bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of differentially expressed genes and signaling pathways with Candida infection by bioinformatics analysis
Authors: Zhu Guo-Dong , Xie Li-Min , Su Jian-Wen , Cao Xun-Jie , Yin Xin , Li Ya-Ping , Gao Yuan-Mei , Guo Xu-Guang
Published: March 2022

Background

Opportunistic Candida species causes severe infections when the human immune system is weakened, leading to high mortality.

Methods

In our study, bioinformatics analysis was used to study the high-throughput sequencing data of samples infected with four kinds of Candida species. And the hub genes were obtained by statistical analysis.

Results

A total of 547, 422, 415 and 405 differentially expressed genes (DEGs) of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis groups were obtained, respectively. A total of 216 DEGs were obtained after taking intersections of DEGs from the four groups. A protein–protein interaction (PPI) network was established using these 216 genes. The top 10 hub genes (FOSB, EGR1, JUNB, ATF3, EGR2, NR4A1, NR4A2, DUSP1, BTG2, and EGR3) were acquired through calculation by the cytoHubba plug-in in Cytoscape software. Validated by the sequencing data of peripheral blood, JUNB, ATF3 and EGR2 genes were  significant statistical significance.

Conclusions

In conclusion, our study demonstrated the potential pathogenic genes in Candida species and their underlying mechanisms by bioinformatic analysis methods. Further, after statistical validation, JUNB, ATF3 and EGR2 genes were attained, which may be used as potential biomarkers with Candida species infection.
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

As 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

Pullulanase 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

Protein-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

Purpose

To 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 methods

A 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.

Results

A 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.

Conclusion

The 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

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

Background

There 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.

Methods

The 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 14.0

Results

A 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%.

Conclusion

Southern 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

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

We 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

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

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

Mutant 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

Background

Around 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.

Aims

To explore factors affecting mental health and well-being from the perspective of people with long COVID.

Method

Semi-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.

Results

Five 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.

Conclusions

People 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.
Association Between Asthma and Reduced Androgen Receptor Expression in Airways
Authors: McManus Jeffrey M , Gaston Benjamin , Zein Joe , Sharifi Nima
Published: March 2022

A growing body of evidence suggests a role for androgens in asthma and asthma control. This includes a sex discordance in disease rates that changes with puberty, experiments in mice showing androgens reduce airway inflammation, and a reported association between airway androgen receptor (AR) expression and disease severity in asthma patients. We set out to determine whether airway AR expression differs between asthma patients and healthy controls. We analyzed data from 8 publicly available data sets with gene expression profiling from airway epithelial cells obtained both from asthma patients and control individuals. We found that airway AR expression was lower in asthma patients than in controls in both sexes, and that having AR expression below the median in the pooled data set was associated with substantially elevated odds of asthma vs having AR expression above the median (odds ratio 4.89; 95% CI, 3.13-7.65, P < .0001). In addition, our results suggest that whereas the association between asthma and AR expression is present in both sexes in most of the age range analyzed, the association may be absent in prepubescent children and postmenopausal women. Our results add to the existing body of evidence suggesting a role for androgens in asthma control.
Archaeology, Wage Labor, and Kinship in Rural Mexico, 1934–1974
Authors: Holley-Kline Sam
Published: March 2022

This article assesses the relationships between archaeology and wage labor in twentieth-century Mexico through an analysis of governmental payroll records from El Tajín, Veracruz. For Indigenous Totonac workers, the long-term presence of archaeological labor provided opportunities for income and social mobility in a context of dispossession and proletarianization while contributing to socioeconomic stratification. In a region where the traditional agricultural base declined during the twentieth century, participation in wage labor provided a source of regular cash income and opportunities for skill development and social mobility. Participation, however, depended on intermediaries and their kin and social networks, meaning that not all had access. The analysis suggests that state-run archaeology must be understood in practical and economic terms as well as in a regional context.
“We're Here! We're Queer! Fuck the Banks!”
Authors: Reed Alison Rose
Published: March 2022

