bluuebunny/crossref_metadata_2025_split huggingface dataset:
A time-motion study of community health workers delivering community-based primary health care in Neno District, Malawi
Authors: Aron Moses Banda , Ndambo Myness Kasanda , Munyaneza Fabien , Mulwafu Manuel , Makungwa Henry , Nhlema Basimenye , Connolly Emilia 
Published: June 2023

Abstract
Introduction
Community health workers (CHWs) are vital resources in delivering community-based primary health care, especially in low-and-middle-income countries (LMIC). However, few studies have investigated detailed time and task assessments of CHW's work. We conducted a time-motion study to evaluate CHWs' time on health conditions and specific tasks in Neno District, Malawi.

Methods
We conducted a descriptive quantitative study utilizing a time observation tracker to capture time spent by CHWs on focused health conditions and tasks performed during household visits. We observed 64 CHWs between 29 June and 20 August 2020. We computed counts and median to describe CHW distribution, visit type, and time spent per health condition and task. We utilized Mood’s median test to compare the median time spent at a household during monthly visits with the program design standard time. We used pairwise median test to test differences in median time duration for health conditions and assigned tasks.

Results
We observed 660 CHW visits from 64 CHWs, with 95.2% (n = 628) of the visits as monthly household visits. The median time for a monthly household visit was 34 min, statistically less than the program design time of 60 min (p < 0.001). While the CHW program focused on eight disease areas, pretesting with the observation tool showed that CHWs were engaged in additional health areas like COVID-19. Of the 3043 health area touches by CHWs observed, COVID-19, tuberculosis, and non-communicable diseases (NCDs) had the highest touches (19.3%, 17.6%, and 16.6%, respectively). The median time spent on sexually transmitted infections (STIs) and NCDs was statistically higher than in other health areas (p < 0.05). Of 3813 tasks completed by CHWs, 1640 (43%) were on health education and promotion. A significant difference was observed in the median time spent on health education, promotion, and screening compared to other tasks (p < 0.05).

Conclusion
This study demonstrates that CHWs spend the most time on health education, promotion, and screening per programmatic objectives but, overall, less time than program design. CHWs deliver care for a broader range of health conditions than the programmatic design indicates. Future studies should examine associations between time spent and quality of care delivery.
Ambient RNAs removal of cortex-specific snRNA-seq reveals Apoe+ microglia/macrophage after deeper cerebral hypoperfusion in mice
Authors: Zhang Yuan , Tan Jinyun , Yang Kai , Fan Weijian , Yu Bo , Shi Weihao 
Published: June 2023

Abstract
Background
Ambient RNAs contamination in single-nuclei RNA sequencing (snRNA-seq) is a challenging problem, but the consequences of ambient RNAs contamination of damaged and/or diseased tissues are poorly understood. Cognitive impairments and white/gray matter injuries are characteristic of deeper cerebral hypoperfusion mouse models induced by bilateral carotid artery stenosis (BCAS), but the molecular mechanisms still need to be further explored. More importantly, the BCAS mice can also offer an excellent model to examine the signatures of ambient RNAs contamination in damaged tissues when performing snRNA-seq.

Methods
After the sham and BCAS mice were established, cortex-specific single-nuclei libraries were constructed. Single-nuclei transcriptomes were described informatically by the R package Seurat, and ambient RNA markers of were identified in each library. Then, after removing ambient RNAs in each sample using the in silico approaches, the combination of CellBender and subcluster cleaning, single-nuclei transcriptomes were reconstructed. Next, the comparison of ambient RNA contamination was performed using irGSEA analysis before and after the in silico approaches. Finally, further bioinformatic analyses were performed.

Results
The ambient RNAs are more predominant in the BCAS group than the sham group. The contamination mainly originated from damaged neuronal nuclei, but could be reduced largely using the in silico approaches. The integrative analysis of cortex-specific snRNA-seq data and the published bulk transcriptome revealed that microglia and other immune cells were the primary effectors. In the sequential microglia/immune subgroups analysis, the subgroup of Apoe+ MG/Mac (microglia/macrophages) was identified. Interestingly, this subgroup mainly participated in the pathways of lipid metabolism, associated with the phagocytosis of cell debris.

