bluuebunny/crossref_metadata_2025 huggingface dataset:
Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303/KEYNOTE-698 study
Authors: Cicin Irfan , Plimack Elizabeth R. , Gurney Howard , Leibowitz Raya , Alekseev Boris Y. , Parnis Francis X. , Peer Avivit , Necchi Andrea , Bellmunt Joaquim , Nishiyama Hiroyuki , Clark Jason , Munteanu Mihaela , Kataria Ritesh , Jia Calvin , Powles Thomas , Sternberg Cora N.
Published: July 2024

Background

Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%.

Methods

ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1.

Results

Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35–48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67–29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade ≥ 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent.

Conclusions

Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted.

Trial registration

ClinicalTrials.gov, NCT03374488. Registered 12/15/2017.
Determinants of wealth-related inequalities in full vaccination coverage among children in Nepal: a decomposition analysis of nationally representative household survey data
Authors: Singh Barun Kumar , Khatri Resham B.
Published: July 2024

Background

Over the past two decades, child health indicators in Nepal have improved significantly at the national level. Yet, this progress hasn’t been uniform across various population subsets. This study identified the determinants associated with childhood full vaccination, assessed wealth-related inequalities, and delved into the key factors driving this inequality.

Methods

Data for this study were taken from the most recent nationally representative Nepal Demographic and Health Survey 2022. A total of 959 children aged 12–23 months who had received routine childhood basic antigens as per the national immunisation program were considered for analysis. Binary logistic regression models were conducted to identify the associated factors with outcome variable (uptake of full vaccination). The concentration curve and Erreygers normalized concentration index were used to assess inequality in full vaccination. Household wealth quintile index scores were used to measure wealth-related inequality and decomposition analysis was conducted to identify determinants explaining wealth-related inequality in the uptake of childhood vaccination.

Results

The coverage of full vaccination among children was 79.8% at national level. Several factors, including maternal health service utilisation variables (e.g., antenatal care, institutional delivery), financial challenges related to visiting health facilities, and mothers’ awareness of health mother group meetings within their ward, were associated with the uptake of full vaccination coverage among children. The concentration curve was below the line of equality, and the relative Erreygers normalized concentration index was 0.090, indicating that full vaccination was disproportionately higher among children from wealthy groups. The decomposition analysis identified institutional delivery (20.21%), the money needed to visit health facilities (14.25%), maternal education (16.79%), maternal age (8.53%), and caste (3.03%) were important contributors to wealth related inequalities in childhood full vaccination uptake.

Conclusions

There was notable wealth-related inequality in full vaccine uptake among children in Nepal. Multisectoral actions involving responsible stakeholders are pivotal in reducing the inequalities, including promoting access to maternal health services and improving educational attainment among mothers from socioeconomically disadvantaged communities.
Antioxidant activity of polysaccharide from Garcinia mangostana rind and their derivatives
Authors: Tang Zhenjie , Huang Gangliang
Published: July 2024

Background

Polysaccharide from Garcinia mangostana rind has many biological activities and deserves further research.

Methods

The antioxidant properties of UAEE-GMRP, UAEE-GMRP-1 A, CM-30, and Ac-30 were evaluated through two different antioxidant activity experimental systems.

Results

The four polysaccharides had a better scavenging effect on hydroxyl radicals, while their inhibitory effect on lipid peroxidation was relatively weak. However, overall, the four polysaccharides showed a certain degree of potential application in the two antioxidant experiments mentioned above, especially the chemically modified polysaccharides from Garcinia mangostana rind, which effectively improved their antioxidant activity. This also indicates that chemical modification is a better method to improve polysaccharide activity. In addition, in these two antioxidant exploration experiments, carboxymethylated polysaccharide showed stronger activity compared to the other three polysaccharides.

Conclusion

The carboxymethylation modification may have great potential for application.
Humanization of the antigen-recognition domain does not impinge on the antigen-binding, cytokine secretion, and antitumor reactivity of humanized nanobody-based CD19-redirected CAR-T cells
Authors: Safarzadeh Kozani Pooria , Safarzadeh Kozani Pouya , Rahbarizadeh Fatemeh
Published: July 2024

Background

The immunogenicity of the antigen-recognition domains of chimeric antigen receptor (CAR)-T cells leads to immune responses that may compromise the antitumor effects of the adoptively transferred T cells. Herein, we attempt to humanize a CD19-specific VHH (named H85) using in silico techniques and investigate the impact of antigen-recognition domain humanization on CAR expression and density, cytokine secretion, and cytolytic reactivity of CAR-T cells based on the humanized VHH.