Literalizing the metaphor of José Esteban Muñoz's famous statement, “Queerness is not yet here. . . . The here and now is a prison house,” this essay argues that the process of affectively reorienting space and minds toward abolition is a queer act. It posits that abolition and queerness overlap in their refusal to maintain faith in institutions to effect change, specifically through legal reforms that redouble the status quo while shunning broader visions of liberation. Queer abolitionist affects reorient space toward decolonial futures by challenging normative paradigms of power and its critique. In messy and imperfect ways, a queer abolitionist analysis understands love and collectivity more capaciously beyond the nuclear family unit to social relations not of domination but of transformation. By exploring the affective dimensions of queer abolition, this essay takes up the spatial and symbolic relationship between the Pride parade and the prison industrial complex. It brings together an analysis of public protest against the colonial-carceral state and prison education, specifically the Humanities Behind Bars program, in order to engage how queer affects strengthen and sustain the relationships so vital to abolitionist world making.
Delayed Presentations and Worse Outcomes After Aneurysmal Subarachnoid Hemorrhage in the Early COVID-19 Era
Authors: Akbik Feras , Yang Chris , Howard Brian M. , Grossberg Jonathan A. , Danyluk Lisa , Martin Kathleen S. , Alawieh Ali , Rindler Rima S. , Tong Frank C. , Barrow Daniel L. , Cawley C. Michael , Samuels Owen B. , Sadan Ofer
Published: March 2022

BACKGROUND:

The early phase of the COVID-19 pandemic led to significant healthcare avoidance, perhaps explaining some of the excess reported deaths that exceeded known infections. The impact of the early COVID-19 era on aneurysmal subarachnoid hemorrhage (aSAH) care remains unclear.

OBJECTIVE:

To determine the impact of the early phase of the COVID-19 pandemic on latency to presentation, neurological complications, and clinical outcomes after aSAH.

METHODS:

We performed a retrospective cohort study from March 2, 2012, to June 30, 2021, of all patients with aSAH admitted to our center. The early COVID-19 era was defined as March 2, 2020, through June 30, 2020. The pre–COVID-19 era was defined as the same interval in 2012 to 2019.

RESULTS:

Among 499 patients with aSAH, 37 presented in the early COVID-19 era. Compared with the pre–COVID-19 era patients, patients presenting during this early phase of the pandemic were more likely to delay presentation after ictus (median, interquartile range; 1 [0-4] vs 0 [0-1] days, respectively, P < .001). Radiographic-delayed cerebral ischemia (29.7% vs 10.2%, P < .001) was more common in the early COVID-19 era. In adjusted analyses, presentation in the early COVID-19 era was independently associated with increased inhospital death or hospice disposition (adjusted odds ratio 3.29 [1.02–10.65], P = .046). Both latency and adverse outcomes returned to baseline in 2021.

CONCLUSION:

aSAH in the early COVID-19 era was associated with delayed presentation, neurological complications, and worse outcomes at our center. These data highlight how healthcare avoidance may have increased morbidity and mortality in non–COVID-19-related neurosurgical disease.
Molecular contribution to embryonic aneuploidy and karyotypic complexity in initial cleavage divisions of mammalian development
Authors: Brooks Kelsey E. , Daughtry Brittany L. , Davis Brett , Yan Melissa Y. , Fei Suzanne S. , Shepherd Selma , Carbone Lucia , Chavez Shawn L.
Published: March 2022

