bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced thermal and alkaline stability of L-lysine decarboxylase CadA by combining directed evolution and computation-guided virtual screening
Authors: Xi Yang , Ye Lidan , Yu Hongwei 
Published: March 2022

AbstractAs an important monomer for bio-based nylons PA5X, cadaverine is mainly produced by enzymatic decarboxylation of L-lysine. A key issue with this process is the instability of L-lysine decarboxylase (CadA) during the reaction due to the dissociation of CadA subunits with the accumulation of alkaline cadaverine. In this work, we attempted to improve the thermal and alkaline stability of CadA by combining directed evolution and computation-guided virtual screening. Interestingly, site 477 residue located at the protein surface and not the decamer interface was found as a hotspot in directed evolution. By combinatorial mutagenesis of the positive mutations obtained by directed evolution and virtual screening with the previously reported T88S mutation, K477R/E445Q/T88S/F102V was generated as the best mutant, delivering 37% improvement of cadaverine yield at 50 ºC and pH 8.0. Molecular dynamics simulations suggested the improved rigidity of regional structures, increased number of salt bridges, and enhancement of hydrogen bonds at the multimeric interface as possible origins of the improved stability of the mutant. Using this four-point mutant, 160.7 g/L of cadaverine was produced from 2.0 M Lysine hydrochloride at 50 °C without pH regulation, with a conversion of 78.5%, whereas the wild type produced 143.7 g/L cadaverine, corresponding to 70% conversion. This work shows the combination of directed evolution and virtual screening as an efficient protein engineering strategy.
Graphical Abstract
Tailoring pullulanase PulAR from Anoxybacillus sp. AR-29 for enhanced catalytic performance by a structure-guided consensus approach
Authors: Li Shu-Fang , Xu Shen-Yuan , Wang Ya-Jun , Zheng Yu-Guo 
Published: March 2022

AbstractPullulanase is a well-known debranching enzyme that can specifically hydrolyze α-1,6-glycosidic linkages in starch and oligosaccharides, however, it suffers from low stability and catalytic efficiency under industrial conditions. In the present study, four residues (A365, V401, H499, and T504) lining the catalytic pocket of Anoxybacillus sp. AR-29 pullulanase (PulAR) were selected for site-directed mutagenesis (SDM) by using a structure-guided consensus approach. Five beneficial mutants (PulAR-A365V, PulAR-V401C, PulAR-A365/V401C, PulAR-A365V/V401C/T504V, and PulAR-A365V/V401C/T504V/H499A) were created, which showed enhanced thermostability, pH stability, and catalytic efficiency. Among them, the quadruple mutant PulAR-A365V/V401C/T504V/H499A displayed 6.6- and 9.6-fold higher catalytic efficiency toward pullulan at 60 ℃, pH 6.0 and 5.0, respectively. In addition, its thermostabilities at 60 ℃ and 65 ℃ were improved by 2.6- and 3.1-fold, respectively, compared to those of the wild-type (WT). Meanwhile, its pH stabilities at pH 4.5 and 5.0 were 1.6- and 1.8-fold higher than those of WT, respectively. In summary, the catalytic performance of PulAR was significantly enhanced by a structure-guided consensus approach. The resultant quadruple mutant PulAR-A365V/V401C/T504V/H499A demonstrated potential applications in the starch industry.
Graphical Abstract
Supramolecular protein assembly in cell-free protein synthesis system
Authors: Li Zhixia , Li Yuting , Lin Xiaomei , Cui Yuntao , Wang Ting , Dong Jian , Lu Yuan 
Published: March 2022

AbstractProtein-based biomaterials have the characteristics of stability and biocompatibility. Based on these advantages, various bionic materials have been manufactured and used in different fields. However, current protein-based biomaterials generally need to form monomers in cells and be purified before being assembled in vitro. The preparation process takes a long time, and the complex cellular environment is challenging to be optimized for producing the target protein product. Here this study proposed technology for in situ synthesis and assembly of the target protein, namely the cell-free protein synthesis (CFPS), which allowed to shorten the synthesis time and increase the flexibility of adding or removing natural or synthetic components. In this study, successful expression and self-assembly of the dihedral symmetric proteins proved the applicability of the CFPS system for biomaterials production. Furthermore, the fusion of different functional proteins to these six scaffold proteins could form active polymers in the CFPS system. Given the flexibility, CFPS is expected to become a powerful tool as the prototyping and manufacturing technology for protein-based biomaterials in the future.
Graphical Abstract
Precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model
Authors: Henry E. Courtney , Strugari Matthew , Mawko George , Brewer Kimberly , Liu David , Gordon Andrew C. , Bryan Jeffrey N. , Maitz Charles , Karnia James J. , Abraham Robert , Kappadath S. Cheenu , Syme Alasdair 
Published: March 2022