Methods

H85 was humanized (named HuH85), and then HuH85 was compared with H85 in terms of conformational structure, physicochemical properties, antigenicity and immunogenicity, solubility, flexibility, stability, and CD19-binding capacity using in silico techniques. Next, H85CAR-T cells and HuH85CAR-T cells were developed and CAR expression and surface density were assessed via flow cytometry. Ultimately, the antitumor reactivity and secreted levels of IFN-γ, IL-2, and TNF-α were assessed following the co-cultivation of the CAR-T cells with Ramos, Namalwa, and K562 cells.

Results

In silico findings demonstrated no negative impacts on HuH85 as a result of humanization. Ultimately, H85CAR and HuH85CAR could be surface-expressed on transduced T cells at comparable levels as assessed via mean fluorescence intensity. Moreover, H85CAR-T cells and HuH85CAR-T cells mediated comparable antitumor effects against Ramos and Namalwa cells and secreted comparable levels of IFN-γ, IL-2, and TNF-α following co-cultivation.

Conclusion

HuH85 can be used to develop immunotherapeutics against CD19-associated hematologic malignancies. Moreover, HuH85CAR-T cells must be further investigated in vitro and in preclinical xenograft models of CD19+ leukemias and lymphomas before advancing into clinical trials.
The multiple actions of dipeptidyl peptidase 4 (DPP-4) and its pharmacological inhibition on bone metabolism: a review
Authors: Pechmann L. M. , Pinheiro F. I. , Andrade V. F. C. , Moreira C. A.
Published: July 2024

Background

Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures.

Main body

The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y—both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals.

Conclusion

The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.
Exploring genetic association of systemic iron status and risk with incidence of diabetic neuropathy
Authors: Yu Xinyue , Jin Tianyu , Zhu Luyi , Guo Shunyuan , Deng Binbin , Cheng Yifan
Published: July 2024

Background

Diabetic neuropathy (DN), a frequent complication in individuals with diabetes mellitus (DM), is hypothesized to have a correlation with systemic iron status, though the nature of this relationship remains unclear. This study employs two-sample Mendelian randomization (MR) analysis to explore this potential genetic association.

Methods

We used genetic instruments significant associated with iron status including serum iron, ferritin, transferrin, and transferrin saturation, derived from an extensive Genome-Wide Association Study (GWAS) undertaken by the Genetics of Iron Status Consortium, involving a cohort of 48,972 European ancestry individuals. Summary statistics for DN were collected from a public GWAS, including 1,415 patients and 162,201 controls of European descent. Our MR analysis used the inverse-variance-weighted (IVW) method, supplemented by MR-Egger, weighted-median (WM) methods, Cochran’s Q test, MR-Egger intercept analysis, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and leave-one-out analysis to ensure robustness and consistency of the findings.

Results

No genetic causal relationship was found between iron status markers and DN (all IVW p value > 0.05). Interestingly, a causative effect of DN on ferritin (IVW: OR = 0.943, 95% CI = 0.892–0.996, p = 0.035) and transferrin saturation (IVW: OR = 0.941, 95% CI = 0.888–0.998, p = 0.044) emerged. Sensitivity analyses confirmed the absence of significant heterogeneity and horizontal pleiotropy.

Conclusion

While systemic iron status was not found to be causally related to DN, our findings suggest that DN may increase the risk of iron deficiency. These results provide further evidence supporting iron supplementation in patients with DN.
Effect of exercise on cluneal nerve entrapment neuropathy: a case report
Authors: Özüberk Burcu , Deniz Mine Argalı , Soyupek Feray Cinevre
Published: July 2024

Background

Low back pain is an important disability problem frequently encountered in the clinic. In the literature, it has been shown that neuropathic pain in chronic low back pain is quite common in patients. Although superior cluneal nerve entrapment syndrome is an underdiagnosed cause of low back and leg pain, differential diagnosis is very important anatomically and clinically. The superior cluneal nerves are pure sensory nerves that innervate the skin of the upper part of the buttocks. In the literature, methods such as surgery, nerve blockade, prolotherapy, and acupuncture have been used in the treatment of cluneal nerve entrapment syndrome, but there are no studies on exercise. In this case report, our aim is to explain the importance of differential diagnosis in cluneal nerve entrapment syndrome, which is one of the common causes of low back pain in the clinic, and the effects of exercise in this disease.

Case presentation

A 22-year-old, Turkish-ethnicity, male patient with complaints of low back pain, neck–back pain, and weakness did not use alcohol or cigarettes. In his family history, there was a history of diabetes in the mother and diabetes and heart failure in the father. He had a history of osteoporosis, epilepsy, asthma, sarcoidosis, and cardiac arrhythmia. The patient reported that he suffered from constipation three to four times a month. As a result of the detailed evaluation, the planned exercise prescription was taught to the patient, and after it was confirmed that the patient did the exercises correctly for 3 days, the exercise brochure was given and followed as a home exercise program for 8 weeks.

