bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a nurse-led transitional burns rehabilitation programme (4Cs-TBuRP) for adult burn survivors: protocol for a randomised controlled trial
Authors: Bayuo Jonathan , Wong Frances Kam Yuet , Chung Loretta Yuet Foon 
Published: October 2021

Abstract
Background
Transitioning from the burn unit to the home/community can be chaotic with limited professional support. Some adult burn survivors may face varied concerns leading to poor outcomes in the early post-discharge period with limited access to professional help. Based on these, a nurse-led transitional burns rehabilitation programme has been developed and the current trial aims to ascertain its effects as well as explore the implementation process.

Methods
A single-centre, double-arm randomised controlled trial with a process evaluation phase will be utilised for this study. All adult burn survivors aged ≥ 18 years with burn size ≥ 10% total burn surface area at the site during the study period will be screened for eligibility at least 72 h to discharge. A sample size of 150 will be block randomised to treatment (receiving the nurse-led transitional care programme and routine post-discharge service) and control groups (receiving routine post-discharge service). The nurse-led transitional care programme comprises of predischarge and follow-up phases with the delivery of bundle of holistic interventions lasting for 8 weeks. There are three timelines for data collection: baseline, immediate post intervention, and 4 weeks post-intervention.

Discussion
The findings from this study can potentially inform the development and organisation of post-discharge care and affirm the need for ongoing comprehensive home-based care for burn survivors and their families

Trial registration
ClinicalTrials.govNCT04517721. Registered on 20 August 2020
Tryptophan plays an important role in yeast’s tolerance to isobutanol
Authors: Liu Hsien-Lin , Wang Christine H.-T. , Chiang En-Pei Isabel , Huang Chieh-Chen , Li Wen-Hsiung 
Published: October 2021

Abstract
Background
Isobutanol is considered a potential biofuel, thanks to its high-energy content and octane value, limited water solubility, and compatibility with gasoline. As its biosynthesis pathway is known, a microorganism, such as Saccharomyces cerevisiae, that inherently produces isobutanol, can serve as a good engineering host. Isobutanol’s toxicity, however, is a major obstacle for bioproduction. This study is to understand how yeast tolerates isobutanol.

Results
A S. cerevisiae gene-deletion library with 5006 mutants was used to screen genes related to isobutanol tolerance. Image recognition was efficiently used for high-throughput screening via colony size on solid media. In enrichment analysis of the 161 isobutanol-sensitive clones identified, more genes than expected were mapped to tryptophan biosynthesis, ubiquitination, and the pentose phosphate pathway (PPP). Interestingly, adding exogenous tryptophan enabled both tryptophan biosynthesis and PPP mutant strains to overcome the stress. In transcriptomic analysis, cluster analysis of differentially expressed genes revealed the relationship between tryptophan and isobutanol stress through some specific cellular functions, such as biosynthesis and transportation of amino acids, PPP, tryptophan metabolism, nicotinate/nicotinamide metabolism (e.g., nicotinamide adenine dinucleotide biosynthesis), and fatty acid metabolism.

Conclusions
The importance of tryptophan in yeast’s tolerance to isobutanol was confirmed by the recovery of isobutanol tolerance in defective strains by adding exogenous tryptophan to the growth medium. Transcriptomic analysis showed that amino acid biosynthesis- and transportation-related genes in a tryptophan biosynthesis-defective host were up-regulated under conditions similar to nitrogen starvation. This may explain why ubiquitination was required for the protein turnover. PPP metabolites may serve as precursors and cofactors in tryptophan biosynthesis to enhance isobutanol tolerance. Furthermore, the tolerance mechanism may also be linked to tryptophan downstream metabolism, including the kynurenine pathway and nicotinamide adenine dinucleotide biosynthesis. Both pathways are responsible for cellular redox balance and anti-oxidative ability. Our study highlights the central role of tryptophan in yeast’s isobutanol tolerance and offers new clues for engineering a yeast host with strong isobutanol tolerance.
Aedes aegypti: egg morphology and embryonic development
Authors: Mundim-Pombo Ana Paula Miranda , Carvalho Hianka Jasmyne Costa de , Rodrigues Ribeiro Rafaela , León Marisol , Maria Durvanei Augusto , Miglino Maria Angélica 
Published: October 2021

