bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host-microbiome protein-protein interactions capture disease-relevant pathways
Authors: Zhou Hao , Beltrán Juan Felipe , Brito Ilana Lauren 
Published: March 2022

Abstract
Background
Host-microbe interactions are crucial for normal physiological and immune system development and are implicated in a variety of diseases, including inflammatory bowel disease (IBD), colorectal cancer (CRC), obesity, and type 2 diabetes (T2D). Despite large-scale case-control studies aimed at identifying microbial taxa or genes involved in pathogeneses, the mechanisms linking them to disease have thus far remained elusive.

Results
To identify potential pathways through which human-associated bacteria impact host health, we leverage publicly-available interspecies protein-protein interaction (PPI) data to find clusters of microbiome-derived proteins with high sequence identity to known human-protein interactors. We observe differential targeting of putative human-interacting bacterial genes in nine independent metagenomic studies, finding evidence that the microbiome broadly targets human proteins involved in immune, oncogenic, apoptotic, and endocrine signaling pathways in relation to IBD, CRC, obesity, and T2D diagnoses.

Conclusions
This host-centric analysis provides a mechanistic hypothesis-generating platform and extensively adds human functional annotation to commensal bacterial proteins.
LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial
Authors: Opgenorth Dawn , Baig Nadia , Fiest Kirsten , Karvellas Constantine , Kutsogiannis Jim , Lau Vincent , Macintyre Erika , Senaratne Janek , Slemko Jocelyn , Sligl Wendy , Wang Xiaoming , Bagshaw Sean M. , Rewa Oleksa G. 
Published: March 2022

Abstract
Background
Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited.

Methods
The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions.

Discussion
LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients.

Trial registration
ClinicalTrials.gov NCT05058612. Registered on September 28, 2021
Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial
Authors: Gagnon David J. , Ryzhov Sergey V. , May Meghan A. , Riker Richard R. , Geller Bram , May Teresa L. , Bockian Sarah , deKay Joanne T. , Eldridge Ashley , Van der Kloot Thomas , Lerwick Patricia , Lord Christine , Lucas F. Lee , Mailloux Patrick , McCrum Barbara , Searight Meghan , Wirth Joel , Zuckerman Jonathan , Sawyer Douglas , Seder David B. 
Published: March 2022

Abstract
Background
Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality.

Methods
The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years.

Discussion
The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome.

Trial registration
ClinicalTrials.gov NCT04999592. Registered on August 10, 2021.
d-Lactic acid production from agricultural residues by membrane integrated continuous fermentation coupled with B vitamin supplementation
Authors: Ma Kedong , Cui Yubo , Zhao Ke , Yang Yuxuan , Wang Yidan , Hu Guoquan , He Mingxiong 
Published: March 2022

Abstract
Background
d-Lactic acid played an important role in the establishment of PLA as a substitute for petrochemical plastics. But, so far, the d-lactic acid production was limited in only pilot scale, which was definitely unable to meet the fast growing market demand. To achieve industrial scale d-lactic acid production, the cost-associated problems such as high-cost feedstock, expensive nutrient sources and fermentation technology need to be resolved to establish an economical fermentation process.

Results
In the present study, the combined effect of B vitamin supplementation and membrane integrated continuous fermentation on d-lactic acid production from agricultural lignocellulosic biomass by Lactobacillus delbrueckii was investigated. The results indicated the specific addition of vitamins B1, B2, B3 and B5 (VB1, VB2, VB3 and VB5) could reduce the yeast extract (YE) addition from 10 to 3 g/l without obvious influence on fermentation efficiency. By employing cell recycling system in 350 h continuous fermentation with B vitamin supplementation, YE addition was further reduced to 0.5 g/l, which resulted in nutrient source cost reduction of 86%. A maximum d-lactate productivity of 18.56 g/l/h and optical purity of 99.5% were achieved and higher than most recent reports.

Conclusion
These findings suggested the novel fermentation strategy proposed could effectively reduce the production cost and improve fermentation efficiency, thus exhibiting great potential in promoting industrial scale d-lactic acid production from lignocellulosic biomass.