Conclusions
Taken together, our current study unravels the features of ambient RNAs in snRNA-seq datasets under diseased conditions, and the in silico approaches can effectively eliminate the incorrected cell annotation and following misleading analysis. In the future, snRNA-seq data analysis should be carefully revisited, and ambient RNAs removal needs to be taken into consideration, especially for those diseased tissues. To our best knowledge, our study also offers the first cortex-specific snRNA-seq data of deeper cerebral hypoperfusion, which provides with novel therapeutic targets.
Preoperative chemoradiation-induced hematological toxicity and related vertebral dosimetry evaluations in patients with locally advanced gastric cancer: data from a phase III clinical trial
Authors: Wang Ji-jin , Shao Han , Zhang Li , Jing Ming , Xu Wen-jing , Sun Heng-wen , Zhou Zhi-wei , Zhang Yu-jing 
Published: June 2023

Abstract
Background
To explore the hematological toxicity (HT) induced by neoadjuvant chemoradiotherapy (nCRT) compared with neoadjuvant chemotherapy (nCT) and to identify the appropriate vertebral body (VB) dosimetric parameters for predicting HT in patients with locally advanced gastric cancer (GC).

Methods
In the phase III study, 302 patients with GC from an ongoing multi-center randomized clinical trial (NCT 01815853) were included. Patients from two major centers were grouped into training and external validation cohorts. The nCT group received three cycles of XELOX chemotherapy, while the nCRT received the same dose-reduced chemotherapy plus 45 Gy radiotherapy. The complete blood counts at baseline, during neoadjuvant treatment, and in the preoperative period were compared between the nCT and nCRT groups. The VB was retrospectively contoured and the dose-volume parameters were extracted in the nCRT group. Patients’ clinical characteristics, VB dosimetric parameters, and HTs were statistically analyzed. Instances of HT were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The receiver operating characteristic (ROC) curves were generated to identify the optimal cut-off points for dosimetric variables and verify the prediction efficiency of the dosimetric index in both training and external validation cohorts.

Results
In the training cohort, 27.4% Grade 3 + HTs were noted in the nCRT group and 16.2% in the nCT group (P = 0.042). A similar result was exhibited in the validation cohort, with 35.0% Grade 3 + HTs in the nCRT group and 13.2% in the nCT group (P = 0.025). The multivariate analysis of the training cohort revealed that V5 was associated with Grade 3 + leukopenia (P = 0.000), Grade 3 + thrombocytopenia (P = 0.001), and Grade 3 + total HTs (P = 0.042). The Spearman correlation analysis identified a significant correlation of V5 with the white blood cell nadir (P = 0.0001) and platelet nadir (P = 0.0002). The ROC curve identified the optimal cut-off points for V5 and showed that V5 < 88.75% could indicate a decreased risk of Grade 3 + leukopenia, thrombocytopenia, and total HTs in the training as well as the external validation cohorts.

Conclusions
Compared with nCT, nCRT could increase the risk of Grade 3 + HT in patients with locally advanced GC. Dose constraints of V5 < 88.75% in irradiated VB could reduce the incidence of Grade 3 + HT.
Rewiring innate and adaptive immunity with TLR9 agonist to treat osteosarcoma
Authors: Cascini Caterina , Ratti Chiara , Botti Laura , Parma Beatrice , Cancila Valeria , Salvaggio Adriana , Meazza Cristina , Tripodo Claudio , Colombo Mario P. , Chiodoni Claudia 
Published: June 2023

Abstract
Background
Osteosarcoma (OS) is the most common primary bone tumor in children and adolescent. Surgery and multidrug chemotherapy are the standard of treatment achieving 60–70% of event-free survival for localized disease at diagnosis. However, for metastatic disease, the prognosis is dismal. Exploiting immune system activation in the setting of such unfavorable mesenchymal tumors represents a new therapeutic challenge.

Methods
In immune competent OS mouse models bearing two contralateral lesions, we tested the efficacy of intralesional administration of a TLR9 agonist against the treated and not treated contralateral lesion evaluating abscopal effect. Multiparametric flow cytometry was used to evaluate changes of the tumor immune microenviroment. Experiments in immune-deficient mice allowed the investigation of the role of adaptive T cells in TLR9 agonist effects, while T cell receptor sequencing was used to assess the expansion of specific T cell clones.

Results
TLR9 agonist strongly impaired the growth of locally-treated tumors and its therapeutic effect also extended to the contralateral, untreated lesion. Multiparametric flow cytometry showed conspicuous changes in the immune landscape of the OS immune microenvironment upon TLR9 engagement, involving a reduction in M2-like macrophages, paralleled by increased infiltration of dendritic cells and activated CD8 T cells in both lesions. Remarkably, CD8 T cells were needed for the induction of the abscopal effect, whereas they were not strictly necessary for halting the growth of the treated lesion. T cell receptor (TCR) sequencing of tumor infiltrating CD8 T cells showed the expansion of specific TCR clones in the treated tumors and, remarkably, their selected representation in the contralateral untreated lesions, providing the first evidence of the rewiring of tumor-associated T cell clonal architectures.