Conclusions

Lumbar stabilization exercises, gluteal muscle strengthening exercises, thoracolumbar fascia mobilization, and stretching exercises, which will be given in accordance with the clinical anatomy of the disease after the correct diagnosis in cluneal nerve entrapment syndrome, have been beneficial for the patient. However, we think that randomized controlled studies with a large sample will contribute to the literature.
A systematic review of public health interventions to address breast cancer inequalities in low- and middle-income countries
Authors: Chanakira Esther Z. , Thomas Chloe V. , Balen Julie , Mandrik Olena
Published: July 2024

Background

Breast cancer is the most diagnosed cancer in the world, with a worse prognosis documented in low- and middle-income countries. Inequalities pertaining to breast cancer outcomes are observed at within-country level, with demographics and socioeconomic status as major drivers.

Aim

This review aims to aggregate all available evidence from low- and middle-income countries on public health interventions that can be utilized to reduce breast cancer inequalities within the breast cancer continuum.

Methods

The study was a systematic review and narrative synthesis of available literature, with the literature search conducted between September and October 2021. The search was re-run in September 2022 to update the review. PubMed, Scopus, Embase, African Index Medicus and LILACS were searched, based on predetermined criteria. Randomized controlled trials, cohort studies and quasi-experimental studies were included for review, while studies without an intervention and comparator group were excluded. The Joanna Briggs Institute family of checklists was used for quality assessment of the included studies. Data pertaining to study design, quality control and intervention effectiveness was extracted.

Results

A total of 915 studies were identified for screening and 21 studies met the selection criteria. Only one study specifically evaluated the impact of an intervention on breast cancer inequalities. Diverse, multi-level interventions that can be utilized to address breast cancer inequalities through targeted application to disadvantaged subpopulations were identified. Educational interventions were found to be effective in improving screening rates, downstaging through early presentation as well as improving time to diagnosis. Interventions aimed at subsidizing or eliminating screening payments resulted in improved screening rates. Patient navigation was highlighted to be effective in improving outcomes throughout the breast cancer continuum.

Conclusion

Findings from the systematic review underline the importance of early detection in breast cancer management for low- and middle-income countries. This can be achieved through a variety of interventions, including population education, and addressing access barriers to public health services such as screening, particularly among under-served populations. This study provides a comprehensive database of public health interventions relevant to low- and middle-income countries that can be utilized for planning and decision-making purposes. Findings from the review highlight an important research gap in primary studies on interventions aimed at reducing breast cancer inequalities in low- and middle-income countries.

Systematic review registration

PROSPERO registration number: CRD42021289643.
Machine learning applied to species occurrence and interactions: the missing link in biodiversity assessment and modelling of Antarctic plankton distribution
Authors: Grillo Marco , Schiaparelli Stefano , Durazzano Tiziana , Guglielmo Letterio , Granata Antonia , Huettmann Falk
Published: July 2024

Background

Plankton is the essential ecological category that occupies the lower levels of aquatic trophic networks, representing a good indicator of environmental change. However, most studies deal with distribution of single species or taxa and do not take into account the complex of biological interactions of the real world that rule the ecological processes.

Results

This study focused on analyzing Antarctic marine phytoplankton, mesozooplankton, and microzooplankton, examining their biological interactions and co-existences. Field data yielded 1053 biological interaction values, 762 coexistence values, and 15 zero values. Six phytoplankton assemblages and six copepod species were selected based on their abundance and ecological roles. Using 23 environmental descriptors, we modelled the distribution of taxa to accurately represent their occurrences. Sampling was conducted during the 2016–2017 Italian National Antarctic Programme (PNRA) ‘P-ROSE’ project in the East Ross Sea. Machine learning techniques were applied to the occurrence data to generate 48 predictive species distribution maps (SDMs), producing 3D maps for the entire Ross Sea area. These models quantitatively predicted the occurrences of each copepod and phytoplankton assemblage, providing crucial insights into potential variations in biotic and trophic interactions, with significant implications for the management and conservation of Antarctic marine resources. The Receiver Operating Characteristic (ROC) results indicated the highest model efficiency, for Cyanophyta (74%) among phytoplankton assemblages and Paralabidocera antarctica (83%) among copepod communities. The SDMs revealed distinct spatial heterogeneity in the Ross Sea area, with an average Relative Index of Occurrence values of 0.28 (min: 0; max: 0.65) for phytoplankton assemblages and 0.39 (min: 0; max: 0.71) for copepods.