AbstractBackgroundThe diseases for whichAedes aegyptiis a vector are worrisome. The high vector competence of this mosquito, as well as its anthropophilia and ability to adapt to the urban environment, allows it to exploit many habitats, making its prevention an arduous task. Despite current disease control measures focused on the mosquito, the effectiveness in containing its dispersion still requires improvement; thus greater knowledge about this insect is fundamental.MethodsAedes aegypti egg morphology and embryonic development were analyzed from eggs of the insectary of the Institute of Biomedical Sciences of the University of São Paulo. Optical (light and confocal) and electronic (transmission and scanning) microscopy were used to analyze the morphological and ultrastructural features of the eggs. Embryos were observed in the initial (0–20.5 h after egg-laying), intermediate (20.6–40.1 h after egg-laying), and final (40.2–61.6 h) stages of development, and kept at a temperature of 28 °C ± 1 °C until collection for processing.ResultsEggs ofAe. aegyptiwere whitish at the time of oviposition, and then quickly became black. The egg length was 581.45 ± 39.73 μm and the width was 175.36 ± 11.59. Access to the embryo was difficult due to the egg morphology, point of embryonic development, and difficult permeability of the exochorion (mainly in fixation). Only about 5% of the collected eggs were successfully processed. In the initial stage of embryonic development, characteristics suggestive of intense cellular activity were found. In the intermediate stage, the beginning of the segmentation process was evident. In the final phase, it was possible to differentiate the cephalic region and the thoracic and abdominal segments.ConclusionThe chorion was found to be an important protective barrier and a limiting factor for the evaluation of the embryos and mosquito embryonic cells, indicating that further studies need to be carried out to identify the reason that this occurs.Graphical abstract
Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma
Authors: Usyk Mykhaylo , Pandey Abhishek , Hayes Richard B. , Moran Una , Pavlick Anna , Osman Iman , Weber Jeffrey S. , Ahn Jiyoung 
Published: October 2021

AbstractBackgroundImmune checkpoint blockade (ICB) shows lasting benefits in advanced melanoma; however, not all patients respond to this treatment and many develop potentially life-threatening immune-related adverse events (irAEs). Identifying individuals who will develop irAEs is critical in order to improve the quality of care. Here, we prospectively demonstrate that the gut microbiome predicts irAEs in melanoma patients undergoing ICB.MethodsPre-, during, and post-treatment stool samples were collected from 27 patients with advanced stage melanoma treated with IPI (anti-CTLA-4) and NIVO (anti-PD1) ICB inhibitors at NYU Langone Health. We completed 16S rRNA gene amplicon sequencing, DNA deep shotgun metagenomic, and RNA-seq metatranscriptomic sequencing. The divisive amplicon denoising algorithm (DADA2) was used to process 16S data. Taxonomy for shotgun sequencing data was assigned using MetaPhlAn2, and gene pathways were assigned using HUMAnN 2.0. Compositionally aware differential expression analysis was performed using ANCOM. The Cox-proportional hazard model was used to assess the prospective role of the gut microbiome (GMB) in irAES, with adjustment for age, sex, BMI, immune ICB treatment type, and sequencing batch.ResultsTwo natural GMB clusters with distinct community compositions were identified from the analysis of 16S rRNA data (R2= 0.16,p< 0.001). In Cox-proportional hazard modeling, these two clusters showed a near 7-fold differential risk for developing irAEs within 1 year of initiating treatment (HR = 6.89 [95% CI: 1.33–35.58]). Using shotgun metagenomics, we further identified 37 bacterial strains differentially expressed between the risk groups, with specific dominance ofBacteroides doreiwithin the high-risk GMB cluster andBacteroides vulgatusin the low-risk cluster. The high-risk cluster also appeared to have elevated expression of several functional pathways, including those associated with adenosine metabolism (all FDR < 0.05). A sub-analysis of samples (n= 10 participants) at baseline and 6 and 12 weeks after the start of treatment revealed that the microbiome remained stable over the course of treatment (R2= 0.88,p< 0.001).ConclusionsWe identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients.
Intra-patient stability of tumor mutational burden from tissue biopsies at different time points in advanced cancers
Authors: Pham Timothy V. , Goodman Aaron M. , Sivakumar Smruthy , Frampton Garrett , Kurzrock Razelle 
Published: October 2021

