bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lactiplantibacillus plantarum, lactiplantibacillus pentosus and inulin meal inclusion boost the metagenomic function of broiler chickens
Authors: Ferrocino Ilario , Biasato Ilaria , Dabbou Sihem , Colombino Elena , Rantsiou Kalliopi , Squara Simone , Gariglio Marta , Capucchio Maria Teresa , Gasco Laura , Cordero Chiara Emilia , Liberto Erica , Schiavone Achille , Cocolin Luca 
Published: August 2023

Abstract
Background
The inclusion of alternative ingredients in poultry feed is foreseen to impact poultry gut microbiota. New feeding strategies (probiotics/prebiotics) must be adopted to allow sustainable productions. Therefore, the current study aimed to use metagenomics approaches to determine how dietary inclusion of prebiotic (inulin) plus a multi-strain probiotic mixture of Lactiplantibacillus plantarum and Lactiplantibacillus pentosus affected microbiota composition and functions of the gastro-intestinal tract of the broilers during production. Fecal samples were collected at the beginning of the trial and after 5, 11 and 32 days for metataxonomic analysis. At the end of the trial, broilers were submitted to anatomo-pathological investigations and caecal content was subjected to volatilome analysis and DNAseq.

Results
Probiotic plus prebiotic inclusion did not significantly influence bird performance and did not produce histopathological alterations or changes in blood measurements, which indicates that the probiotic did not impair the overall health status of the birds. The multi-strain probiotic plus inulin inclusion in broilers increased the abundance of Blautia, Faecalibacterium and Lachnospiraceae and as a consequence an increased level of butyric acid was observed. In addition, the administration of probiotics plus inulin modified the gut microbiota composition also at strain level since probiotics alone or in combination with inulin select specific Faecalibacterium prausnitzi strain populations. The metagenomic analysis showed in probiotic plus prebiotic fed broilers a higher number of genes required for branched-chain amino acid biosynthesis belonging to selected F. prausnitzi strains, which are crucial in increasing immune function resistance to pathogens. In the presence of the probiotic/prebiotic a reduction in the occurrence of antibiotic resistance genes belonging to aminoglycoside, beta-lactamase and lincosamide family was observed.

Conclusions
The positive microbiome modulation observed is particularly relevant, since the use of these alternative ingredients could promote a healthier status of the broiler’s gut.
Crystal structures of main protease (Mpro) mutants of SARS-CoV-2 variants bound to PF-07304814
Authors: Jiang Haihai , Zou Xiaofang , Zeng Pei , Zeng Xiangyi , Zhou Xuelan , Wang Jie , Zhang Jin , Li Jian 
Published: August 2023

AbstractThere is an urgent need to develop effective antiviral drugs to prevent the viral infection caused by constantly circulating SARS-CoV-2 as well as its variants. The main protease (Mpro) of SARS-CoV-2 is a salient enzyme that plays a vital role in viral replication and serves as a fascinating therapeutic target. PF-07304814 is a covalent inhibitor targeting SARS-CoV-2 Mpro with favorable inhibition potency and drug-like properties, thus making it a promising drug candidate for the treatment of COVID-19. We previously solved the structure of PF-07304814 in complex with SARS-CoV-2 Mpro. However, the binding modes of PF-07304814 with Mpros from evolving SARS-CoV-2 variants is under-determined. In the current study, we expressed six Mpro mutants (G15S, K90R, M49I, S46F, V186F, and Y54C) that have been identified in Omicron variants including the recently emerged XBB.1.16 subvariant and solved the crystal structures of PF-07304814 bound to Mpro mutants. Structural analysis provided insight into the key molecular determinants responsible for the interaction between PF-07304814 and these mutant Mpros. Patterns for PF-07304814 to bind with these investigated Mpro mutants and the wild-type Mpro are generally similar but with some differences as revealed by detailed structural comparison. Structural insights presented in this study will inform the development of novel drugs against SARS-CoV-2 and the possible conformation changes of Mpro mutants when bound to an inhibitor.
Simultaneous waveform inversion of seismic-while-drilling data for P-wave velocity, density, and source parameters
Authors: Li Jinji , Keating Scott D. , Innanen Kristopher A. , Shor Roman , Kazemi Nasser 
Published: August 2023

