bluuebunny/crossref_metadata_2025 huggingface dataset:
A Risk-Benefit Analysis of Increasing Surgical Invasiveness Relative to Frailty Status in Adult Spinal Deformity Surgery
Authors: Passias Peter G. , Brown Avery E. , Bortz Cole , Pierce Katherine , Alas Haddy , Ahmad Waleed , Passfall Lara , Kummer Nicholas , Krol Oscar , Lafage Renaud , Lafage Virginie , Burton Douglas , Hart Robert , Anand Neel , Mundis Gregory , Neuman Brian , Line Breton , Shaffrey Christopher , Klineberg Eric , Smith Justin , Ames Christopher , Schwab Frank J. , Bess Shay
Published: February 2021

Study Design.

Retrospective review of a prospectively enrolled multicenter Adult Spinal Deformity (ASD) database.

Objective.

Investigate invasiveness and outcomes of ASD surgery by frailty state.

Summary of Background Data.

The ASD Invasiveness Index incorporates deformity-specific components to assess correction magnitude. Intersections of invasiveness, surgical outcomes, and frailty state are understudied.

Methods.

ASD patients with baseline and 3-year (3Y) data were included. Logistic regression analyzed the relationship between increasing invasiveness and major complications or reoperations and meeting minimal clinically important differences (MCID) for health-related quality-of-life measures at 3Y. Decision tree analysis assessed invasiveness risk-benefit cutoff points, above which experiencing complications or reoperations and not reaching MCID were higher. Significance was set to P < 0.05.

Results.

Overall, 195 of 322 patients were included. Baseline demographics: age 59.9 ± 14.4, 75% female, BMI 27.8 ± 6.2, mean Charlson Comorbidity Index: 1.7 ± 1.7. Surgical information: 61% osteotomy, 52% decompression, 11.0 ± 4.1 levels fused. There were 98 not frail (NF), 65 frail (F), and 30 severely frail (SF) patients. Relationships were found between increasing invasiveness and experiencing a major complication or reoperation for the entire cohort and by frailty group (all P < 0.05). Defining a favorable outcome as no major complications or reoperation and meeting MCID in any health-related quality of life at 3Y established an invasiveness cutoff of 63.9. Patients below this threshold were 1.8[1.38–2.35] (P < 0.001) times more likely to achieve favorable outcome. For NF patients, the cutoff was 79.3 (2.11[1.39–3.20] (P < 0.001), 111 for F (2.62 [1.70–4.06] (P < 0.001), and 53.3 for SF (2.35[0.78–7.13] (P = 0.13).

Conclusion.

Increasing invasiveness is associated with increased odds of major complications and reoperations. Risk-benefit cutoffs for successful outcomes were 79.3 for NF, 111 for F, and 53.3 for SF patients. Above these, increasing invasiveness has increasing risk of major complications or reoperations and not meeting MCID at 3Y.

Level of Evidence: 3
Subaxial Spine Fractures
Authors: Fröjd Révész David , Norell Andrea , Charalampidis Anastasios , Endler Peter , Gerdhem Paul
Published: February 2021

Study Design.

Observational study on prospectively collected data.

Objectives.

The aim of this study was to compare long-term patient-reported outcomes and complications after anterior or posterior cervical spine surgery for subaxial fractures.

Summary of Background Data.

There is no consensus in the literature regarding the optimal surgical approach when treating spine fractures in the subaxial region.

Methods.

A total of 200 individuals who had been treated with either anterior or posterior surgery due to a subaxial single segment, or single vertebra, injury between 2006 and 2016 and had at least 1 year follow-up were identified in the Swedish Spine register. Cases were matched 1:1 for age (±5 years). Outcomes were Neck Disability Index (NDI) and EQ-5D-3L, and reoperations, mortality, and surgeon- and patient-reported wound complications within 90 days. t Tests and χ
2 tests were used statistical comparisons.

Results.

At follow-up, NDI was 23 (21) in the anterior group and 29 (21) in the posterior group (P = 0.07). EQ-5D-3L index was 0.62 (0.37) in the anterior group and 0.54 (0.39) in the posterior group (P = 0.13). Patient satisfaction was higher in the anterior group (89% vs. 73%, P = 0.03). No deaths occurred within the first 90 days after surgery, six individuals in the anterior group and three individuals in the posterior group were reoperated (P = 0.31), and five individuals in the anterior group and 24 in the posterior group suffered a wound infection (P < 0.001).

Conclusion.

Anterior surgery and posterior surgery were associated with similar neck disability and general quality of life at follow-up, whereas anterior surgery was associated with higher patient satisfaction and lower infection rates.