Graphical Abstract
Screening for odorant receptor genes expressed in Aedes aegypti involved in host-seeking, blood-feeding and oviposition behaviors
Authors: Ni Meng , Zhao Teng , Lv Hui-xin , Li Man-jin , Xing Dan , Zhao Tong-yan , Li Chun-xiao 
Published: March 2022

AbstractBackgroundAedes aegyptiis one of the most important vectors of zoonotic diseases worldwide, and its survival and reproductive processes depend heavily on its olfactory system. In this study, the expression levels of all odorant receptor (OR) genes ofAe. aegyptiwere explored during different physiological periods to identify olfactory genes that may be associated with mosquito blood-feeding and the search for oviposition sites.MethodsFour experimental groups, consisting ofAe. aegyptimales, pre-blood-feeding females, post-blood-feeding females and post-oviposition females, were established. A total of 114 pairs of primers targeting all messenger RNA encoded by OR genes were designed based on the whole genome ofAe. aegypti. The expression of OR genes was evaluated by real-time fluorescence quantitative PCR for relative quantification and the comparison of differences between groups.ResultsA total of 53 differentially expressed OR genes were identified between males and females inAe. aegyptiantennae. Also, eight, eight and 13 differentially expressed OR genes were identified in pre- versus post-blood-feeding females, in pre- versus post-oviposition females and in post-blood-feeding versus post-oviposition females, respectively. In addition, 16 OR genes were significantly differentially expressed in multiple physiological periods of the mosquitoes.ConclusionsA large number of ORs with significant intergroup differences and high expression levels were screened in this study. Some of these genes are reported for the first time, providing possible targets for the development of mosquito control pathways based on the olfactory system.Graphical Abstract
Amniotic suspension allograft improves pain and function in a rat meniscal tear-induced osteoarthritis model
Authors: Kimmerling Kelly A. , Gomoll Andreas H. , Farr Jack , Mowry Katie C. 
Published: March 2022

Abstract
Background
Osteoarthritis is a degenerative disease of the knee that affects 250 million people worldwide. Due to the rising incidence of knee replacement and revision surgery, there is a need for a nonsurgical treatment to reduce pain and improve function in patients with knee osteoarthritis. Placental-derived allografts, such as an amniotic suspension allograft (ASA), provide growth factors and cytokines that could potentially modulate the inflammatory environment of osteoarthritis. The purpose of this study was to evaluate the efficacy of ASA in a rat medial meniscal tear (MMT) induced osteoarthritis model through histology, microCT, synovial fluid biomarkers, and behavioral testing.

Methods
Rats underwent MMT surgery at day − 7; at day 0, rats were injected with either ASA, vehicle control, or fibroblast growth factor-18 (FGF18). Behavioral testing, including gait analysis, pain threshold, incapacitance, and knee swelling were evaluated in-life, along with histology, microCT analysis of cartilage, and synovial fluid testing post-sacrifice. One MMT cohort was sacrificed at day 10, the other at day 21. A third cohort acted as a safety arm and did not receive MMT surgery; these rats were injected with either vehicle control or ASA and evaluated at day 3 and day 21.

Results
Behavioral testing showed a significant improvement in pain threshold, incapacitance, and gait following an injection of ASA. MicroCT showed significant improvements in cartilage thickness and attenuation at day 10 only, and histology showed no detrimental effects compared to the vehicle control at day 21. Synovial fluid analysis showed a significant increase in anti-inflammatory IL-10. The safety cohort showed no significant differences except for an increase in synovitis at day 21, which could be evidence of a xenogeneic response in this model.

Conclusions
In this study, an injection of ASA was well tolerated with no adverse events. Improvements in pain and function, along with cartilage properties at day 10, were observed. Increases in anti-inflammatory cytokines was also seen, along with no significant cartilage degeneration at day 21 compared to the vehicle control. This study provides evidence for the use of ASA as a nonsurgical treatment for knee OA.
DeSIDE-DDI: interpretable prediction of drug-drug interactions using drug-induced gene expressions
Authors: Kim Eunyoung , Nam Hojung 
Published: March 2022

AbstractAdverse drug-drug interaction (DDI) is a major concern to polypharmacy due to its unexpected adverse side effects and must be identified at an early stage of drug discovery and development. Many computational methods have been proposed for this purpose, but most require specific types of information, or they have less concern in interpretation on underlying genes. We propose a deep learning-based framework for DDI prediction with drug-induced gene expression signatures so that the model can provide the expression level of interpretability for DDIs. The model engineers dynamic drug features using a gating mechanism that mimics the co-administration effects by imposing attention to genes. Also, each side-effect is projected into a latent space through translating embedding. As a result, the model achieved an AUC of 0.889 and an AUPR of 0.915 in unseen interaction prediction, which is competitively very accurate and outperforms other state-of-the-art methods. Furthermore, it can predict potential DDIs with new compounds not used in training. In conclusion, using drug-induced gene expression signatures followed by gating and translating embedding can increase DDI prediction accuracy while providing model interpretability. The source code is available on GitHub (https://github.com/GIST-CSBL/DeSIDE-DDI).
Use of GC-IMS for detection of volatile organic compounds to identify mixed bacterial culture medium
Authors: Lu Yanyi , Zeng Lin , Li Min , Yan Bowen , Gao Dandan , Zhou Bangfu , Lu Weiping , He Qinghua 
Published: March 2022