AbstractPurposeTo perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry.Materials and methodsA CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland–Altman analysis.ResultsA linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r2 > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r2 = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10−12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland–Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively.ConclusionThe benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose–response relationship, which could ultimately improve future patient outcomes.
Clostridium perfringens sepsis after pancreatoduodenectomy: a case report
Authors: Takahashi Goro , Nakamura Yoshiharu , Hayakawa Tomohiro , Ono Takashi , Endo Kazuhiko , Yoshida Hiroshi 
Published: March 2022

Abstract
Background
Clostridium perfringens sepsis associated with massive intravascular hemolysis has an extremely poor prognosis. We here report a case of C. perfringens sepsis associated with massive intravascular hemolysis that developed secondary to a post-pancreaticoduodenectomy (PD) hepatic abscess.

Case presentation
A 70-year-old man with Type 2 diabetes underwent PD for an ampulla of Vater carcinoma. His postoperative course was uneventful. He was discharged on the 16th post-operative day (POD 16) after confirming no major abnormalities on abdominal contrast computed tomography (CT) on POD 14 or laboratory results on POD 16. Two days after discharge, he was readmitted because of fever and chills. Laboratory tests showed only a mild inflammatory reaction (white blood cell count, 11,980/mm3; C-reactive protein, 2.07 mg/dL). Abdominal CT showed an irregular, approximately 20-mm diameter, low-density area in the liver S6 region that had not been seen on a recent previous scan. We initially suspected postoperative cholangitis associated with biliary reconstruction and started empirical treatment with sulbactam/ampicillin after drawing blood for culture. Eight hours after admission, he developed septic shock with body temperature 40.0 ℃ and blood pressure 70/40 mm Hg. Laboratory findings showed a severe inflammatory reaction, severe anemia, and massive hemolysis (white blood cell count, 37,400/mm3; hemoglobin, 7.7 g/dL; total bilirubin, 8.05 mg/dL; direct bilirubin, 2.66 mg/dL; and lactate dehydrogenase, 1686 U/L). Hemoglobinuria was noted in the urinary catheter output. Repeat CT 9 h after admission showed the low-density area in S6 had become a gas-forming abscess. C. perfringens sepsis was strongly suspected on the basis of these findings and the abscess was drained percutaneously immediately after its diagnosis. His vital signs improved dramatically and he recovered within 24 h. Blood and abscess cultures grew C. perfringens 4 days after admission, leading to a definitive diagnosis of C. perfringens sepsis associated with massive intravascular hemolysis. He was discharged 18 days after admission. His sepsis has not recurred.

Conclusions
Clostridium perfringens infection should be considered in patients who have undergone PD and present with gas-forming hepatic abscesses and/or sepsis associated with intravascular hemolysis. Prompt aggressive treatment is crucial, because C. perfringens infections can cause death within hours.
Prevalence of soil-transmitted helminths infections among preschool and school-age children in Ethiopia: a systematic review and meta-analysis
Authors: Chelkeba Legese , Mekonnen Zeleke , Emana Daniel , Jimma Worku , Melaku Tsegaye 
Published: March 2022

AbstractBackgroundThere is a lack of comprehensive national data on prevalence, geographical distribution of different species, and temporal trends in soil-helminthiasis (STHs). Therefore, this study aimed to provide a summary and location of the available data on STHs infection among preschool and school-age children in Ethiopia.MethodsThe search was carried out in Medline via PubMed, Scopus, Science Direct, Web of Science, and Google Scholar on data published between 1997 to February 2020 for studies describing the rate of STHs infection among preschool and school-age in Ethiopian. We followed the Patient, Intervention, Comparison, and Outcome (PICO) approach to identify the studies. Meta-regression was performed to understand the trends and to summarize the prevalence using the “metaprop” command using STATA software version 14.0ResultsA total of 29,311 of the 61,690 children examined during the period under review were infected with one or more species of intestinal parasites yielding an overall prevalence of 48% (95% CI: 43–53%). The overall pooled estimate of STHs was 33% (95% CI: 28–38%). The prevalence was 44% (95% CI: 31–58%) in SNNPR, 34% (95% CI: 28–41%) in Amhara region, 31% (95% CI: 19–43%) in Oromia region and 10% (95% CI: 7–12%) in Tigray region. Soil-transmitted helminths infection rate has been decreasing from 44% (95% CI: 30–57%) pre-Mass Drug Administration (MDA) era (1997–2012) to 30% (95% CI: 25–34%) post-MDA (2013–2020), although statistically not significant (p = 0.45).A lumbricoideswas the predominant species with a prevalence of 17%.ConclusionSouthern Nations Nationalities and Peoples Region, Amhara, and Oromia regions carry the highest-burden and are categorized to Moderate Risk Zones (MRZ) and therefore, requiring MDA once annually with Albendazole or Mebendazole. The prevalence of STHs decreased after MDA compared to before MDA, but the decline was not statistically significant.A. lumbricoideswas the predominant species of STHs among preschool and school-age children in Ethiopia. The high prevalence of STHs observed in this review, underscores the need for better control and prevention strategies in Ethiopia.
Workflow in a pediatric neuro-oncology center
Authors: Rady Mohamed Reda 
Published: March 2022