Conclusion

The results of this study are essential for a science-based management for one of the world’s most pristine ecosystems and addressing potential climate-induced alterations in species interactions. Our study emphasizes the importance of considering biological interactions in planktonic studies, employing open access and machine learning for measurable and repeatable distribution modelling, and providing crucial ecological insights for informed conservation strategies in the face of environmental change.
Experience sharing on perioperative clinical management of gastric cancer patients based on the “China Robotic Gastric Cancer Surgery Guidelines”
Authors: Ma Shixun , Fang Wei , Zhang Leisheng , Chen Dongdong , Tian Hongwei , Ma Yuntao , Cai Hui
Published: July 2024

Background

With the popularization of robotic surgical systems in the field of surgery, robotic gastric cancer surgery has also been fully applied and promoted in China. The Chinese Guidelines for Robotic Gastric Cancer Surgery was published in the Chinese Journal of General Surgery in August 2021.

Methods

We have made a detailed interpretation of the process of robotic gastric cancer surgery regarding the indications, contraindications, perioperative preparation, surgical steps, complication, and postoperative management based on the recommendations of China’s Guidelines for Robotic Gastric Cancer Surgery and supplemented by other surgical guidelines, consensus, and single-center experience.

Results

Twenty experiences of perioperative clinical management of robotic gastric cancer surgery were described in detail.

Conclusion

We hope to bring some clinical reference values to the front-line clinicians in treating robotic gastric cancer surgery.

Trial registration

The guidelines were registered on the International Practice Guideline Registration Platform (http://www.guidelines-registry.cn) (registration number: IPGRP-2020CN199).
Design, characterizations, and antimicrobial activity of sustainable home furnishing-based waste fabric treated using biobased nanocomposite
Authors: Swielam Eman M. , Hussien Zeinab M. , Hasanin Mohamed S.
Published: July 2024

Clothing and textile industries are major contributors to environmental pollution including textile manufacturing through garment production, spinning, weaving, and dyeing. In this context, the sustainability textile industry is a big challenge and contributes to serving a large segment of society. Also, textile wastes could be used as a raw material for added-value products. Herein, in this study, recycling of residues fabric was treated with antimicrobial nanocomposite to reach the best use of exhausts and obtain multifunction products of aesthetic via the technical design of the waste raw materials. Besides, solving the unemployment problem by opening fields for small industry projects capable of producing high-value textile artifacts, especially when treated against microbes, can be applied to home furnishings. The waste fabric was treated via green synthesis nanocomposite based on chitosan and in situ prepared ZnONPs and cross-linked with tannic acid. The prepared nanocomposite was characterized using physicochemical analysis including attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Additionally, the nanocomposite and treated fabric topographical behavior were studied using scanning electron microscopy (SEM) attachment with energy dispersive X-ray analysis (EDX), and images were processed to evaluate the roughness structure. Additionally, high-resolution transmission electron microscopy (HR-TEM) and dynamic light scattering (DLS) were performed to ensure the size and stability of the nanocomposite. The obtained results affirmed the green synthesis of nanocomposite with a size around 130 nm, as well as the doped ZnONPs average size of 26 nm and treated waste fabric, performed a promising attraction between nanocomposite and fabric fibers. Moreover, the antimicrobial study observed excellent activity of nanocomposite against bacteria and unicellular fungi as well.
Longitudinal changes of funduscopic optic disc size, color and cup-to-disc ratio in school children
Authors: Sameshima Seiji , Yamashita Takehiro , Terasaki Hiroto , Asaoka Ryo , Yoshihara Naoya , Kakiuchi Naoko , Sakamoto Taiji
Published: July 2024

Background

To investigate the relationship between changes in the optic disc size and color, cup-to-disc (C/D) ratio, and axial elongation in schoolchildren.

Methods

A prospective cohort study was performed in 75 right eyes of elementary school students for six years (from 8.5 to 14.5 years old). In the first and last year, all participants underwent optical axial length measurement and color fundus photography. The optic disc color was calculated by dividing the intensity of red by the sum of the intensity of red, green, and blue. The optic disc area was calculated by modifying the number of pixels according to Bennett’s formula. The C/D ratio was calculated by dividing the vertical cup diameter by vertical optic disc diameter. Wilcoxon signed rank test was used to compare these optic disc parameters and axial length in the first and last year.

Results

Mean axial length in the last year (24.82 mm) was significantly longer than that in the first year (23.34 mm). Likewise, the mean optic disc size was significantly smaller in the last year (41,946 pixels) than that in the first year (46,144 pixels). The mean optic disc color in the last year (0.49) was significantly more reddish than that in the first year (0.46), while the mean C/D ratio in last year (0.50) was significantly smaller than that in first year (0.52).