AbstractIn order to explore the possibility to identify common wound infection bacteria in mixed culture with gas chromatograph-ion migration spectroscopy (GC-IMS), the headspace gas of single and mixed cultures of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were detected and analyzed by GC-IMS system. The bacteria were cultured in thioglycolate medium tubes then transferred to the sampling bottles (indirect method), or directly cultured in the sampling bottles (direct method) to allow accumulation of volatile compounds and facilitate automation. The specific microorganism volatile organic compounds (mVOCs) of the three bacteria were obtained. Some of them have been known to certain substance, for example, ethanol, isoamyl acetate, Phenylacetaldehyde, 2-heptanone etc., while others have not. Principal component analysis (PCA) showed that a higher separability can be achieved with direct method than indirect method. This work indicated that it is possible to identify compound bacteria by detecting specific mVOCs with GC-IMS, and the specific mVOCs should be medium-dependent.
Climate trend analysis for a semi-arid Borana zone in southern Ethiopia during 1981–2018
Authors: Worku Mitiku Adisu , Feyisa Gudina Legese , Beketie Kassahun Ture 
Published: March 2022

Abstract
Background
Understanding the climate variability at local scale could help suggest local adaptation responses to manage climate associated risks. This paper analyzed the variability and trend of climate in semi-arid Borana zone of southern Ethiopia over the period 1981–2018 using Mann–Kendall (MK) test, Sen’s Slope Estimator (SEE) and inverse distance weighted (IDW) interpolation technique. Gridded (4 km * 4 km) climate data (daily precipitation, daily maximum temperature (Tmax) and minimum temperature (Tmin)) were collected from National Meteorology Agency (NMA) of Ethiopia.

Results
The results revealed the study area received a mean monthly precipitation of 39.19 mm and a monthly mean Tmax and Tmin of 29.66 °C and 16.31 °C were observed respectively. Rainfall shows a significant increasing trend during August, October and November and extremely variable during December, January and February where CV > 100%. Tmax shows a significant warming trend during August but January, February, August and October exhibited similar trend for Tmin. Rainfall and Tmin shows a significant trend during Meher and no trend for the rest of the seasons. Mean annual rainfall shows a significant increase where no trend observed for both Tmax and Tmin at this timescale. Decadal rainfall and Tmin exhibited no trend but Tmax show significant warming trend during 2001–2010 decade. Better rainfall and cooler temperature were observed in the north central, northeastern and northwestern whereas the southeastern and southwestern regions were drier and warmer.

Conclusion
Rainfall is highly variable than temperature both at temporal and spatial scales in Borana. The intensity of rainfall decreases from the northeastern and northwestern parts towards the southwest while temperature increased from the north central parts towards the southwest for Tmax and the southeast for Tmin. The effect of topography is substantial for the local scale variability observed in the study area. Internal variability is observed at temporal and spatial scales and therefore any adaptation responses to local climate variability should consider the microscale climate.
Extensive metagenomic analysis of the porcine gut resistome to identify indicators reflecting antimicrobial resistance
Authors: Zhou Yunyan , Fu Hao , Yang Hui , Wu Jinyuan , Chen Zhe , Jiang Hui , Liu Min , Liu Qin , Huang Lusheng , Gao Jun , Chen Congying 
Published: March 2022

Abstract
Background
Antimicrobial resistance (AMR) has been regarded as a major threat to global health. Pigs are considered an important source of antimicrobial resistance genes (ARGs). However, there is still a lack of large-scale quantitative data on the distribution of ARGs in the pig production industry. The bacterial species integrated ARGs in the gut microbiome have not been clarified.

