bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients
Authors: Canti Lorenzo , Humblet-Baron Stéphanie , Desombere Isabelle , Neumann Julika , Pannus Pieter , Heyndrickx Leo , Henry Aurélie , Servais Sophie , Willems Evelyne , Ehx Grégory , Goriely Stanislas , Seidel Laurence , Michiels Johan , Willems Betty , Liston Adrian , Ariën Kevin K. , Beguin Yves , Goossens Maria E. , Marchant Arnaud , Baron Frédéric 
Published: October 2021

Abstract
Background
Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated.

Methods
Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses.

Results
Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4+ T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01).

Conclusions
Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination.

Trial registration

The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).
The effect of opioids on gastrointestinal function in the ICU
Authors: Yan Yun , Chen Yu , Zhang Xijing 
Published: October 2021

AbstractGastrointestinal (GI) dysfunction is common in the critical care setting and is highly associated with clinical outcomes. Opioids increase the risk for GI dysfunction and are frequently prescribed to reduce pain in critically ill patients. However, the role of opioids in GI function remains uncertain in the ICU. This review aims to describe the effect of opioids on GI motility, their potential risk of increasing infection and the treatment of GI dysmotility with opioid antagonists in the ICU setting.
Clinical trial recruiters’ experiences working with trial eligibility criteria: results of an exploratory, cross-sectional, online survey in the UK
Authors: Cragg William J. , McMahon Kathryn , Oughton Jamie B. , Sigsworth Rachel , Taylor Christopher , Napp Vicky 
Published: October 2021

Abstract
Background
Eligibility criteria are a fundamental element of clinical trial design, defining who can and who should not participate in a trial. Problems with the design or application of criteria are known to occur and pose risks to participants’ safety and trial integrity, sometimes also negatively impacting on trial recruitment and generalisability. We conducted a short, exploratory survey to gather evidence on UK recruiters’ experiences interpreting and applying eligibility criteria and their views on how criteria are communicated and developed.

Methods
Our survey included topics informed by a wider programme of work at the Clinical Trials Research Unit, University of Leeds, on assuring eligibility criteria quality. Respondents were asked to answer based on all their trial experience, not only on experiences with our trials. The survey was disseminated to recruiters collaborating on trials run at our trials unit, and via other mailing lists and social media. The quantitative responses were descriptively analysed, with inductive analysis of free-text responses to identify themes.

Results
A total of 823 eligible respondents participated. In total, 79% of respondents reported finding problems with eligibility criteria in some trials, and 9% in most trials. The main themes in the types of problems experienced were criteria clarity (67% of comments), feasibility (34%), and suitability (14%). In total, 27% of those reporting some level of problem said these problems had led to patients being incorrectly included in trials; 40% said they had led to incorrect exclusions. Most respondents (56%) reported accessing eligibility criteria mainly in the trial protocol. Most respondents (74%) supported the idea of recruiter review of eligibility criteria earlier in the protocol development process.

Conclusions
Our survey corroborates other evidence about the existence of suboptimal trial eligibility criteria. Problems with clarity were the most often reported, but the number of comments on feasibility and suitability suggest some recruiters feel eligibility criteria and associated assessments can hinder recruitment to trials. Our proposal for more recruiter involvement in protocol development has strong support and some potential benefits, but questions remain about how best to implement this. We invite other trialists to consider our other suggestions for how to assure quality in trial eligibility criteria.
Endogenous CRISPR-assisted microhomology-mediated end joining enables rapid genome editing in Zymomonas mobilis
Authors: Sui Xin , Wang Xiaojie , Liu Tao , Ye Qing , Wu Bo , Hu Guoquan , Yang Shihui , He Mingxiong , Peng Nan 
Published: October 2021

Abstract
Background
Zymomonas mobilis is a natural ethanologen with many desirable characteristics, making it an ideal platform for future biorefineries. Recently, an endogenous CRISPR-based genome editing tool has been developed for this species. However, a simple and high-efficient genome editing method is still required.