Embryonic aneuploidy is highly complex, often leading to developmental arrest, implantation failure or spontaneous miscarriage in both natural and assisted reproduction. Despite our knowledge of mitotic mis-segregation in somatic cells, the molecular pathways regulating chromosome fidelity during the error-prone cleavage-stage of mammalian embryogenesis remain largely undefined. Using bovine embryos and live-cell fluorescent imaging, we observed frequent micro-/multi-nucleation of mis-segregated chromosomes in initial mitotic divisions that underwent unilateral inheritance, re-fused with the primary nucleus or formed a chromatin bridge with neighboring cells. A correlation between a lack of syngamy, multipolar divisions and asymmetric genome partitioning was also revealed, and single-cell DNA-seq showed propagation of primarily non-reciprocal mitotic errors. Depletion of the mitotic checkpoint protein BUB1B (also known as BUBR1) resulted in similarly abnormal nuclear structures and cell divisions, as well as chaotic aneuploidy and dysregulation of the kinase-substrate network that mediates mitotic progression, all before zygotic genome activation. This demonstrates that embryonic micronuclei sustain multiple fates, provides an explanation for blastomeres with uniparental origins, and substantiates defective checkpoints and likely other maternally derived factors as major contributors to the karyotypic complexity afflicting mammalian preimplantation development.
Svep1 stabilises developmental vascular anastomosis in reduced flow conditions
Authors: Coxam Baptiste , Collins Russell T. , Hußmann Melina , Huisman Yvonne , Meier Katja , Jung Simone , Bartels-Klein Eireen , Szymborska Anna , Finotto Lise , Helker Christian S. M. , Stainier Didier Y. R. , Schulte-Merker Stefan , Gerhardt Holger
Published: March 2022

Molecular mechanisms controlling the formation, stabilisation and maintenance of blood vessel connections remain poorly defined. Here, we identify blood flow and the large extracellular protein Svep1 as co-modulators of vessel anastomosis during developmental angiogenesis in zebrafish embryos. Both loss of Svep1 and blood flow reduction contribute to defective anastomosis of intersegmental vessels. The reduced formation and lumenisation of the dorsal longitudinal anastomotic vessel (DLAV) is associated with a compensatory increase in Vegfa/Vegfr pERK signalling, concomittant expansion of apelin-positive tip cells, but reduced expression of klf2a. Experimentally, further increasing Vegfa/Vegfr signalling can rescue the DLAV formation and lumenisation defects, whereas its inhibition dramatically exacerbates the loss of connectivity. Mechanistically, our results suggest that flow and Svep1 co-regulate the stabilisation of vascular connections, in part by modulating the Vegfa/Vegfr signalling pathway.
Αρχιτεκτονική και Μέσα Μαζικής Ενημέρωσης (ΜΜΕ)
Authors: Κοσέογλου Αικατερίνη
Published: March 2022

Η διατριβή μελετά τα αρχιτεκτονικά Μέσα Μαζικής Ενημέρωσης (ΜΜΕ) και συγκεκριμένα τα αρχιτεκτονικά έντυπα με στόχο να διερευνήσει τη σχέση τους με το γίγνεσθαι της αρχιτεκτονικής. Η διατριβή αποτελείται από δύο μέρη. Στο πρώτο μέρος αναπτύσσεται ο θεωρητικός προβληματισμός για το ρόλο των ΜΜΕ στη διαμόρφωση και εξέλιξη της αρχιτεκτονικής. Το δεύτερο μέρος της διατριβής συμπεριλαμβάνει την έρευνα πεδίου και αφορά στην καταγραφή, επεξεργασία, ερμηνεία και αξιολόγηση της κατάστασης που επικρατεί στον αρχιτεκτονικό περιοδικό τύπο στην Ελλάδα. Στο πλαίσιο αυτής της κριτικής προσέγγισης και λαμβάνοντας υπόψη την κοινωνικό-οικονομική, τεχνολογική και πολιτισμική συνθήκη της περιόδου της υπενεωτερικότητας διατυπώνονται μία σειρά από προτάσεις με στόχο τη βελτίωση και ενδυνάμωση των αρχιτεκτονικών ΜΜΕ – στην έντυπη αλλά και ψηφιακή τους μορφή- οι οποίες αναφέρονται στους αρχιτέκτονες αλλά και στον αρχιτεκτονικό τύπο.
Thyroid cancer incidences in the United Arab Emirates: a retrospective study on association with age and gender
Authors: Almansoori Asma , Busch Hauke , Bendardaf Riyad , Hamoudi Rifat
Published: March 2022