Abstract
Introduction
Medical workflow is defined as task, process and medical staff working together in a specialized multidisciplinary team to deliver proper healthcare and achieve patient satisfaction with good patient experience such as in neuro-oncology centers which deal with central nervous system tumors. The aim of this article is to review workflow of a neuro-oncology center focusing on how to maintain patient satisfaction with the best health care outcome.

Main body
An organized workflow system in a neuro-oncology center is based on a multidisciplinary team of specialized and experienced neurosurgeons, pediatric oncologist, neuroradiologist, neuropathologist and radiotherapy oncologist where the patient is assigned to a primary oncologist and the decision regarding the surgical intervention is decided first by the pediatric neurosurgeon. The optimum workflow in a high flow neuro-oncology center starts with screening of all the referred cases to select those who match the mission and resources of the center to avoid overloading that affects the time and quality for care giving. Admission protocols must differentiate between elective and emergent admissions, centralization of caseload and proper scheduling of operations and outpatient visits. Clinical documentation is mandatory, and the efficiency and effectiveness of electronic health records (EHR) allows for tracing the work and tasks, proper coordination between multidisciplinary teams and generation of national cancer registries. Surgical intervention is followed by chemotherapy and/or radiotherapy according to pre-planned protocols for every specific pathology that is diagnosed by the neuropathologist. As the management of many neuro-oncology cases is complex and may require individualization, multidisciplinary team meetings involving extensive discussions are analysis for the best management plan.

Conclusion
A high flow neuro-oncology center requires a well-planned, and organized multidisciplinary team maintaining workflow system to improve the health outcome, and patient’s compliance and experience.
The Self-Appraisal of Masking Instrument
Authors: Block Ray , Plutzer Eric 
Published: March 2022

AbstractWe explore mask-wearing behavior during the coronavirus pandemic using the Self-Appraisal of Masking Instrument (SAMI). We situate this survey-based instrument within a theory in which the decision to mask reflects social identity, an associated identity standard, and appraisals that generate feelings about oneself. Analyses of SAMI’s empirical properties reveal that masking-specific emotional reactions are distinct from emotional reports related to current events and politics (discriminant validity). We also uncover evidence of predictive validity: expressed feelings about masking predict future voting more than 6 months later. We recommend SAMI to researchers interested in studying mask resistance in an increasingly polarized political climate, and the intuition behind SAMI could prove useful in other research contexts in which health decisions reflect a conscious comparison to standards held by those who share an identity or will otherwise pass judgment.
Effect of virtual reality on motor coordination in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials
Authors: Abdelhaleem Naglaa , El Wahab Manal S. Abd , Elshennawy Shorouk 
Published: March 2022

Abstract
Background
Improving motor coordination is an important prerequisite for the functional development of children with cerebral palsy (CP). Virtual reality (VR) may be efficient, interactive, adjustable and motivating physiotherapy choice for children with deficient coordination. This review aimed to identify, evaluate and formulate all the evidence concerning the efficacy of VR on motor coordination in children with CP and to compare the Physiotherapy Evidence Database (PEDro) with Cochrane Risk of Bias (RoB).

Main text
Five databases (PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Science Direct and google scholar) were systemically searched from inception up to 1st January 2019. Studies included VR intervention for children with cerebral palsy with motor incoordination. Studies methodological quality was assessed by Cochrane RoB and PEDro scale. Nineteen studies met the prespecified eligibility criteria. There was a large effect size (SMD 0.75) on fine motor coordination. However, there was a non-significant, small beneficial effect (SMD 0.15) on gross motor coordination. The association between the overall Cochrane RoB and PEDro scores was fair (r = 0.28, P value 0.248). There was a slight agreement between overall and moderate categories PEDro scores and Cochrane RoB (κ = 0.02) and κ = 0.10), respectively. However, high and low categories were moderately agreed with Cochrane RoB (κ = 0.43) and (κ = 0.46).