Conclusions

During the period from 8.5 years to 14.5 years of age, both the optic disc size and C/D ratio became smaller, while the color became more red.
Sex estimation using Magnetic Resonance Imaging measurements of hand and foot in Egyptian population
Authors: Amer Marwa Abd El-Moniem , Elhamed Marwa Elsayed Abd , Elhawy Lamiaa Lotfy , AbdAllah Amany Mohammed , Mohammad Nanies Sameeh , Bessar Manar A. , Elgebely Mohamed Nabil Soliman , Moawed Dena Mohamed Naguib Abdel
Published: July 2024

Background

The identification of skeletal remains begins with a sex evaluation since other biological profile elements, such as size and age, are sex-specific. The pelvis is the favored element for sex assessment since it is very sexually dimorphic.

Aim of the study

Delivering hand and foot bones sex estimate criteria for Egyptian population identification was the goal of this work.

Subject and methods

Eighty-two Egyptian adult subjects (41 males and 41 females) aged ≥ 21 years old were subjected to MRI scan on the right hand and foot to assess 9 measurements: hand length, hand width, four measurements of middle metacarpal bone (length, breadth, head breadth and base breadth), first metatarsal bone length, first metatarsal bone width and (first metatarsal bone length x first metatarsal bone width).

Results

All the measured parameters in the right hand and foot were higher in males than females. First metatarsal bone length x first metatarsal bone width in the foot and middle metacarpal bone breadth in the hand were the most sexually dimorphic parameters, with accuracy of 86.6 percent and 84.1 percent, respectively. In stepwise discriminant analysis, three of nine measurements were selected: First metatarsal bone length x first metatarsal bone width, middle metacarpal bone breadth and hand width for the sex prediction equation in the Egyptian population, with a cross-validated sex classification accuracy of 90.2%.

Conclusion

Sex can be assessed from hand and foot metric parameters measured by MRI with high accuracy.
Using the consolidated framework for implementation research to identify church leaders’ perspectives on contextual determinants of community-based colorectal cancer screening for Black Kentuckians
Authors: Kruse-Diehr Aaron J. , Cegelka Derek , Combs Carlee , Wood Rose , Holtsclaw Elizabeth , Stapleton Jerod L. , Williams Lovoria B.
Published: July 2024

Background

Black Kentuckians experience more deleterious colorectal cancer (CRC) outcomes than their White counterparts, a disparity that could be reduced by increased screening in Black communities. Previous research has shown that Black Kentuckians may not be equitably informed of different CRC screening options by health care providers, making community-based screening a potentially effective option among this disparate population. We used the Consolidated Framework for Implementation Research (CFIR) to identify church leaders’ perspectives of contextual factors that might influence community-based screening and explore the feasibility of using church-based screening outreach.

Methods

Six participants were selected, based on leadership roles and interest in CRC screening, from five established Louisville-area church partners that had previously participated in community health initiatives. Data were collected, both virtually and in-person, in Summer 2021 using semi-structured interview guides developed with guidance from the CFIR Guide that focused on domains most relevant to community-based interventions. Data were transcribed verbatim, coded by two independent researchers, and member checked for accuracy.

Results

Data were aligned primarily with six CFIR constructs: key stakeholders, champions, opinion leaders, tension for change, compatibility, and culture. Participants noted a strong tension for change in their community due to perceptions of inadequacy with clinical approaches to CRC screening. Additionally, they stressed the importance of identifying individuals both within the church who could champion CRC screening and help implement program activities, as well as those outside the church who could collaborate with other local organizations to increase participant reach. Finally, participants agreed that faith-based CRC screening aligned with church culture and would also likely be compatible with overall community values.

Conclusions

Overall, our church partners strongly endorsed the need for, and importance of, community-based CRC screening. Given a history of successful implementation of health promotion programs within our partner churches, it is highly likely that a CRC screening intervention would also be effective. Findings from this study will be used to identify implementation strategies that might positively impact a future faith-based CRC screening intervention, as well as CFIR constructs that are most positively associated with CRC screening completion.
Characterization of three African swine fever viruses from different clinical settings revealed a potential attenuation mechanism
Authors: Zhang Jiajia , Wang Yuening , Zhang Kaili , Deng Dafu , Peng Kai , Zheng Wanglong , Chen Nanhua , Liu Penggang , Shang Shaobin , Li Ruichao , Zhu Jianzhong
Published: July 2024

African swine fever (ASF) is an acute and fatal hemorrhagic disease in domestic pigs and wild boars caused by African swine fever virus (ASFV) that currently threatens the pig industry worldwide. Since the 2018 ASF outbreak in China, ASFV has evolved and caused diverse clinical manifestations, such as chronic and asymptomatic infections. Therefore, it is important to understand the molecular mechanisms underlying ASFV attenuation in the field. Here, we isolated three ASFVs from one diseased and two asymptomatic pigs by using primary porcine alveolar macrophages (PAMs) from both domestic pigs and Bama minipigs. The three ASFVs exhibited similar phenotypes in cell culture, including cytopathic effects (CPEs), hemadsorptions (HADs), viral protein expressions and growth curves. Genome sequencing revealed that all three ASFVs were genotype II strains. Genomic comparisons suggested that the disruption of the viral genes MGF360 and MGF110, rather than EP402R and EP153R, is likely involved in the potential attenuation of ASFV via the upregulation of innate immune responses.
Imperfect diffusion-controlled reactions for stochastic processes with memory
Authors: Mendes T. V. , Guérin T.
Published: July 2024