Background: Thyroid cancer is the ninth most common malignancy worldwide, but the third most common malignancy in the United Arab Emirates (UAE). To our knowledge, this is the first UAE nationwide study aimed at presenting incidence rates of thyroid cancer at the national level of UAE based upon data from the national cancer registry and GLOBOCAN.

Methods: Between 2011 and 2017, a total of 2036 thyroid cancer cases from UAE patients were registered, of which 75.3% were female and 24.7% male patients.

Results: The results showed 6.6% increase in thyroid cancer cases in the UAE from 2011 to 2017 (p < 0.001) with a rise of approximately 400 cases per year from 2011 to 2040. Age standardized rate calculations showed increase in prevalence from 1.18 in 2011 to 4.32 in 2017 but decreases in incidence from 1.05 in 2011 to 0.15 in 2017. This trend is confirmed by the predictive model showing increase in incidence from 0.15 in 2017 to 0.64 by 2040. Gender was shown to be significantly associated with thyroid cancer. The female to male ratio was significantly higher in Emirati patients (4.86:1) (p < 0.001) than expat patients (2.47:1) (p < 0.01). Interestingly, expat patients contributed to the majority of thyroid cancer cases despite having lower female to male ratio. The age at diagnosis was significantly associated with thyroid cancer (p = 0.03) with the highest frequency diagnosed at 35-39 years of age. Globally, data from the predictive model showed that Asia had the highest rate of increase per year and UAE the lowest.

Conclusions: The slight increase in thyroid cancer prevalence and incidence, together with the different female to male ratio and diagnosis at younger age warrants further investigation at the molecular level from UAE thyroid cancer patients to elucidate the molecular basis of thyroid cancer.
Methodological approaches for developing and reporting living evidence synthesis: a study protocol
Authors: Auladell-Rispau Ariadna , Bendersky Josefina , Santafe Angie , Buchanan Cecilia , Rigau Comas David , Verdugo Francisca , Ávila Camila , Alonso Pablo , Urrutia Gerard , Rada Gabriel , Rojas-Reyes María Ximena
Published: March 2022

Background: Living evidence (LE) refers to the methodological processes that permit new research findings to be continually incorporated into evidence synthesis. This approach is of great value in the resolution of relevant and rapidly changing clinical questions. To date, the methods to carry out this type of synthesis are not completely defined, and great variability is observed in the approaches used by different groups of authors.

Objective: To identify, evaluate and summarise the current methods used for living evidence synthesis

Methods: We will conduct a methodological study based on a systematic literature search to identify any type of evidence synthesis such as systematic reviews, network metanalyses and overviews that used “living evidence synthesis” as part of their methods. The search will be conducted in Medline (via PubMed) and Epistemonikos databases. Additionally, we will search websites of the organisations publishing any living evidence synthesis retrieved in the two databases, in order to identify unpublished subsequent reports. Two reviewers will independently assess each article against the selection criteria, extract data on methods and procedures, and assess the methodological quality of each publication. Data will be analysed descriptively.
Promotion of data sharing needs more than an emergency: An analysis of trends across clinical trials registered on the International Clinical Trials Registry Platform
Authors: Merson Laura , Ndwandwe Duduzile , Malinga Thobile , Paparella Giuseppe , Oneil Kwame , Karam Ghassan , Terry Robert F.
Published: March 2022

BACKGROUND: A growing body of evidence shows that sharing health research data with other researchers for secondary analyses can contribute to better health. This is especially important in the context of a public health emergency when stopping a pandemic depends on accelerating science.