Results
We developed a novel gene deletion tool based on the endogenous subtype I–F CRISPR-Cas system and the microhomology-mediated end joining (MMEJ) pathway. This tool only requires a self-interference plasmid carrying the mini-CRISPR (Repeat–Spacer–Repeat) expression cassette, where the spacer matches the target DNA. Transformation of the self-interference plasmid leads to target DNA damage and subsequently triggers the endogenous MMEJ pathway to repair the damaged DNA, leaving deletions normally smaller than 500 bp. Importantly, the MMEJ repair efficiency was increased by introducing mutations at the second repeat of the mini-CRISPR cassette expressing the guide RNA. Several genes have been successfully deleted via this method, and the phenotype of a σ28 deletion mutant generated in this study was characterized. Moreover, large fragment deletions were obtained by transformation of the self-interference plasmids expressing two guide RNAs in tandem.

Conclusions
Here, we report the establishment of an efficient gene deletion tool based on the endogenous subtype I–F CRISPR-Cas system and the MMEJ pathway in Zymomonas mobilis. We achieved single gene deletion and large-fragment knockout using this tool. In addition, we further promoted the editing efficiency by modifying the guide RNA expression cassette and selecting lower GC% target sites. Our study has provided an effective method for genetic manipulation in Z. mobilis.
The acceptability of targeted mass treatment with primaquine for local elimination of vivax malaria in a northern Myanmar township: a mixed-methods study
Authors: Aung Pyae Linn , Soe Myat Thu , Soe Than Naing , Oo Thit Lwin , Aung Poh Poh , Khin Aung , Thi Aung , Phuanukoonnon Suparat , Okanurak Kamolnetr , Cui Liwang , Kyaw Myat Phone , Parker Daniel M. 
Published: October 2021

Abstract
Background
Radical cure of the Plasmodium vivax latent liver stage is required to effectively manage vivax malaria. Targeted mass treatment with primaquine may be an effective mechanism for reducing reservoirs of the disease. Since community engagement and high coverage are essential for mass treatment programs, this study aimed to determine the acceptability of mass primaquine treatment in a targeted community in a northern Myanmar township.

Methods
A cross-sectional mixed-methods study was deployed among household leaders in July 2019. Face-to-face interviews using structured questionnaires and standardized qualitative guidelines were conducted to gather information. Descriptive and inferential statistics, including logistic regression models, were applied.

Results
Among 609 study respondents, > 90% agreed to participate in an upcoming targeted mass primaquine treatment (TPT) program. Factors contributing to higher odds of acceptability of the program were older age [adjusted odds ratios (aOR): 2.38, 95% confidence intervals (CI) 1.08–8.96], secondary education level (aOR: 3.99, 95% CI 1.12–20.01), having good knowledge of malaria (aOR: 2.12, 95% CI 1.04–4.76), experiencing malaria within the family (aOR: 1.92, 95% CI 1.14–5.13), and believing eliminating malaria from the village is possible (aOR: 2.83, 95% CI 1.07–4.07). Furthermore, 50 community respondents, 6 midwives, and 4 public health staff (grade II) participated in the qualitative component of the study. Many thought that TPT seemed feasible and stressed that high coverage of underserved groups and health education are needed before commencing the activity.

Conclusions
Most respondents agreed to participate in the proposed mass treatment campaign. Older people with secondary education level and those who had experienced malaria within their families were most likely to report willingness to participate. These same individuals may be important in the community engagement process to increase community acceptance of the program.

Graphical abstract
Ten-year follow-up of sitagliptin treatment in patients with type 2 diabetes mellitus
Authors: Hattori Sachiko 
Published: October 2021

Abstract
Background
Early and effective intervention with a dipeptidyl peptidase 4 inhibitor (DPP4i) before the development of advanced atherosclerosis in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease (CVD) is reported to increase the chance of significant reductions in not only microvascular disease, but also CVD.