Many physical processes are controlled by the time that a random walker needs to reach a target. In many practical situations, such as reaction kinetics, this target is imperfect: multiple random encounters may be necessary to actually trigger a reaction. So far, most analytical approaches of imperfect reaction kinetics have been limited to Markovian (memoryless) stochastic processes. However, as soon as the random walker interacts with its environment, its motion becomes effectively non-Markovian. Here, we present a theory that provides the mean reaction time for a non-Markovian Gaussian random walker in a large confining volume in the presence of a spatially localized reaction rate or a gated target. Remarkably, in the weakly reactive regime, for strongly subdiffusive processes, our theory predicts that the deviation of the mean reaction time to the reaction controlled time displays a non-trivial scaling with the reactivity, which we identify analytically. This effect illustrates how the memory of past passages to the target influences the statistics of next-return times, to the difference of Markovian processes. The theory is developed in one and two dimensions and agrees with stochastic simulations. These results provide a refined understanding of how non-Markovian transport and local reactivity influence the kinetics of diffusion controlled reactions.
Second Primary Differentiated Thyroid Carcinoma in Adult Cancer Survivors: A SEER Database Analysis
Authors: Feng Jianhua , Wu Caixiu , Shen Fei , Cai Wensong , Xu Bo
Published: July 2024

Context

Adult cancer survivors are at a heightened risk for secondary primary differentiated thyroid carcinoma (2-DTC). The characteristics and outcomes of 2-DTC remain poorly understood.

Objective

We aimed to explore the characteristics and outcomes of 2-DTC.

Methods

We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2017). 2-DTC was divided into 25 subgroups based on prior primary malignancies (PPMs). Baseline characteristics were compared using the chi-square test. Multivariable logistic analysis was used to identified if PPMs were associated with aggressive DTC characteristics. DTC-specific and cancer-specific mortality were analyzed using a univariable and multivariable competing risk regression model.

Results

There were 138 555 1-DTC and 9253 2-DTC patients identified. 2-DTC patients were predominantly older, male, and White compared to first primary DTC (1-DTC) (all P < .05). In multivariable logistic regression analysis, only 4 types of PPMs were associated with higher rates of DTC aggressive characteristics, while 19 types exhibited lower rates (all P < .05). In multivariable competing risk analysis, 2-DTC showed no mortality risk in stages I (SHR: 1.16; 95% CI, 0.65-2.07) and II (SHR: 0.67; 95% CI, 0.45-1.01), but a protective role in stages III (SHR: 0.47; 95% CI, 0.27-0.83) and IV (SHR: 0.72; 95% CI, 0.52-0.99). Most PPMs that developed into 2-DTC had a lower risk of DTC-specific death than 1-DTC, but many PPMs had a higher risk of cancer-specific death.

Conclusion

Given the characteristics and outcomes of 2-DTC, aggressive treatment for 2-DTC, particularly for PPM with a high mortality risk, may not be advisable.
Liraglutide Impacts Iron Homeostasis in a Murine Model of Hereditary Hemochromatosis
Authors: Bozadjieva-Kramer Nadejda , Shin Jae Hoon , Blok Neil B , Jain Chesta , Das Nupur K , Polex-Wolf Joseph , Knudsen Lotte Bjerre , Shah Yatrik M , Seeley Randy J
Published: July 2024

Classic hereditary hemochromatosis (HH) is an autosomal recessive iron-overload disorder resulting from loss-of-function mutations of the HFE gene. Patients with HH exhibit excessive hepatic iron accumulation that predisposes these patients to liver disease, including the risk for developing liver cancer. Chronic iron overload also poses a risk for the development of metabolic disorders such as obesity, type 2 diabetes, and insulin resistance. We hypothesized that liraglutide, GLP1 receptor agonist, alters iron metabolism while also reducing body weight and glucose tolerance in a mouse model of HH (global HFE knockout, HFE KO) and diet-induced obesity and glucose intolerance. The total body HFE KO and wild-type control mice were fed high-fat diet for 8 weeks. Mice were subdivided into liraglutide and vehicle-treated groups and received daily subcutaneous administration of the respective treatment once daily for 18 weeks. Liraglutide improved glucose tolerance and hepatic lipid markers and reduced body weight in a mouse model of HH, the HFE KO mouse, similar to wild-type controls. Importantly, our data show that liraglutide alters iron metabolism in HFE KO mice, leading to decreased circulating and stored iron levels in HFE KO mice. These observations highlight the potential that GLP1 receptor agonist could be used to reduce iron overload in addition to reducing body weight and improving glucose regulation in HH patients.
Thyroid Hormone Receptors in Control of Heart Rate
Authors: Dore Riccardo , Mittag Jens
Published: July 2024