Conclusions
Overall these data indicate that the TLR9 agonist acts as an in situ anti-tumor vaccine, activating an innate immune response sufficient to suppress local tumor growth while inducing a systemic adaptive immunity with selective expansion of CD8 T cell clones, which are needed for the abscopal effect.

Graphical Abstract
Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial
Authors: Zarrabi Morteza , Shahrbaf Mohammad Amin , Nouri Masoumeh , Shekari Faezeh , Hosseini Seyedeh-Esmat , Hashemian Seyed-Mohammad Reza , Aliannejad Rasoul , Jamaati Hamidreza , Khavandgar Naghmeh , Alemi Hediyeh , Madani Hoda , Nazari Abdoreza , Amini Azadeh , Hassani Seyedeh Nafiseh , Abbasi Fatemeh , Jarooghi Neda , Fallah Nasrin , Taghiyar Leila , Ganjibakhsh Meysam , Hajizadeh-Saffar Ensiyeh , Vosough Massoud , Baharvand Hossein 
Published: June 2023

AbstractBackground and aimsThe main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients.Materials and methodsCOVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106cells) or one dose of MSCs (100 × 106cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention.ResultsA total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14–1.11;P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005–1.26;P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041).ConclusionMSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events.Trial registrationIRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020,http://www.irct.ir/trial/47073.
The microbiota of pregnant women with SARS-CoV-2 and their infants
Authors: Leftwich Heidi K. , Vargas-Robles Daniela , Rojas-Correa Mayra , Yap Yan Rou , Bhattarai Shakti , Ward Doyle V. , Fujimori Gavin , Forconi Catherine S. , Yeboah Tracy , Carter Acara , Kastrinakis Alyssa , Asirwatham Alison M. , Bucci Vanni , Moormann Ann M. , Maldonado-Contreras Ana 
Published: June 2023

AbstractBackgroundInfants receive their first bacteria from their birthing parent. This newly acquired microbiome plays a pivotal role in developing a robust immune system, the cornerstone of long-term health.ResultsWe demonstrated that the gut, vaginal, and oral microbial diversity of pregnant women with SARS-CoV-2 infection is reduced, and women with early infections exhibit a different vaginal microbiota composition at the time of delivery compared to their healthy control counterparts. Accordingly, a low relative abundance of twoStreptococcussequence variants (SV) was predictive of infants born to pregnant women with SARS-CoV-2 infection.ConclusionsOur data suggest that SARS-CoV-2 infections during pregnancy, particularly early infections, are associated with lasting changes in the microbiome of pregnant women, compromising the initial microbial seed of their infant. Our results highlight the importance of further exploring the impact of SARS-CoV-2 on the infant’s microbiome-dependent immune programming.
Properties of multi-GNSS uncalibrated phase delays with considering satellite systems, receiver types, and network scales
Authors: Zeng Ping , Zhang Zhetao , Wen Yuanlan , He Xiufeng , He Lina , Li Muzi , Chen Wu 
Published: June 2023

AbstractThe Wide-Lane (WL) and Narrow-Lane (NL) Uncalibrated Phase Delays (UPDs) are the prerequisites in the traditional Precise Point Positioning (PPP) Ambiguity Resolution (AR). As the generation mechanism of various biases becomes more complex, we systematically studied the impact factors of four satellite systems WL and NL UPDs from the perspective of parameter estimation. Approximately 100 stations in a global network are used to generate the UPDs. The results of different satellite systems show that the estimation method, update frequency, and solution mode need to be treated differently. Two regional networks with different receiver types, JAVAD, and Trimble, are also adopted. The results indicate that the receiver-dependent bias has an influence on UPD estimation. Also, the hardware delays can inhibit the satellite-side UPDs if these receiver-specific errors are not fully deployed or even misused. Furthermore, the temporal stability and residual distribution of NL UPDs are significantly enhanced by utilizing a regional network, with the improvements by over 68% and 40%, respectively. It demonstrates that different network scales exhibit the different implication of unmodeled errors, and the unmodeled errors cannot be ignored and must be handled in UPD estimation.
Using the Precision Lasso for gene selection in diffuse large B cell lymphoma cancer
Authors: Pourhamidi Rashed , Moslemi Azam 
Published: June 2023

Abstract
Background
Gene selection from gene expression profiles is the appropriate tool for diagnosing and predicting cancers. The aim of this study is to perform a Precision Lasso regression model on gene expression of diffuse large B cell lymphoma patients and to find marker genes related to DLBCL.

Methods
In the present case–control study, the dataset included 180 gene expressions from 14 healthy individuals and 17 DLBCL patients. The marker genes were selected by fitting Ridge, Lasso, Elastic Net, and Precision Lasso regression models.