Method
This study aimed to investigate whether sitagliptin is effective and tolerated for glycemic control and whether renoprotective effects and β-cell function are preserved for as long as ten years in Japanese patients with T2DM without a history of CVD.

Results
The situation is equivalent to improving glycemic control as assessed by hemoglobin A1c both in a sitagliptin group [sitagliptin 50 mg as either monotherapy or combination therapy with other oral glucose-lowering drugs (n = 17)] or a control group [placebo as either monotherapy or combination therapy with other glucose-lowering drugs (n = 9)], while anti-inflammatory effects as assessed by high-sensitivity C-reactive peptide in the sitagliptin group were superior to those in the control group. In the sitagliptin group, mean urinary albumin excretion (measured as urinary albumin-to-creatinine ratio) was markedly decreased, but no changes in estimated glomerular filtration rate were seen throughout the study. Beta-cell function as evaluated by homeostatic model assessment of β-cell function values was reduced at baseline in both groups, improved significantly in the sitagliptin group, and continued unchanged in the control group during the study.

Conclusion
These observations suggest that early intervention with sitagliptin in patients with T2DM may have long-lasting renoprotective and islet-protective effects.
Trial registration: UMIN Clinical Registry (UMIN000038459). Registered 01 November (retrospectively registered): https://upload.umin.ac.jp/UMIN000038459
A toolkit for haptic force feedback in a telerobotic ultrasound system
Authors: Fotouhi Reza , Najafi Semnani Atieh , Zhang QianWei , Adams Scott J. , Obaid Haron 
Published: October 2021

AbstractObjectiveTo develop a collision engine (haptic force feedback simulator) compatible with a 5-degrees-of-freedom (DOF) haptic wand. This has broad applications such as telerobotic ultrasound systems. Integrating force feedback into systems is critical to optimize remote scanning. A collision engine compatible with a 5-DOF haptic wand was developed based on the Gilbert–Johnson–Keerthi algorithm. The collision engine calculated force during collision between the wand and a virtual object based on code developed using MATLAB. A proportional force was subsequently returned to a user via the haptic wand, thereby simulating the collision force for the user. Three experiments were conducted to assess the accuracy of the collision engine on curved and flat surfaces.ResultsThe average errors in calculation of distances between the wand and virtual object were 2.1 cm, 3.4 cm, and 4.2 cm for the model of the human hand, cylinder, and cuboid, respectively. The collision engine accurately simulated forces on a flat surface, though was less accurate on curved surfaces. Future work will incorporate haptic force feedback into a telerobotic ultrasound system. The haptic force simulator presented here may also be used in the development of ultrasound simulators for training and education.
Cell-free DNA 5-hydroxymethylcytosine profiles of long non-coding RNA genes enable early detection and progression monitoring of human cancers
Authors: Zhou Meng , Hou Ping , Yan Congcong , Chen Lu , Li Ke , Wang Yiran , Zhao Jingting , Su Jianzhong , Sun Jie 
Published: October 2021