Full-waveform inversion (FWI), as an optimization-based approach to estimating subsurface models, is limited by incomplete acquisition and illumination of the subsurface. The incorporation of additional data from new and independent raypaths should be expected to result in significant increase in the accuracy of FWI models. In principle, seismic-while-drilling (SWD) technology can supply these additional raypaths; however, it introduces a new suite of unknowns, namely precise source locations (i.e., drilling path), source signature, and radiation characteristics. A new FWI algorithm is formulated in which the source radiation patterns and positions join the velocity and density values of the grid cells as unknowns to be determined. Several numerical inversion experiments are then conducted with different source settings using a synthetic model. The SWD sources are supplemented by explosive sources and multicomponent receivers at the surface, simulating a conventional surface acquisition geometry. The subsurface model and SWD source properties are recovered and analyzed. The analysis is suggestive that SWD involvement can enhance the accuracy of FWI models, with varying degrees of enhancement depending on factors such as trajectory inclination, source density, and drill path extension. The impact of SWD-FWI over standard FWI is reduced when low-frequency data are missing, but improvements over the models constructed with no subsurface sources remain. This formulation permits general source information, such as position and moment tensor components, to be independently obtained. This inversion scheme may lead to a range of potential applications for which medium properties and source information are required.
Creating a cancer advocacy program in Indonesia.
Authors: Lee David Dai-Wee , Tane Kaori , Permata Tiara Bunga Mayang , Su Yu-Li , Malik Monica , Stockler Martin R. ,   ASCO Leadership Development Program Asia Pacific 2021 - 2022
Published: August 2023

105 Background: Political will is crucial for successful cancer control. The ASCO Asia-Pacific Leadership Development Program tasked our group to address this issue. We identified the development of cancer advocacy in the Asia-Pacific as a key enabler, and Indonesia as ideal to develop and pilot a generalisable program. Indonesia has 270M citizens spread over 17,000 islands and 38 provinces posing major challenges for cancer control. There are no established cancer advocacy platforms in Indonesia with limited advocacy knowledge and readiness in the oncology community. Methods: Our vision is to establish a sustainable home for cancer control networks, with wide outreach throughout Indonesia. Our missions are to bridge the gap between cancer experts, patients, and policy makers; establish a network of cancer control platforms widely reaching to local districts, and empower cancer advocacy. This project proposes 2 main objectives. Firstly to cultivate cancer advocacy with a two-tier approach. We plan to collaborate with ASCO advocacy experts to develop a curriculum for cancer advocacy training, which would be conducted at an Indonesian cancer society meeting for oncologists. Thereafter, to create a web-based on-demand advocacy training for the wider community including nurses, patients, carers, and others using interactive e-learning activities. The second objective is to set up provincial cancer control platforms. These will be established by oncologists who have completed cancer advocacy training, to reach out to their local stakeholders. These provincial platforms will identify local cancer care gaps, and develop strategies to improve cancer control locally. The target is for these groups to hold at least one cancer awareness activity each year. At the national level, we plan to hold annual national cancer forums focusing on cancer advocacy, to congregate local advocacy champions and policy makers. This meeting will help cancer experts, advocates, and other stakeholders to meet with decision makers. Results: We plan for at least one oncologist from each Indonesian province to attend the advocacy training program in the first year. This will be expanded in the second year to include at least 2 participants per province in the on-demand cancer advocacy program. The national cancer control forum is planned for year 2. Conclusions: We aspire to build a sustainable, provincial training program for cancer advocacy, and to develop provincial cancer control networks in Indonesia. Once implemented, this model can be modified for application in other Asia Pacific countries.
Heart rate variability and the quality of life of patients receiving chemotherapy against gynecologic malignancies.
Authors: Higashiyama Nozomi , Yamaguchi Ken , Inayama Yoshihide , Koike Ayami , Ueda Akihiko , Kitamura Sachiko , Taki Mana , Yamanoi Koji , Murakami Ryusuke , Egawa Miho , Hamanishi Junzo , Mandai Masaki 
Published: August 2023