Results
Based on our findings, the Precision Lasso, the Ridge, the Elastic Net, and the Lasso models choose the most marker genes, respectively. In addition, the top 20 genes are based on models compared with the results of clinical studies. The Precision Lasso and the Ridge models selected the most common genes with the clinical results, respectively.

Conclusions
The performance of the Precision Lasso model in selecting related genes could be considered more acceptable rather than other models.
Flexural behaviour of recycled reinforced concrete beams strengthened/ repaired with CFRP laminates
Authors: Hemida Ola Adel Ramadan , Abdalla Hany Ahmed , Fouad Hala Emad Elden 
Published: June 2023

AbstractThis research deals with the flexural performance of reinforced concrete beams which contain Recycled Concrete Aggregates (RCA) and were strengthened by Carbon Fiber Reinforced Polymers (CFRP). For this purpose, seven Reinforced Concrete (RC) beams were manufactured using RCA as a replacement of Normal Coarse aggregates (NCA) with percentages of (0%, 25%, 50%, and 100%). The cross-section of all beams was 150 × 300 mm and 2100 mm overall length and with loaded span of 1800 mm. Firstly four beams (group A) with different RCA ratios were loaded in a four-point loading configuration until failure. Secondly three beams (group B) were loaded to 30% of its ultimate load after that group B beams were strengthened using CFRP laminates on the lower face of the beams to be strengthened to resist flexural stress. Crack pattern, initial cracking load, ultimate load, mid-span deflection, and strain in main reinforcement were monitored. The results show that increasing RCA ratios generally leads to decreasing in the ultimate loads, for RCA ratios of 25%, 50% and 100% the decrease in beams ultimate load was with ratios 4.8%, 25.5% and 26.8%, respectively compared to control beam (0% RCA). The preloaded beams that were repaired with CFRP laminates have higher ultimate loads than beams without CFRP laminates and lower mid span deflection at maximum load (for instance repaired beam with 50% RCA ratio with CFRP laminate has shown higher ultimate load with 56.6% and less deflection with 36.9% compared to its corresponding unstrengthen beam).
SLKNet: An attention-based deep-learning framework for downhole distributed acoustic sensing data denoising
Authors: Yang Liuqing , Fomel Sergey , Wang Shoudong , Chen Xiaohong , Chen Yunfeng , Chen Yangkang 
Published: June 2023

Distributed acoustic sensing (DAS) is a novel and fast-developing seismic acquisition technology, which enjoys many advantages compared with traditional geophones. However, DAS data often suffer from severe and diverse types of noise with varying amplitudes, resulting in a low signal-to-noise ratio (S/N) and making the extraction of hidden signals a challenging task. Therefore, exploring a high-efficiency and high-generalization denoising method is crucial for improving the S/N of DAS data and subsequent processing. We develop a dense connection network with the kernel-wise attention mechanism to denoise complex and diverse noise (e.g., high-amplitude erratic, high-frequency, random, and horizontal noise) on real DAS data sets. We use an integrated denoising framework that is suitable for attenuating DAS noise to generate labels for network training. Our network consists of five types of blocks, i.e., convolutional, dense, transition down, transition up, and selective kernel blocks (SKB). In particular, the SKB is used to fuse multiscale features by weighting, thereby improving denoising accuracy. The computational efficiency and denoising performance are further augmented by using a patching method to segment the DAS data and generate many small-scale patches. Our network is trained on a small DAS data set and tested on the synthetic and field data from vastly different geographic areas. The comparisons of our network with three state-of-the-art deep-learning-based benchmark models demonstrate more robust performance and superior signal extraction ability.
Receptor-Based Pharmacophore Modelling of a series of ligands used as inhibitors of the SARS-CoV-2 virus by complementary theoretical approaches, molecular docking, and reactivity descriptors.
Authors: Morales-Bayuelo Alejandro , Sánchez-Márquez Jesús 
Published: June 2023

Background: A coronavirus identified in 2019, SARS-CoV-2, has caused a pandemic of respiratory illness, called COVID-19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: the Zidovudine, Tromantadine, Pyramidine, Oseltamivir, Hydroxychoroquine, Cobicistat, Doravirine (Pifeltro), Dolutegravir, Boceprevir, Indinavir, Truvada, Trizivir, Trifluridine, Sofosbuvir and Zalcitabine. Methods: These ligands were analyzed using molecular docking, Receptor-Based Pharmacophore Modelling. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LEU141, GLN189, GLU166 and GLY143, HIE41, among others. Also was development an electrostatic potential comparison using the global and local reactivity indices. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.