Abstract
Background
Tumor mutational burden (TMB) may be a predictive biomarker of immune checkpoint inhibitor (ICI) responsiveness. Genomic landscape heterogeneity is a well-established cancer feature. Molecular characteristics may differ even within the same tumor specimen and undoubtedly evolve with time. However, the degree to which TMB differs between tumor biopsies within the same patient has not been established.

Methods
We curated data on 202 patients enrolled in the PREDICT study (NCT02478931), seen at the University of California San Diego (UCSD), who had 404 tissue biopsies for TMB (two per patient, mean of 722 days between biopsies) to assess difference in TMB before and after treatment in a pan-cancer cohort. We also performed an orthogonal analysis of 2872 paired pan-solid tumor biopsies in the Foundation Medicine database to examine difference in TMB between first and last biopsies.

Results
The mean (95% CI) TMB difference between samples was 0.583 [− 0.900–2.064] (p = 0.15). Pearson correlation showed a flat line for time elapsed between biopsies versus TMB change indicating no correlation (R2 = 0.0001; p = 0.8778). However, in 55 patients who received ICIs, there was an increase in TMB (before versus after mean mutations/megabase [range] 12.50 [range, 0.00–98.31] versus 14.14 [range, 0.00–100.0], p = 0.025). Analysis of 2872 paired pan-solid tumor biopsies in the Foundation Medicine database also indicated largely stable TMB patterns; TMB increases were only observed in specific tumors (e.g., breast, colorectal, glioma) within certain time intervals.

Conclusions
Overall, our results suggest that tissue TMB remains stable with time, though specific therapies such as immunotherapy may correlate with an increase in TMB.

Trial registration
NCT02478931, registered June 23, 2015.
There is a world beyond αvβ3-integrin: Multimeric ligands for imaging of the integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1 by positron emission tomography
Authors: Steiger Katja , Quigley Neil Gerard , Groll Tanja , Richter Frauke , Zierke Maximilian Alexander , Beer Ambros Johannes , Weichert Wilko , Schwaiger Markus , Kossatz Susanne , Notni Johannes 
Published: October 2021

AbstractBackgroundIn the context of nuclear medicine and theranostics, integrin-related research and development was, for most of the time, focused predominantly on 'RGD peptides' and the subtype αvβ3-integrin. However, there are no less than 24 known integrins, and peptides without the RGD sequence as well as non-peptidic ligands play an equally important role as selective integrin ligands. On the other hand, multimerization is a well-established method to increase the avidity of binding structures, but multimeric radiopharmaceuticals have not made their way into clinics yet. In this review, we describe how these aspects have been interwoven in the framework of the German Research Foundation's multi-group interdisciplinary funding scheme CRC 824, yielding a series of potent PET imaging agents for selective imaging of various integrin subtypes.ResultsThe gallium-68 chelator TRAP was utilized to elaborate symmetrical trimers of various peptidic and non-peptidic integrin ligands. Preclinical data suggested a high potential of the resulting Ga-68-tracers for PET-imaging of the integrins α5β1, αvβ8, αvβ6, and αvβ3. For the first three, we provide some additional immunohistochemistry data in human cancers, which suggest several future clinical applications. Finally, application of αvβ3- and αvβ6-integrin tracers in pancreatic carcinoma patients revealed that unlike αvβ3-targeted PET, αvβ6-integrin PET is not characterized by off-target uptake and thus, enables a substantially improved imaging of this type of cancer.ConclusionsNovel radiopharmaceuticals targeting a number of different integrins, above all, αvβ6, have proven their clinical potential and will play an increasingly important role in future theranostics.
Current knowledge and challenges associated with targeted delivery of neurotrophic factors into the central nervous system: focus on available approaches
Authors: Bahlakeh Gozal , Rahbarghazi Reza , Mohammadnejad Daruosh , Abedelahi Ali , Karimipour Mohammad 
Published: October 2021