METHODS: We analysed the information on data sharing collected by the 18 clinical trial registries included in the WHO International Clinical Trials Registry Platform (ICTRP) to understand the reporting of data sharing plans and which studies were and were not planning to share data. Data on sponsor and funder organisations, country of recruitment, registry, and condition of study were standardised to compare the sharing of information and data across these facets. This represents the first ever comprehensive study of the complete data set contained in ICTRP.

RESULTS: Across 132,545 studies registered between January 2019 and December 2020, 11.2% of studies stated that individual patient data (IPD) would be shared. Plans to share IPD varied across the 18 contributing registries– information on data sharing was missing in >95% of study records across 7/18 registries. In the 26,851 (20.3%) studies that were funded or sponsored by a commercial entity, intention to share IPD was similar to those that were not (11.5% vs 11.2%). Intention to share IPD was most common in studies recruiting across both high-income and low- or middle-income countries (21.4%) and in those recruiting in Sub-Saharan Africa (50.3%). Studies of COVID-19 had similar levels of data sharing to studies of other non-pandemic diseases in 2020 (13.7% vs 11.7%).

CONCLUSIONS: Rates of planned IPD sharing vary between clinical trial registries and economic regions, and are similar whether commercial or non-commercial agencies are involved. Despite many calls to action, plans to share IPD have not increased significantly and remain below 14% for diseases causing public health emergencies.
Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2
Authors: Eales Oliver , Walters Caroline E. , Wang Haowei , Haw David , Ainslie Kylie E. C. , Atchison Christina J. , Page Andrew J. , Prosolek Sophie , Trotter Alexander J. , Le Viet Thanh , Alikhan Nabil-Fareed , Jackson Leigh M. , Ludden Catherine ,   COVID-19 Genomics UK Consortium, Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul , Riley Steven
Published: March 2022

Background:The REal-time Assessment of Community Transmission-1 (REACT-1) study has provided unbiased estimates of swab-positivity in England approximately monthly since May 2020 using RT-PCR testing of self-administered throat and nose swabs. However, estimating infection incidence requires an understanding of the persistence of RT-PCR swab-positivity in the community.

Methods:During round 8 of REACT-1 from 6 January to 22 January 2021, we collected up to two additional swabs from 896 initially RT-PCR positive individuals approximately 6 and 9 days after their initial swab.

Results:Test sensitivity and duration of positivity were estimated using an exponential decay model, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. A P-spline model was used to estimate infection incidence for the entire duration of the REACT-1 study. REACT-1 test sensitivity was estimated at 0.79 (0.77, 0.81) with median duration of positivity at 9.7 (8.9, 10.6) days. We found greater duration of positivity in those exhibiting symptoms, with low N-gene Ct values, or infected with the Alpha variant. Test sensitivity was found to be higher for those who were pre-symptomatic or with low N-gene Ct values. Compared to swab-positivity, our estimates of infection incidence included sharper features with evident transient increases around the time of changes in social distancing measures.

Conclusions:These results validate previous efforts to estimate incidence of SARS-CoV-2 from swab-positivity data and provide a reliable means to obtain community infection estimates to inform policy response.
ECONOMIC ASPECTS OF THE ECOLOGICAL APPROACH TO THE DEVELOPMENT OF AGRICULTURE AT THE PRESENT STAGE
Authors: Suchkov Dmitry K. , Sorgutov Ilya V. , Gavrilieva Nadezhda K. , Grigoriev Alexander V.
Published: March 2022