Thyroid hormone has profound effects on cardiovascular functions, including heart rate. These effects can be mediated directly, for example, by changing the expression of target genes in the heart through nuclear thyroid hormone receptors, or indirectly by altering the autonomic nervous systems output of the brain. The underlying molecular mechanisms as well as the cellular substrates, however, are far from being understood. In this review, we summarize the recent key findings on the individual contributions of the two thyroid hormone receptor isoforms on the regulation of heart rate, challenging the role of the pacemaker channel genes Hcn2 and Hcn4 as sole mediators of the hormone's effect. Furthermore, we discuss the possible actions of thyroid hormone on the autonomic nervous system affecting heart rate distribution, and highlight the possibility of permanent alterations in heart and brain by impaired thyroid hormone action during development as important factors to consider when analyzing or designing experiments.
Woodhouse-Sakati Syndrome: The New Genetic Variant of DCAF17 In 2 Adult Sisters
Authors: Amosova Maria , Poluboyarinova Irina , Fadeev Valentin , Asanov Aliy
Published: July 2024

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder associated with progressive extrapyramidal signs, mental retardation, alopecia, and a variety of endocrine deficiencies, including diabetes mellitus, hypogonadism, and hypothyroidism. To date, approximately 98 genetically confirmed WSS families have been reported worldwide. This report focuses on a new genetic variant detected in 2 WSS-affected sisters with distinctive phenotypical features. The case under review is of special interest due to the multiple manifestations of WSS. This is the first family case of WSS identified in the Russian Federation. Although there is no specific treatment for WSS, genetic testing makes it possible to diagnose WSS, make a prognosis, and provide comprehensive patient-oriented treatment.
Neonatal Graves Disease Masquerading as Hemochromatosis
Authors: Maggiotto Liesbeth , Mittelman Steven D , Fallah Roja
Published: July 2024

Thyroid autoimmunity is extremely common in the adult population and can affect pregnancy outcomes. Signs in the newborn can range from absent to severe, making the diagnosis easy to miss. We present an interesting case of neonatal Graves disease associated with intrauterine growth restriction, premature delivery, and liver failure with severely high ferritin, thought to be secondary to hemochromatosis. Treatment of the underlying hyperthyroidism caused a rapid resolution of the elevated ferritin and liver failure. This report highlights the importance of considering Graves disease in newborns with liver failure of unknown etiology.
Syngeneic mouse model of YES-driven metastatic and proliferative hepatocellular carcinoma
Authors: Voisin Laure , Lapouge Marjorie , Saba-El-Leil Marc K. , Gombos Melania , Javary Joaquim , Trinh Vincent Q. , Meloche Sylvain
Published: July 2024

Hepatocellular carcinoma (HCC) is a disease of high unmet medical need that has become a global health problem. The development of targeted therapies for HCC has been hindered by the incomplete understanding of HCC pathogenesis and the limited number of relevant preclinical animal models. We recently unveiled a previously uncharacterized YES kinase (encoded by YES1)-dependent oncogenic signaling pathway in HCC. To model this subset of HCC, we established a series of syngeneic cell lines from liver tumors of transgenic mice expressing activated human YES. The resulting cell lines (referred to as HepYF) were enriched for expression of stem cell and progenitor markers, proliferated rapidly, and were characterized by high SRC family kinase (SFK) activity and activated mitogenic signaling pathways. Transcriptomic analysis indicated that HepYF cells are representative of the most aggressive proliferation class G3 subgroup of HCC. HepYF cells formed rapidly growing metastatic tumors upon orthotopic implantation into syngeneic hosts. Treatment with sorafenib or the SFK inhibitor dasatinib markedly inhibited the growth of HepYF tumors. The new HepYF HCC cell lines provide relevant preclinical models to study the pathogenesis of HCC and test novel small-molecule inhibitor and immunotherapy approaches.
Expansion microscopy reveals characteristic ultrastructural features of pathogenic budding yeast species
Authors: Reza Md Hashim , Dutta Srijana , Goyal Rohit , Shah Hiral , Dey Gautam , Sanyal Kaustuv
Published: July 2024