Results
In the present study, we used deep metagenomic sequencing data of 451 samples from 425 pigs including wild boars, Tibetan pigs, and commercial or cross-bred experimental pigs under different rearing modes, to comprehensively survey the diversity and distribution of ARGs and detect the bacteria integrated in these ARGs. We identified a total of 1295 open reading frames (ORFs) recognized as antimicrobial resistance protein-coding genes. The ORFs were clustered into 349 unique types of ARGs, and these could be further classified into 69 drug resistance classes. Tetracycline resistance was most enriched in pig feces. Pigs raised on commercial farms had a significantly higher AMR level than pigs under semi-free ranging conditions or wild boars. We tracked the changes in the composition of ARGs at different growth stages and gut locations. There were 30 drug resistance classes showing significantly different abundances in pigs between 25 and 240 days of age. The richness of ARGs and 41 drug resistance classes were significantly different between cecum lumen and feces in pigs from commercial farms, but not in wild boars. We identified 24 bacterial species that existed in almost all tested samples (core bacteria) and were integrated 128 ARGs in their genomes. However, only nine ARGs of these 128 ARGs were core ARGs, suggesting that most of the ARGs in these bacterial species might be acquired rather than constitutive. We selected three subsets of ARGs as indicators for evaluating the pollution level of ARGs in samples with high accuracy (r = 0.73~0.89).

Conclusions
This study provides a primary overview of ARG profiles in various farms under different rearing modes, and the data serve as a reference for optimizing the use of antimicrobials and evaluating the risk of pollution by ARGs in pig farms.
Enhancer promoter interactome and Mendelian randomization identify network of druggable vascular genes in coronary artery disease
Authors: Chignon Arnaud , Mathieu Samuel , Rufiange Anne , Argaud Déborah , Voisine Pierre , Bossé Yohan , Arsenault Benoit J. , Thériault Sébastien , Mathieu Patrick 
Published: March 2022

AbstractCoronary artery disease (CAD) is a multifactorial disorder, which is partly heritable. Herein, we implemented a mapping of CAD-associated candidate genes by using genome-wide enhancer-promoter conformation (H3K27ac-HiChIP) and expression quantitative trait loci (eQTL). Enhancer-promoter anchor loops from human coronary artery smooth muscle cells (HCASMC) explained 22% of the heritability for CAD. 3D enhancer-promoter genome mapping of CAD-genes in HCASMC was enriched in vascular eQTL genes. By using colocalization and Mendelian randomization analyses, we identified 58 causal candidate vascular genes including some druggable targets (MAP3K11, CAMK1D, PDGFD, IPO9 and CETP). A network analysis of causal candidate genes was enriched in TGF beta and MAPK pathways. The pharmacologic inhibition of causal candidate gene MAP3K11 in vascular SMC reduced the expression of athero-relevant genes and lowered cell migration, a cardinal process in CAD. Genes connected to enhancers are enriched in vascular eQTL and druggable genes causally associated with CAD.
Assessing preoperative hope and expectations related to functional neurosurgery: a new questionnaire
Authors: Radomska Michalina , Flores Alves dos Santos João , Weber Kerstin , Baertschi Marc , Burkhard Pierre R. , Herrmann François , Belayachi Sanaâ , Favez Nicolas , Canuto Alessandra 
Published: March 2022

AbstractBackgroundDespite successful functional neurosurgery, patients suffering from epilepsy or Parkinson’s disease may experience postoperative psychological distress and social maladjustments. Difficulties in coping with postoperative changes, even positive ones, have shown to be related to patients’ presurgery cognitive representations (i.e., expectations, hope). The aim of this study was to develop an instrument assessing various key features of surgery outcomes’ representations, namely the Preoperative Hope and Expectations Questionnaire (PHEQ).MethodsParticipants were patients (n= 50) diagnosed with Parkinson’s disease (n= 25) or epilepsy (n= 25), candidates for functional neurosurgery (i.e., Deep brain stimulation, anterior temporal lobectomy). Two to three weeks before the planned surgery, they were administrated items assessing their actual state, preoperative expectations, and hope regarding surgery outcomes. They also completed measures assessing optimism, quality of life and mood.ResultsExploratory analysis resulted in a 14-item version of the PHEQ composed of two factors (abstract representations, including psychological well-being andconcrete representations, such as direct surgery outcomes). The PHEQ demonstrated high internal consistency and good convergent validity. Patients were more prone to express postoperative improvements in terms of hope rather than expectations. They generally focused on concrete rather than abstract features, although patients with Parkinson’s disease had higher abstract future-oriented representations.ConclusionsThe PHEQ presents satisfactory psychometric properties and may be considered as a reliable instrument for research and clinical practice.