Level of Evidence: 3
Determining Average Linear Dimension and Volume of Korean Lungs for Lung Phantom Construction
Authors: Yang Sook , Kim Jeongin , Choi Seung Jin , Lee Kyung Won
Published: February 2021

The purpose of this study was to determine the average size and volume of lungs and to simulate the morphology of internal organs for the development of a Korean adult lung phantom. The body-size data of 2,195 males and 2,293 females aged between 20 and 60 y were included to calculate the average physical dimensions. Two hundred datasets of computed tomography corresponding to the average physique range were collected to measure the average linear dimensions (the length of x, y, and z-axis) of lungs. One set of lung CT images was finally obtained and converted to three-dimensional (3D) format. To confirm the validity of the new lung model, physical lung phantoms were constructed using International Commission on Radiation Units and Measurements (ICRU) density and similar density to what was obtained from the human CT image and then compared with the Lawrence Livermore National Laboratory (LLNL) phantom. The mean size of the chest width and thickness was 31.8 ± 2.8 and 21.4 ± 1.9 cm for males and 28.0 ± 1.6 cm and 19.4 ± 2.0 cm for females, respectively. The standard deviation of the lung dimension in this group was ± 3.0 cm in length, ± 0.8 cm in width, and ± 2.27 cm in depth. The two modified lung phantoms showed highly accurate geometry and linear attenuation coefficient vs. those of the LLNL phantom. The difference in CT number was ± 2% HU for the LLNL phantom and ± 4% HU for the human CT image based on a CT examination conducted using the chest CT protocol. Moreover, both lungs weighed 734 g to 1,246 g, within the range of the reference value of the ICRU report. These results demonstrate that a new lung model based on average linear dimension measurement in a group with average physique simulated the features and physical properties of real human lungs and facilitated further studies for phantom construction.
Efficacy and Safety of Ultrasound Cycloplasty for Refractory Glaucoma: A 3-Year Study
Authors: Rouland Jean-François , Aptel Florent
Published: February 2021

Precis:

Ultrasound cycloplasty (UCP) treatment using high-intensity focused ultrasound is an effective and safe therapy to reduce intraocular pressure (IOP) in patients with refractory glaucoma over a 3-year period.

Purpose:

The purpose of this study was to evaluate the 3-year efficacy and safety of UCP in patients with refractory glaucoma.

Patients and Methods:

In all, 104 patients with refractory glaucoma recruited from 2 university hospitals underwent UCP. Examinations were performed 7 days, 1 week, 1, 3, 6, 12, 24, and 36 months after the UCP procedure. Primary outcomes were therapeutic success at 3 years (IOP reduction from baseline ≥20% and IOP >5 mm Hg without other surgical procedures) and vision-threatening complications. Secondary outcomes included mean IOP change from baseline at each follow-up visit, medication use, complications, and subsequent UCP and/or other postsurgical interventions.

Results:

At 3 years post-UCP, the therapeutic success rate was 55%. For 75% of the patients, results were obtained with only one procedure. For the overall study population, IOP was reduced significantly (P<0.005) from 27.6±8.9 mm Hg (n=3.0 topical hypotensive medication) to 17.0±6.8 mm Hg at 36 months (n=2.8 topical hypotensive medication) (33% reduction). For the success patients, the IOP was initially 29.3±8.8 mm Hg (n=3.0 topical hypotensive medication) and 15.6±4.3 mm Hg at 36 months (n=2.8 topical hypotensive medication) (43% reduction). The rate of complications was low and there were no cases of phthisis.

Conclusion:

The UCP procedure was efficacious with few complications and should be considered as an alternative to other IOP-lowering therapies including laser cyclocoagulation in patients with refractory glaucoma.
Efficacy and Safety of the Susanna Glaucoma Drainage Device After 1 Year of Follow-up
Authors: Susanna Fernanda N. , Susanna Bianca N. , Susanna Carolina N. , Nicolela Marcelo T. , Susanna Remo
Published: February 2021

Precis:

This study found a rate of failure of 13.6% of the new Susanna Glaucoma Drainage Device (SGDD) after 1 year of follow-up. Severe complications occurred in 1 patient (4.5%).

Purpose:

The purpose of this study was to determine the success and complications rates of the SGDD implant in refractory glaucoma.