AbstractDuring the last decades, numerous basic and clinical studies have been conducted to assess the delivery efficiency of therapeutic agents into the brain and spinal cord parenchyma using several administration routes. Among conventional and in-progress administrative routes, the eligibility of stem cells, viral vectors, and biomaterial systems have been shown in the delivery of NTFs. Despite these manifold advances, the close association between the delivery system and regeneration outcome remains unclear. Herein, we aimed to discuss recent progress in the delivery of these factors and the pros and cons related to each modality.
Predictors of adherence to an internet-based cognitive behavioral therapy program for individuals with chronic pain and comorbid psychological distress
Authors: Gasslander Nils , Alfonsson Sven , Jackalin Amanda , Tengberg Cecilia , Håkansson Johanna , Huotari Linda , Buhrman Monica 
Published: October 2021

AbstractBackgroundThe burden caused by chronic pain is significant, affecting at least 10 percent of the world´s population. While internet-based treatments based on cognitive behavioral therapy (CBT) have been shown to be promising in this area, attrition levels vary significantly. The purpose of this study was to investigate predictor variables for participants’ adherence to an internet-based CBT treatment for individuals with chronic pain as well as to investigate associations between adherence and treatment outcome.MethodsData for this study was retrieved from a randomized controlled trial including 95 individuals with chronic pain who received internet-based CBT. Treatment adherence was studied through three outcome variables: treatment progress, treatment completion and exercise completion. The predictor variables were grouped into four clusters: background variables (age, gender, marital status, level of education, and typical computer usage); the second cluster included health status variables (sick leave, current psychiatric diagnosis, previous psychotherapy for pain, current pharmacological treatment, previous depression, current depression, and current depressive symptoms); the third cluster included pain-related variables (opioid medication, history of pain, and pain symptoms) and the fourth cluster included motivation variables (measured with treatment preference, treatment credibility, compliance to the treatment schedule and contact with the therapists).ResultsFindings showed that treatment progress was predicted by higher treatment credibility at baseline, whereas participants who were behind schedule in the second week of the program finished fewer treatment modules. When analyzing each cluster of predictor variables separately, current depressive symptoms also predicted fewer completed treatment modules.Among the pain-related variables, higher pain acceptance was the only predictor for completing more treatment modules. Treatment completion (which in this study was defined as having completed at least 75% of treatment modules) was predicted by higher treatment credibility and fewer depressive symptoms at baseline, and was thus similar to the results regarding treatment progress. Finally, all adherence variables predicted the treatment outcome pain interference.ConclusionsLow treatment credibility, depressive symptoms and falling behind the treatment schedule early on were the most important predictor variables for low treatment adherence, while a number of demographical and pain-related variables were not related to adherence. The results from this study may help clinicians identify patients who are less likely to complete, and thus benefit from, their pain treatment.Trial registrationClinicalTrials.gov NTC03316846.
Writing group program reduces academic procrastination: a quasi-experimental study
Authors: Patria Bhina , Laili Latifatul 
Published: October 2021

Abstract
Background
Procrastination is a common problem in higher education. It leads to negative consequences on students’ health and academic achievement. Nevertheless, research concerning interventions has not yet produced consistent results. This study aims to examine the effectiveness of a writing group program on reducing academic procrastination.

Methods
This study was a quasi-experimental study with a one-group pretest-posttest design using double pretests. A double pretest design was used to ensure the internal validity of the experiment. Twenty graduate students followed a 15-days writing group program consisted of a training session and four sessions of writing groups. A thesis procrastination scale was used to measure the intervention’s effects.

Results
The writing group program helped students to set a writing target, discussed writing progress, and provided social support to their colleagues. The results showed that the intervention program could significantly decrease academic procrastination.