The economic aspects of the development of the agro-industrial complex at the present stage play a significant role in shaping the well-being of any country, since the factor of seasonality and the need to allocate subsidies to support most agricultural enterprises often negatively affect the prospects for the development of the industry in question. At the same time, it should be noted that agro-industrial companies spend significant funds on recultivation and restoration of lands damaged by regular application of chemical fertilizers. Also, various biosystems are being destroyed, without which the implementation of various activities in the agro-industrial complex will be impossible: water resources are being depleted, representatives of fauna are dying, the structure of individual ecological networks is being disrupted. For this reason, the application of an ecological approach in the process of forming an economic strategy for the development of agriculture at the present stage becomes necessary, since if the status quo is maintained, the negative situation in agriculture may worsen in the next few years. For this reason, we consider it necessary to implement the main provisions of the Concept of Sustainable Development in the process of planning and implementing various areas of economic and production activities in the agricultural sector, since relying on the postulates declared by the Concept will expand the horizons of the industry’s development, improve the quality and volume of products produced and reduce its negative impact on the environment, thereby preserving the ecological balance in nature.
SOMATOFORM DYSFUNCTION OF THE AUTONOMIC NERVOUS SYSTEM IN ADOLESCENTS: VEGETATIVE HOMEOSTASIS AND ERYTHROCYTE MEMBRANE REACTIVITY
Authors: Zaitseva Zhanna G. , Zaitseva Olga I. , Kolodyazhnaya Tatyana A.
Published: March 2022

Aim. To study autonomic homeostasis and reactivity of erythrocyte membranes to bioregulators of the autonomic nervous system in adolescents with somatoform dysfunction of the autonomic nervous system to predict the course of the disease and assess adaptive capabilities.

Materials and methods. Clinical, instrumental and laboratory examination of adolescents with somatoform dysfunction of the autonomic nervous system and healthy adolescents was carried out.

Results. In adolescents with somatoform dysfunction of the autonomic nervous system, dysregulatory types of autonomic response were revealed at the level of erythrocyte membranes. Significant biophysical risk factors for the paroxysmal course of the disease have been identified: low peak and rate fluorescence values with acetylcholine, as well as low peak fluorescence values with adrenaline.

Conclusion. Identification of autonomic dysregulation at the level of cell membranes in adolescents with somatoform dysfunction of the autonomic nervous system is an important factor determining the course of the disease, as well as the adaptive capabilities of the adolescent’s body. Establishment of significant membrane risk factors for a complicated course of the disease is necessary for a personalized approach to the implementation of therapeutic and prophylactic measures.
AGE-DEPENDENT VARIABILITY OF THE DYNAMICS OF LINEAR GROWTH OF SALIX TRIANDRA SHOOTS
Authors: Afonin Alexey A.
Published: March 2022

Salix triandra (almond willow) is an established crop, grown for basket-making materials. This species is also used for a wide range of environmental projects. The paper aimed to comparative analysis of the seasonal dynamics of linear growth of shoots in S. triandra clones on stools of different ages. The object of the study is a model inbred-clonal population of S. triandra. Our study analyzed the growing annual shoots on saplings from cuttings. To obtain the material, one- and two-year-old stools of four clones were used. The observations were carried out in the conditions of the vegetative period in the year 2021. The development of shoots occurred in conditions of extremely excessive atmospheric moisture at the beginning of the growing season. The study also assessed the impact of ruderal vegetation.

As a result of our observations, it was found that the length of shoots on annual stools reached 210-220 cm, on biennial stools – 300-340 cm. The average daily increment of shoots on annual stools was 2.01±0.052 cm/day (with a maximum of 3.8-4.4 cm/day), on biennial stools – 2.88±0.069 cm/day (with a maximum of 5.0-6.1 cm/day). The root mean square amplitude of oscillation in the daily growth of shoots on annual stools was 0.79 cm/day, on biennial stools – 1.34 cm/day. The results showed that, regardless of the age of the stool, there is a cyclic development of shoots, which is due to the alternation of the maximum and minimum daily growth. The greatest degree of synchronization of maximum and minimum values of daily shoots increment in spring and early summer is revealed. A clone has been identified that gives consistently high increment of shoots. It is recommended to use such clones to create sustainable and multifunctional crops of almond willow.