AbstractBackground5-Hydroxymethylcytosine (5hmC) is a significant DNA epigenetic modification. However, the 5hmC modification alterations in genomic regions encoding long non-coding RNA (lncRNA) and their clinical significance remain poorly characterized.ResultsA three-phase discovery–modeling–validation study was conducted to explore the potential of the plasma-derived 5hmC modification level in genomic regions encoding lncRNAs as a superior alternative biomarker for cancer diagnosis and surveillance. Genome-wide 5hmC profiles in the plasma circulating cell-free DNA of 1632 cancer and 1379 non-cancerous control samples from different cancer types and multiple centers were repurposed and characterized. A large number of altered 5hmC modifications were distributed at genomic regions encoding lncRNAs in cancerous compared with healthy subjects. Furthermore, most 5hmC-modified lncRNA genes were cancer-specific, with only a relatively small number of 5hmC-modified lncRNA genes shared by various cancer types. A 5hmC-LncRNA diagnostic score (5hLD-score) comprising 39 tissue-shared 5hmC-modified lncRNA gene markers was developed using elastic net regularization. The 5hLD-score was able to accurately distinguish tumors from healthy controls with an area under the curve (AUC) of 0.963 [95% confidence interval (CI) 0.940–0.985] and 0.912 (95% CI 0.837–0.987) in the training and internal validation cohorts, respectively. Results from three independent validations confirmed the robustness and stability of the 5hLD-score with an AUC of 0.851 (95% CI 0.786–0.916) in Zhang’s non-small cell lung cancer cohort, AUC of 0.887 (95% CI 0.852–0.922) in Tian’s esophageal cancer cohort, and AUC of 0.768 (95% CI 0.746–0.790) in Cai’s hepatocellular carcinoma cohort. In addition, a significant association was identified between the 5hLD-score and the progression from hepatitis to liver cancer. Finally, lncRNA genes modified by tissue-specific 5hmC alteration were again found to be capable of identifying the origin and location of tumors.ConclusionThe present study will contribute to the ongoing effort to understand the transcriptional programs of lncRNA genes, as well as facilitate the development of novel invasive genomic tools for early cancer detection and surveillance.
Cumulative evidence for association of rhinitis and depression
Authors: Wang Jing , Xiao Dongqiong , Chen Huayou , Hu Juan 
Published: October 2021

Abstract
Background
Several primary studies evaluated the association between rhinitis and the incidence of depression and yielded inconsistent results. We conducted a meta-analysis of studies evaluating the association between rhinitis and depression.

Methods
We searched the EMBASE, PubMed and Cochrane Library databases for studies published in English before April 1, 2019. The studies were included if they reported any type of rhinitis in relation to depression. Two authors independently extracted the data. The odds ratios (ORs) were pooled using a random-effects model. Stratified analyses were conducted to evaluate the association.

Results
Among the 3472 initially identified studies, we included 14 studies involving a total of 19.36 ± 1.1 million participants according to predefined inclusion criteria. The associations between rhinitis (R), allergic rhinitis (AR), and nonallergic rhinitis (NAR) and depression were significant with ORs of 1.86 (95% CI 1.32 to 2.62, p < 0.05), 1.54 (95% CI 1.24 to 1.90, p < 0.05), and 2.15 (95% CI 1.49 to 3.09, p < 0.05), respectively. The results were consistent and statistically significant in all subgroup analyses.

Conclusions
Rhinitis was associated with an increased risk of depression. Further prospective studies involving large sample sizes are required to confirm the results by considering more confounders and clarify the mechanisms.
Activation of the EGFR-PI3K-CaM pathway by PRL-1-overexpressing placenta-derived mesenchymal stem cells ameliorates liver cirrhosis via ER stress-dependent calcium
Authors: Kim Se Ho , Kim Jae Yeon , Park Soo Young , Jeong Won Tae , Kim Jin Man , Bae Si Hyun , Kim Gi Jin 
Published: October 2021

Abstract
Background
Cholesterol accumulation and calcium depletion induce hepatic injury via the endoplasmic reticulum (ER) stress response. ER stress regulates the calcium imbalance between the ER and mitochondria. We previously reported that phosphatase of regenerating liver-1 (PRL-1)-overexpressing placenta-derived mesenchymal stem cells (PD-MSCsPRL−1) promoted liver regeneration via mitochondrial dynamics in a cirrhotic rat model. However, the role of PRL-1 in ER stress-dependent calcium is not clear. Therefore, we demonstrated that PD-MSCsPRL−1 improved hepatic functions by regulating ER stress and calcium channels in a rat model of bile duct ligation (BDL).

Methods
Liver cirrhosis was induced in Sprague–Dawley (SD) rats using surgically induced BDL for 10 days. PD-MSCs and PD-MSCsPRL−1 (2 × 106 cells) were intravenously administered to animals, and their therapeutic effects were analyzed. WB-F344 cells exposed to thapsigargin (TG) were cocultured with PD-MSCs or PD-MSCsPRL−1.