Conclusion
VR seems to be effective for improving fine motor coordination with questionable effect on gross motor coordination. PEDro scale is fairly correlated with Cochrane RoB, so development and validation of a more compatible quality assessment tools specific to physiotherapy trials are needed.
Impact of phototherapy type and duration on serum electrolytes and blood glucose in neonatal hyperbilirubinemia: a prospective single-center cohort study
Authors: Tosson Angie M. S. , Abdelrazek Abdelrahman A. , Yossif Rasha , Musa Noha 
Published: March 2022

Abstract
Background
Neonatal hyperbilirubinemia (NH) is among the common neonatal morbidities. Phototherapy is its most used therapeutic intervention. Different delivering systems and types are currently available. This study aimed to detect and compare the effects of the different phototherapy types on serum electrolytes and blood glucose and to study the effect of phototherapy duration on them.

Results
Five hundred healthy newborns with indirect NH were treated by different phototherapy types (conventional, light emitting diode LED, intensive) according to severity and availability. Serum sodium (Na), potassium (K), calcium (Ca), blood urea nitrogen (BUN), creatinine (Cr), and blood glucose (Glu) were measured repeatedly over 48 h of phototherapy. In this prospective cohort study, 273 (54.6%) neonates were exposed to conventional phototherapy, 145 (29.0%) to LED, and 82 (16.4%) to intensive phototherapy. A highly significant negative correlation was found between phototherapy duration and serum levels of Na, K, Ca, BUN, and Cr (p < 0.001). There was a positive correlation between phototherapy duration and blood glucose level (p = 0.005). Each type of phototherapy individually significantly affected the Na, K, Bun, Cr, and Ca levels after 48 h. Comparing the effects of the 3 different phototherapy types together, no significant differences apart from a decline in potassium level at 48 h (p = 0.043) were recorded.

Conclusions
Serum electrolytes significantly decreased during phototherapy. These changes were affected by the phototherapy duration. The type of phototherapy had only some effect on serum potassium.
Targeting Myc-driven stress vulnerability in mutant KRAS colorectal cancer
Authors: Ruan Hang , Leibowitz Brian J. , Peng Yingpeng , Shen Lin , Chen Lujia , Kuang Charlie , Schoen Robert E. , Lu Xinghua , Zhang Lin , Yu Jian 
Published: March 2022

AbstractMutant KRAS is a key driver in colorectal cancer (CRC) and promotes Myc translation and Myc-dependent stress adaptation and proliferation. Here, we report that the combination of two FDA-approved drugs Bortezomib and Everolimus (RAD001) (BR) is highly efficacious against mutant KRAS CRC cells. Mechanistically, the combination, not single agent, rapidly depletes Myc protein, not mRNA, and leads to GCN2- and p-eIF2α-dependent cell death through the activation of extrinsic and intrinsic apoptotic pathways. Cell death is selectively induced in mutant KRAS CRC cells with elevated basal Myc and p-eIF2α and is characterized by CHOP induction and transcriptional signatures in proteotoxicity, oxidative stress, metabolic inhibition, and immune activation. BR-induced p-GCN2/p-eIF2α elevation and cell death are strongly attenuated by MYC knockdown and enhanced by MYC overexpression. The BR combination is efficacious against mutant KRAS patient derived organoids (PDO) and xenografts (PDX) by inducing p-eIF2α/CHOP and cell death. Interestingly, an elevated four-gene (DDIT3, GADD45B, CRYBA4 and HSPA1L) stress signature is linked to shortened overall survival in CRC patients. These data support that Myc-dependent stress adaptation drives the progression of mutant KRAS CRC and serves as a therapeutic vulnerability, which can be targeted using dual translational inhibitors.
Factors shaping the mental health and well-being of people experiencing persistent COVID-19 symptoms or ‘long COVID’: qualitative study
Authors: Burton Alexandra , Aughterson Henry , Fancourt Daisy , Philip Keir E. J. 
Published: March 2022

BackgroundAround one in ten people who contract COVID-19 report persistent symptoms or ‘long COVID’. Impaired mental health and well-being is commonly reported, including anxiety, depression and reduced quality of life. However, there is limited in-depth research exploring why mental health and well-being are affected in people experiencing long COVID.AimsTo explore factors affecting mental health and well-being from the perspective of people with long COVID.MethodSemi-structured qualitative interviews were audio-recorded and transcribed. Data were analysed using reflexive thematic analysis. Twenty-one people with long COVID participated in the study. Participants were eligible if they self-reported a positive swab test/antibody test or one or more commonly reported COVID-19 symptoms at illness onset. and experiences of one or more long COVID symptoms ≥3 weeks following illness onset.ResultsFive themes were identified across participant accounts regarding factors affecting mental health and well-being, including symptoms causing severe disruption to daily life, lack of service and treatment options, uncertainty of illness trajectories, experiences of care and understanding from others and changes to identity.ConclusionsPeople with long COVID experience a range of factors that negatively affect their mental health and well-being. Providing patient-centred health services that integrate rapidly evolving research in this area is important, as are peer support groups and supported approaches to self-management.