Conclusion
The present study demonstrated that a writing group could potentially reduce academic procrastination. Thus, students could benefit from a writing group when working on their master thesis. A thesis preparation course that provides information about goal-setting strategy and the principles of effective writing habits (i.e., behavioral, artisanal, social and emotional habits), might also assist students in writing their thesis. Further research is needed, preferably through the provision of a control group, a randomized assignment and a larger sample.
Highly accurate and efficient two phase-intrusion detection system (TP-IDS) using distributed processing of HADOOP and machine learning techniques
Authors: Jadhav Abhijit Dnyaneshwar , Pellakuri Vidyullatha 
Published: October 2021

AbstractNetwork security and data security are the biggest concerns now a days. Every organization decides their future business process based on the past and day to day transactional data. This data may consist of consumer’s confidential data, which needs to be kept secure. Also, the network connections when established with the external communication devices or entities, a care should be taken to authenticate these and block the unwanted access. This consists of identification of the malicious connection nodes and identification of normal connection nodes. For that, we use a continuous monitoring of the network input traffic to recognize the malicious connection request called as intrusion and this type of monitoring system is called as an Intrusion detection system (IDS). IDS helps us to protect our network and data from insecure and malicious network connections. Many such systems exists in the real time scenario, but they have critical issues of performance like accuracy and efficiency. These issues are addressed as a part of this research work of IDS using machine learning techniques and HDFS. The TP-IDS is designed in two phases for increasing accuracy. In phase I of TP-IDS, Support Vector Machine (SVM) and k Nearest Neighbor (kNN) are used. In phase II of TP-IDS, Decision Tree (DT) and Naïve Bayes (NB) are used, where phase II is the validation phase of the system for increasing accuracy. Also, both the phases are having Hadoop distributed file system underlying data storage and processing architecture, which allows parallel processing to increase the speed of the system and hence achieve the efficiency in TP-IDS.
Biological and synthetic approaches to inhibiting nitrification in non-tilled Mediterranean soils
Authors: Bozal-Leorri Adrián , Corrochano-Monsalve Mario , Arregui Luis Miguel , Aparicio-Tejo Pedro M. , González-Murua Carmen 
Published: October 2021

AbstractBackgroundThe increasing demand for food production has led to a tenfold increase in nitrogen (N) fertilizer use since the Green Revolution. Nowadays, agricultural soils have been turned into high-nitrifying environments that increase N pollution. To decrease N losses, synthetic nitrification inhibitors (SNIs) such as 3,4-dimethylpyrazole phosphate (DMPP) have been developed. However, SNIs are not widely adopted by farmers due to their biologically limited stability and soil mobility. On the other hand, allelopathic substances from root exudates from crops such as sorghum are known for their activity as biological nitrification inhibitors (BNIs). These substances are released directly into the rhizosphere. Nevertheless, BNI exudation could be modified or even suppressed if crop development is affected. In this work, we compare the performance of biological (sorghum crop) and synthetic (DMPP) nitrification inhibitors in field conditions.ResultsSorghum crop BNIs and DMPP prevented an increase in the abundance of ammonia-oxidizing bacteria (AOB) without affecting the total bacterial abundance. Both nitrification inhibitors maintained similar soil NH4+content, but at 30 days post-fertilization (DPF), the sorghum BNIs resulted in higher soil NO3−content than DMPP. Even so, these inhibitors managed to reduce 64% and 96%, respectively, of the NO3−-N/NH4+-N ratio compared to the control treatment. Similar to soil mineral N, there were no differences in leaf δ15N values between the two nitrification inhibitors, yet at 30 DPF, δ15N values from sorghum BNI were more positive than those of DMPP. N2O emissions from DMPP-treated soil were low throughout the experiment. Nevertheless, while sorghum BNIs also maintained low N2O emissions, they were associated with a substantial N2O emission peak at 3 DPF that lasted until 7 DPF.ConclusionsOur results indicate that while sorghum root exudates can reduce nitrification in field soil, even at the same efficiency as DMPP for a certain amount of time, they are not able to prevent the N pollution derived from N fertilization as DMPP does during the entire experiment.Graphic Abstract