106 Background: Improving quality of life (QOL) of patients with cancer is essential. However, evaluating QOL requires completing QOL questionnaires consisting of 30–40 questions, which is too burdensome for the patients to continue. Therefore, development of the methodology which does not dependent on the adherence of the patients is urgent to evaluate QOL. Recently, heart rate variability (HRV) has been reported to be associated with the autonomic nervous system. This study aims to develop and validate a machine-learning model to predict QOL from HRV. Methods: Fifty patients with gynecological cancers from our hospital were used as test data, and 15 patients with gynecological cancer from other hospitals were used as validation data. Using a mobile application, they recorded daily HRV and weekly QOL questionnaires (EORTC qlq-C30, FACT-G, PHQ9, PRO-CTCAE). A binary classification model was developed using the XgBoost Classifier to predict whether patients experienced at least one of severe numbness, insomnia, depression, and fatigue using their HRV. SHAP values of the HRV used for prediction were clustered into three groups using unsupervised learning (Parametric Umap). QOL indices for each group were compared. Metabolites in serums that contribute to HRV variation were identified using metabolome analysis. Results: Clustering using the SHAP values indicated high, middle, and low QOL groups (Group A, B, and C, respectively). The total score of FACT-G, an index of overall QOL, was 82.4, 72.7, and 67.3 out of 108 (Group A, B, and C, respectively). Global health status, another index of overall QOL was also highest in Group A and lowest in Group C. The score of fatigue was 27.2, 46.3, and 54.9 out of 100; the score of pain was 17.6, 27.2, and 35.8 out of 100; the score of depression was 1.8, 4.5, and 6.6 out of 27 (Group A, B, and C, respectively). The scores of numbness, diarrhea, appetite loss, insomnia and nausea were also highest in the Group C and lowest in the Group A. The HRV of validation datasets also showed a similar classification with total scores of FACT-G as 76.0, 67.8, and 62.1 and the score of depression as 3.8, 5.7 and 8.0 (Group A, B, and C, respectively). Metabolites in serum contributing to HRV variation are Arachidonic acid and Dopamine, which are associated with inflammation and depression. Conclusions: Measuring HRV is a simple way to evaluate the QOL of patients with gynecologic cancers. Monitoring QOL over time using HRV possibly allows early detection of deterioration in QOL, such as complications and side effects of chemotherapy. Clinical trial information: UMIN000038937 .
Improving treatment adherence in patients with cancer in low and middle-income countries, through digital health self-care interventions.
Authors: Akinjiola Kolawole , Ogboye Ayoposi 
Published: August 2023

114 Background: The WHO notes that adherence to treatment for people living with chronic conditions, including cancer is of global concern. This poor adherence is brought about in low- and middle-income countries like Nigeria, by patient factors such as poor health literacy, overshadowing religious beliefs, and forgetfulness, as well as systemic factors like fragmented patient care due to physician burnout. The aim of this study was to evaluate the effectiveness of digital self-care interventions via CompleteHealth in improving treatment adherence in people living with cancer. Methods: This was a retrospective study done on 63 patients on treatment for metastatic castrate-resistant prostate cancer, enrolled on mDoc’s digital CompleteHealth platform between January to December 2022. Each patient was assigned a virtual health coach who provided self-care support, monitored their health metrics, encouraged regular physical activity, and maintained normal body weight. Synchronous and asynchronous digital nudges were provided via the multiple channels of the digital CompleteHealth platform such as the web app, SMS, and phone calls. The patients also had access to virtual fitness, nutrition, and emotional wellness coaches as required. Results: 56/63 patients (88%) completed their full course of 6 months of treatment. The adherence was at 78.4%, which represents the average percentage of members who refilled medication as at when due, allowing for 30 days or less between fillings. Allowing for 90 days in between fillings, adherence was at 90.5%. Conclusions: The use of digital health interventions via virtual health coaching for self-care support has been demonstrated through CompleteHealth to improve treatment adherence in patients living with cancer significantly. There is therefore a place to scale up the use of digital health coaching to further improve this statistic, as it is likely to impact treatment outcomes positively.
VPAC targeted optical imaging assay (VPAC assay) of voided urine for management of patients with persistently elevated PSA.
Authors: Thakur Mathew L. , Trabulsi Edouard John , Dale Emma , Singh Vivek , Chhabra Anupriya , Dahlgren Olivia , Kolesnikov Oleksandr , Wang Kerith , Gomella Leonard G. 
Published: August 2023