Results
ER stress markers, e.g., eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were increased in the nontransplantation group (NTx) compared to the control group. PD-MSCsPRL−1 significantly decreased ER stress markers compared to NTx and induced dynamic changes in calcium channel markers, e.g., sarco/endoplasmic reticulum Ca2+ -ATPase 2b (SERCA2b), inositol 1,4,5-trisphosphate receptor (IP3R), mitochondrial calcium uniporter (MCU), and voltage-dependent anion channel 1 (VDAC1) (*p < 0.05). Cocultivation of TG-treated WB-F344 cells with PD-MSCsPRL−1 decreased cytosolic calmodulin (CaM) expression and cytosolic and mitochondrial Ca2+ concentrations. However, the ER Ca2+ concentration was increased compared to PD-MSCs (*p  < 0.05). PRL-1 activated phosphatidylinositol-3-kinase (PI3K) signaling via epidermal growth factor receptor (EGFR), which resulted in calcium increase via CaM expression.

Conclusions
These findings suggest that PD-MSCsPRL−1 improved hepatic functions via calcium changes and attenuated ER stress in a BDL-injured rat model. Therefore, these results provide useful data for the development of next-generation MSC-based stem cell therapy for regenerative medicine in chronic liver disease.
A high abundance of Firmicutes in the intestine of chinese mitten crabs (Eriocheir sinensis) cultured in an alkaline region
Authors: Guan Weibing , Li Kui , Zhao Shuang , Li Kejun 
Published: October 2021

AbstractThe Chinese mitten crab (Eriocheir sinensis) is a popular aquaculture product in East Asia, especially in China. In the last decade, rice–crab co-culture has rapidly expanded in China. Under this model, crabs are raised in rice fields instead of in traditional aquaculture ponds. In this study, we cultured two varieties of Chinese mitten crabs (Changjiang and Liaohe) in an alkaline region in northwest China and used Illumina MiSeq sequencing to compare the intestinal bacterial alpha diversity and community structure between traditional and co-culture aquaculture models, between two crab varieties, and between female and male crabs. Significant variations in intestinal bacterial communities were found between crab varieties and between female and male crabs but not between aquaculture models. These results show that rice–crab co-culture operations did not obviously impact the crab intestinal bacterial community compared with traditional pond aquaculture. Firmicutes was the most abundant bacterial phylum in the crab intestines (78%, relative abundance). Three dominant operational taxonomic units (OTUs) represented 73.2% of Firmicutes sequences and 56.8% of all sequences. A dominant OTU assigned as Firmicutes that was negatively correlated with crab body length, width, and weight was found in the source water for the experimental area. The results of this study suggest that the aquaculture of Chinese mitten crabs in alkaline regions requires more study to improve cultivation techniques.
A class of backward stochastic Bellman–Bihari’s inequality and its applications
Authors: Hao Wu , Wang Jinxia 
Published: October 2021

AbstractIn this paper, we propose and prove several different forms of backward stochastic Bellman–Bihari’s inequality. Then, as two applications, two different types of the comparison theorems for backward stochastic differential equation with stochastic non-Lipschitz condition are presented.
Global strong solution to the 2D inhomogeneous incompressible magnetohydrodynamic fluids with density-dependent viscosity and vacuum
Authors: Su Menglong 
Published: October 2021

AbstractIn this paper, we investigate an initial boundary value problem for two-dimensional inhomogeneous incompressible MHD system with density-dependent viscosity. First, we establish a blow-up criterion for strong solutions with vacuum. Precisely, the strong solution exists globally if $\|\nabla \mu (\rho )\|_{L^{\infty }(0, T; L^{p})}$

∥
∇
μ
(
ρ
)
∥

L
∞

(
0
,
T
;

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p

)

is bounded. Second, we prove the strong solution exists globally (in time) only if $\|\nabla \mu (\rho _{0})\|_{L^{p}}$

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∇
μ
(

ρ
0

)
∥

L
p

is suitably small, even the presence of vacuum is permitted.