine the abundance and diversity of macro-benthic invertebrates on the different parts (roots, stems and leaves) of common mangrove species of the Mbegani coast, along the Indian Ocean using a completely randomised design.

Results

The sampling was done using a 1 m2 quadrat focussed on the three mangrove parts, viz. roots, stems and leaves. The results showed that the highest percentage of macro-invertebrates were recorded on Bruguera gymnorhiza (66.8%), followed by Avicennia marina (20.8%) and the least were Ceriops tagal (12.4%), such variation differed significantly between the three mangrove species across the selected plots (F(2,524) = 5.71, p = 0.035). The stems (54.4%) inhabited a large number of macro-invertebrates, followed by roots (32.8%) and the least were leaves (12.8%), which varied significantly between the three mangrove parts sampled across the selected mangrove species (F(2,524) = 7.25; p = 0.008). The majority of macro-invertebrates were planktonic feeders stuck on stems or herbivores shuttling between the roots and leaves of the plants. Macro-invertebrates recorded on Bruguiera gymnorhiza were more diverse than those found in C. tagal. The findings emphasise the importance of macro-invertebrates in the ecological balance of mangrove ecosystems.

Conclusion

The study concludes that mangroves in the Mbegani ecosystem have a high potential for biodiversity and are important for the coastal community and the ecosystem of the Bagamoyo District. The results contribute to coastal resources management programmes and future surveillance activities.
Accurate, automated classification of radiographic knee osteoarthritis severity using a novel method of deep learning: Plug-in modules
Authors: Lee Do Weon , Song Dae Seok , Han Hyuk-Soo , Ro Du Hyun
Published: August 2024

Background

Fine-grained classification deals with data with a large degree of similarity, such as cat or bird species, and similarly, knee osteoarthritis severity classification [Kellgren–Lawrence (KL) grading] is one such fine-grained classification task. Recently, a plug-in module (PIM) that can be integrated into convolutional neural-network-based or transformer-based networks has been shown to provide strong discriminative regions for fine-grained classification, with results that outperformed the previous deep learning models. PIM utilizes each pixel of an image as an independent feature and can subsequently better classify images with minor differences. It was hypothesized that, as a fine-grained classification task, knee osteoarthritis severity may be classified well using PIMs. The aim of the study was to develop this automated knee osteoarthritis classification model.

Methods

A deep learning model that classifies knee osteoarthritis severity of a radiograph was developed utilizing PIMs. A retrospective analysis on prospectively collected data was performed. The model was trained and developed using the Osteoarthritis Initiative dataset and was subsequently tested on an independent dataset, the Multicenter Osteoarthritis Study (test set size: 17,040). The final deep learning model was designed through an ensemble of four different PIMs.

Results

The accuracy of the model was 84%, 43%, 70%, 81%, and 96% for KL grade 0, 1, 2, 3, and 4, respectively, with an overall accuracy of 75.7%.

Conclusions

The ensemble of PIMs could classify knee osteoarthritis severity using simple radiographs with a fine accuracy. Although improvements will be needed in the future, the model has been proven to have the potential to be clinically useful.
The predictors of coronary slow flow in patients undergoing coronary angiography
Authors: Ermawan Romi , Pintaningrum Yusra , Indrayana Yanna
Published: August 2024

Background

A new challenge in coronary artery disease treatment has emerged, where specific populations exhibit ischemic symptoms without any obstruction in the epicardial coronary artery. Instead, they exhibit slow coronary contrast flow, referred to as coronary slow flow (CSF). This study aims to identify several predictors of CSF.

Results

This case–control study was conducted at the Regional General Hospital of West Nusa Tenggara Province in Indonesia from December 2016 to February 2024. The study involved sixty subjects, with 30 in each group of CSF and normal epicardial coronary artery angiogram (NECA). CSF is enforced by the TIMI frame count (TFC) greater than 27 frames. Among all the predictors studied, coronary artery diameter (p < 0.001) and random blood sugar (p = 0.049) were found to affect the CSF significantly. In the multivariate analysis, coronary artery diameter remained a significant predictor (adjusted OR 10.08, 95% CI 2.64–38.50, p < 0.001), with an optimal cut-off point of more than 3.56 mm, a sensitivity of 76.7%, and a specificity of 70.7% (AUC = 0.787, p < 0.001).

Conclusion

The coronary artery diameter strongly predicts CSF in patients undergoing coronary angiography.
Analysis of the association between the Slit2 biomarker and systemic lupus erythematosus
Authors: Farrag Sara , Mostafa Naema Mohamed , Mohamed Eman Safwat , Kamal Dalia Tarik , Abdelaziz Marwa Mahmoud
Published: August 2024

Background

To assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients.

Results

The mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients’ demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%.

Conclusion

While we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index.

Trial registration

NCT05105217. Registered 3 November 2021
Effects of HOX family regulator-mediated modification patterns and immunity characteristics on tumor-associated cell type in endometrial cancer
Authors: Yang JiaoLin , Li JinPeng , Li SuFen , Yang YuTong , Su HuanCheng , Guo HongRui , Lei Jing , Wang YaLin , Wen KaiTing , Li Xia , Zhang SanYuan , Wang Zhe
Published: August 2024

Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.
Cardiac calcified amorphous tumor in a patient with lung cancer
Authors: Hatori Kyohei , Mohara Jun , Shibata Satoru , Murata Miyuki , Fukuda Nobuaki , Hiroi Shitoshi , Koyano Tetsuya
Published: August 2024

Background

Calcified amorphous tumor of the heart is a rare non-neoplastic cardiac mass composed of calcified nodules over amorphous fibrous tissue with degeneration and some chronic inflammation. Calcified amorphous tumor is often associated with mitral annular calcification in patients with end-stage renal disease on dialysis. However, the exact etiology of calcified amorphous tumors remains uncertain.

Case presentation

A 77-year-old female with lung cancer showed a tumor with large mobility in the left ventricular outflow tract on transthoracic echocardiography. She had mitral annular calcification, although her renal function was normal. The tumor was excised surgically. Pathologically, the extracted specimen consisted of a calcified lesion without tumor tissue and was diagnosed as a calcified amorphous tumor.

Conclusions

As the patient had no other risk factors for calcified amorphous tumor except mitral annular calcification, we considered the association of blood coagulation abnormalities due to cancer-related thrombosis. This case suggests that calcified amorphous tumors may be associated with malignant tumors.
A new expression for fluid factor using AVO intercept and gradient: Theory and application on gas sand reservoirs from offshore Australia
Authors: Farfour Mohammed , Castagna John P.
Published: August 2024

Numerous amplitude variation with offset (AVO) fluid indicators have proven to be sensitive to the presence of hydrocarbons. Mathematically, these fluid indicators measure the deviation of seismic responses of hydrocarbon reservoirs from their background in a specific domain. We develop a new expression for the fluid factor commonly used in AVO analysis and interpretation. The expression is a function of the common AVO intercept and gradient, along with a weighting coefficient that suppresses the contribution of lithology and other factors unrelated to fluid content. The coefficient also assists in calibrating the fluid factor to the local geology. We compare the performance of our fluid factor with existing fluid factors. All the fluid factors are tested on a worldwide collection of P- and S-wave velocity and density measurements. The testing is followed by application on synthetic data before applying the attribute on real data from the Northwest Shelf of Australia. In the latter application on the real data, we use two wells for calibration purposes, and the third as a blind well. Our fluid factor demonstrated high capability in detecting the targeted gas zones at the three well locations and identifying new prospective zones.