124 Background: Nearly 50% of patients with persistently elevated PSA (PEP) have prostate cancer (PCa) despite previous negative biopsy. However not all patients agree to undergo repeat, invasive trans rectal or trans perineal prostate biopsy (PB). To identify men at high risk of PCa, the need is unmet of other reliable diagnostic methods. The goal of this investigation was to determine if the VPAC assay, which is being developed in our laboratory and detects PCa efficiently, by imaging PCa cells shed in voided urine, collected without digital rectal examination (DRE), can address the common clinical dilemma of when or if to repeat biopsy on PEP subjects. Methods: PEP patients (N=21, 55-75 yr. PSA 2.8 – 42 ng/ml), scheduled for PB and signed informed consent form were enrolled. They provided pre and clinically required, post DRE urine. VPAC assay was performed on both urine samples from each patient. VPAC, a genomic receptor, encodes G protein and expresses in high density on all malignant PCa cells, was targeted with TP4303, a biomolecule with fluorophore, designed in our laboratory with high affinity (Kd, 3.1x10-9M) for VPAC. Urine was centrifuged, cells on a glass slide fixed, incubated with TP4303 and excess was washed. Cells were then examined under a microscope. TP4303 fluorescence around cell nucleus allowed to identify malignant PCa cells. For urine collected post DRE, MDx Health assay, approved by FDA and determines mRNA levels of DXL1 and HOXC6 biomarkers and indicates risk of PCa, was also performed. Results were compared with gold standard histopathology of tissues acquired through PB, and evaluated statistically. Results: Of 21 PEP patients, who underwent PB, three (14%) had histopathologically proven, clinically significant PCa with Grade Group 2. All three (100%) patients were correctly identified as positive for PCa by the VPAC assay, while MDx reported low risk for two (9.5%) and high risk for one (53%). Of the remaining 18, histologically negative subjects, VPAC assay was disconcordant in five (28%), with positive for PCa. In these five patients, MDx also reported moderate to high risk (40%-59%). Of the remaining 13 histologically negative PCa patient, all (100%) had concordant results with VPAC assay while MDx reported low risk in 2 patients and moderate to high risk (range 30% to 90%) in other eleven. Results with sensitivity and specificity of the assays are given in the table. Conclusions: The VPAC assay data, in this small exploratory cohort, appear promising as an additional diagnostic in the clinical management of PEP patients, minimizing the number of unnecessary invasive PBs and eliminating possible overtreatment. Work is in progress. Support: NIH 5R01CA249921. [Table: see text]
The challenge of colorectal cancer (CRC) screening in low and middle-income countries (LMIC): The Brazilian ten year long experience.
Authors: Filogonio Victor , Maia Yara Rafaela , Maia Lucas Henrique 
Published: August 2023