Candida albicans is the most prevalent fungal pathogen associated with candidemia. Similar to other fungi, the complex life cycle of C. albicans has been challenging to study with high-resolution microscopy due to its small size. Here, we employed ultrastructure expansion microscopy (U-ExM) to directly visualise subcellular structures at high resolution in the yeast and during its transition to hyphal growth. N-hydroxysuccinimide (NHS)-ester pan-labelling in combination with immunofluorescence via snapshots of various mitotic stages provided a comprehensive map of nucleolar and mitochondrial segregation dynamics and enabled the resolution of the inner and outer plaque of spindle pole bodies (SPBs). Analyses of microtubules (MTs) and SPBs suggest that C. albicans displays a side-by-side SPB arrangement with a short mitotic spindle and longer astral MTs (aMTs) at the pre-anaphase stage. Modifications to the established U-ExM protocol enabled the expansion of six other human fungal pathogens, revealing that the side-by-side SPB configuration is a plausibly conserved feature shared by many fungal species. We highlight the power of U-ExM to investigate subcellular organisation at high resolution and low cost in poorly studied and medically relevant microbial pathogens.
Case Report: Modified endoscopic hook for extracting magnetic esophageal foreign bodies in a rural area
Authors: Kadriyan Hamsu , Primayanti Ika , Syamsidar Syamsidar , Fakhrussiam Lalu Fauzan , Rozi Moh Fahrur , Hijrinelly Hijrinelly
Published: July 2024

Foreign bodies (FB) in the aerodigestive tract are common, especially in children. The type of foreign body in the esophagus can vary and include magnets. A magnet that lodges in the esophagus should be extracted within 24 hours to prevent complications due to associated chemical reactions. In rural areas, there are several limitations to extracting FBs from the esophagus. We report a case of a magnetic FB that lodged in the esophagus of a three-year-old boy. The extraction was successfully done by esophagoscopy with the modification of a hook that was attached to the endoscope. This innovation may help physician all over the world, especially in rural areas. In the future, this innovation could be produced on an industrial scale.
Designing Health Center Self-Measured Blood Pressure Program Models to Improve Hypertension Control
Authors: Smith Alison P. , Wagner Ashley L. , Harrison Nekeisha , Pillai Srijanani , Harmon Gary , Sanchez Eduardo
Published: July 2024

Summary: With the aim of achieving higher, equitable hypertension control rates, 350 nationwide federally qualified health centers implemented self-measured blood pressure programs (SMBP) over a three-year grant initiative. Various SMBP program designs with systematic processes, team-based care models, and culturally sensitive approaches with improved BP control are highlighted.
Affirming Community Cultural Wealth of Chicana/o and Latina/o Youth in a Community-Based After-School Program
Authors: Hernández Rafael J. C. , Nuñez-Alvarez Arcela , Ardón Ana María , Romero Gonzalez Rosalva A.
Published: July 2024

Summary: Racialized, deficit-oriented educational practices and inadequate safe spaces for youth undermine Communities of Color. We discuss our after-school program's framework, strategies, activities, and partnerships with community stakeholders, demonstrating that a collaborative, culturally responsive, strengths-based approach to mitigate trauma and enhance health and educational opportunities is essential for empowering Chicana/o/Latina/o youth and families.
Asymmetric demodulation using decision trees in gridless WDM systems
Authors: Martinez Zapata Kevin D. , Granada Torres Jhon J.
Published: July 2024

Different distortions that affect gridless wavelength division multiplexing (WDM) systems due to nonlinear impairments of the optical fiber and linear interchannel interference (ICI) errors cause signal degradation and a decrease in the transmission system quality. Overcoming these effects is a challenge if there is no information about the source of the distortion. In this work, we propose two asymmetric demodulation methods based on decision tree (DT) algorithms to mitigate distortions associated with linear ICI in gridless WDM systems, even when optical channels are spectrally overlapped. The first method uses the conventional DT and random forest (RDF) algorithms adapted to create asymmetrical thresholds in m-QAM digital demodulation. The second method uses the density-based spatial clustering of applications with a noise (DBSCAN) algorithm, including the K-Dimensional tree (K-D tree) algorithm to treat symbols in boundary conditions. Both methods were experimentally validated in a 3×16GBd gridless Nyquist WDM system modulated in 16-QAM with different channel spacing. DT-based demodulation, including RDF, achieved gains up to ∼1.6dB in the FEC limit 3.8×10−3, while demodulation based on DBSCAN plus the K-D tree achieved gains up to ∼1.2dB compared to conventional demodulation. Additionally, we performed a brief latency analysis in comparison to other previous machine learning-based demodulation methods, where DT and RDF presented latency up to ∼0.3% and ∼32% of the DBSCAN + K-D tree latency, respectively. Finally, the proposed asymmetric demodulation methods can improve the performance of future elastic optical networks by offering easy interpretation of the digital demodulation process and the possibility of adapting them to any m-QAM modulation format being agnostic to signal distortion.