129 Background: The increasing incidence of CRC seen in LMIC and the high mortality rates compared to high-income countries points towards the difficult implementation of an effective screening strategy in LMIC. Brazil is one of the few Latin American countries and LMIC that have a population-based CRC screening program, targeting ages 50 to 74 and performing a fecal occult blood test (FT) every 2 years and colonoscopy/sigmoidoscopy as a confirmatory test. Methods: We performed a cross-sectional study, which evaluated the prevalence of every stage of CRC/carcinoma in situ (CIS) at the time of its diagnosis from 2013 to 2022. Similar data regarding the Brazilian breast and cervical cancer screening programs was obtained. Each stage was evaluated by age targeted by their respective screening program using the national database (DATASUS). Results: In the analyzed decade there was a total of 87507 CRC/CIS cases in the overall studied population, which only 11% was of Stage I or less and 70% was of stage III or IV at the time of diagnosis. In the subdivided age groups, the prevalence of each stage remained somewhat constant through all groups (In situ/Stage 0 = 8-9%; Stage I = 3%; Stage II = 20-21%; Stage III = 35-36%; Stage IV = 32-34%) and the majority of cases occurred from age 60 to 64 (20549 cases). In 2022, a total of 2128168 RT was performed - corresponding to only 4,6% of the targeted population - and 408489 colonoscopies. When compared to other cancer screening programs, CRC presents indifferent to age group, sustaining constant rate of regional/distant stages, with at least 32% of patients presenting a <17% 5-year survival rate (5-YSR), whereas cervical cancer presents approximately 80% of cases at >91% 5-YSR at the first age group, and breast cancer with 89% of cases at >86% 5-YSR at the first age group. Conclusions: Data suggests the inefficacy of CRC screening implementation, and literature sustains to be due to its poor acceptance by the population and the unavailability of confirmatory imaging tests due to long-waiting times and high cost, reducing its ability to detect early stage lesions, in contrast with the overall acceptance and high effectivity of cervical/breast cancer screening. The discrepancy between the guidelines and their implementation as a screening program in LMIC are in consonant. This study aims to be a launching point for new research and interventional studies evaluating the impact of better locally adjusted actions in the prevention of CRC such as screening invitations, in-community health education, and the developing of better cost-benefit confirmatory methods might hinder the advance of CRC in LMIC.[Table: see text]
Impact of cost of Oncotype DX versus CanAssist Breast, an Indian prognostic test, in the management of node-negative early breast cancer in a single centre in India.
Authors: Bapna Ajay , Samar Aseem Kumar , Gupta Tarachand , Agarwal Pawan 
Published: August 2023

14 Background: It is well known that prognostication is important as not all women benefit equally from adjuvant chemotherapy, especially in HR+/HER2- early breast cancer (BC). Multiple publications have showcased the cost-effectiveness of Oncotype DX (ODX) in various countries. However, ODX remains out of reach for many patients in under-resourced geographies like Asia, Africa etc where healthcare insurance is not a norm. CanAssist Breast (CAB) is an affordable prognostic test developed on Indian patients. CAB couples the immunohistochemistry technique with an AI/ML-based prediction model to segregate patients as either low-risk or high-risk for distant breast cancer recurrence. CAB has been validated in the USA, Spain, Germany, Austria, Italy, and The Netherlands for predicting 5–10-year distant recurrences and has comparable low-risk accuracy with that of ODX/MammaPrint. In this abstract, we present real-world data about cost-analysis of the use of CanAssist Breast versus ODX in a single cancer care centre in Rajasthan, a state in Western India that has a per capita income of $ 1504 as against $ 68,400 in the USA. Methods: 124 patients with node-negative early BC were treated at a trust hospital in Jaipur, Rajasthan from 2020-2022. All the high-risk patients received chemotherapy at the treating clinician’s discretion. For the cost analysis model, the cost of chemotherapy drugs, hospitalization charges, and costs involved in managing short-term adverse events was compared for CAB and ODX. Treatment is provided at subsidized costs to the patients in this trust hospital. Results: The median age of this cohort was 55 years (35-78), with primarily T2 and G2 diseases. High-risk proportions were 27% and 17% (as per TAILORx) and by CAB and ODX respectively. The cost of ODX is 5.8 times higher than the cost of CAB. The cost savings per patient with CAB over ODX were US $ 3477 (Rs. 278161) in this trust hospital. Conclusions: This economic model shows that the use of ODX could impose an economic burden due to its cost. Use of CAB would lead to savings without comprising the patient’s health, as both tests have comparable performance.