Patients and Methods:

This is a retrospective study. Medical records from all consecutive refractory glaucoma patients (failed trabeculectomies with the use of adjunctive mitomycin) followed in a private clinical practice were included in the study. All patients had undergone SGDD implant surgery from September 2016 to July 2019 were included. All surgeries were done by the same surgeon (R.S.). Primary outcome was surgical failure, defined as intraocular pressure (IOP) >18 mm Hg and/or <20% IOP reduction from baseline, IOP<5 mm Hg, reoperation for glaucoma, need of implant removal or loss of light perception vision. Secondary outcomes included mean IOP, use of supplemental medical therapy, and complications.

Results:

In all, 22 eyes were analyzed. Mean patient age was 63±15 years (range: 27 to 87 y). Mean IOP decreased from 23±7 to 11±8 mm Hg (P<0.001, paired t test) at an average of 18±9 months after the tube implant. The mean SD number of glaucoma medications was reduced from 3.3±1 to 1.5±1.2 at the last postoperative visit (P<0.01, paired t test). No early postoperative complications occurred. There was 1 case of late persistent hypotony in a patient with previous endocyclophotocoagulation that was solved with tube ligature with silk 8-0. Failure because of high IOP occurred in 2 cases. There was no extrusion or erosion of the tube and the plate.

Conclusion:

The SGDD presented a 13.6% failure rate (86.4% success rate) with very few complications, being an efficient and safe alternative for refractory glaucoma.
Weekly Email Reminders Increase Nursing Students' Use of Empathic Communication
Authors: Varagona Lynn , Myers Rachel , Wilson Astrid
Published: February 2021

Background

Empathic communication has numerous patient benefits, yet many nurses do not possess or utilize empathic communication skills.

Purpose

This study compared the efficacy of 2 low-cost, low-resource-intensive interventions to increase nursing students' use of empathic communication.

Methods

The study was a randomized controlled trial with a pretest, posttest, and 3-month follow-up test. Participants were assigned to 1 of 4 groups: weekly empathic communication email reminders, an empathic communication quick reference guide, both, or neither.

Results

All groups showed a significant increase in empathic communication between the pretest and posttest. The group that received emails only showed a significant increase above and beyond the control group. None of the groups significantly increased or decreased their empathic communication between the posttest and 3-month follow-up test.

Conclusions

Weekly empathic communication email reminders can increase nursing students' use of empathic communication above and beyond traditional lectures and class activities.
Comparing Interprofessional Socialization in Mixed-Discipline and Nursing Student–Only Cohorts
Authors: Groom Kara K. , Frenn Marilyn , Breakwell Susan , Melchert Timothy , Garnier-Villarreal Mauricio
Published: February 2021

Background

A challenge to substantiating the value of interprofessional education (IPE) has been the limited number of studies that assess the effectiveness of IPE interventions compared with education interventions in which professions were learning separately from one another.

Purpose

The purpose was to compare interprofessional socialization (IS) in mixed-discipline and single-discipline–only student cohorts to determine if mixed-discipline cohorts demonstrate greater improvement in IS compared with single-discipline cohorts.

Methods

Interprofessional socialization was measured using the Interprofessional Socialization and Valuing Scale in 166 university students who completed a semester-long online palliative care course.

Results

Statistically significant increases in IS were seen with all participants, both those in discipline-specific as well as mixed-discipline cohorts and in all IS subscales. No difference was observed between a cohort of nursing student–only learners versus a cohort of mixed-discipline students.

Conclusion

The study demonstrates that IS can be significantly increased whether students participate with single discipline peers or in mixed-discipline settings.
Clinicopathologic and Molecular Cytogenetic Analysis of 8 Cases With Uterine Cervical Ewing Sarcoma
Authors: Cheng Yufan , Bai Qianming , Wu Bin , Chang Bin , Bi Rui , Yang Wentao , Wang Jian , Tu Xiaoyu
Published: February 2021

Ewing sarcoma (ES) is a highly malignant tumor that rarely occurs in the uterine cervix. Herein, we report 8 cases with ES arising primarily in the uterine cervix by focusing on clinicopathologic and molecular cytogenetic features and differential diagnoses. Eight cases of cervical ES were diagnosed between February, 2012, and September, 2018. The age of patients ranged from 13 to 47 years. Abnormal vaginal bleeding and lower abdominal pain were the most common symptoms. Histologically, the tumor was composed of uniform, round, and oval cells with a narrow rim of eosinophilic cytoplasm. Fibrous septa were observed between tumor cell nests. The tumors showed brisk mitotic activity and areas of coagulative necrosis. According to immunohistochemical studies, 50% (4/8) of the cases were positive for cytokeratin (AE1/AE3), and 87.5% (7/8) were positive for synaptophysin, which resulted in a diagnostic confusion with small cell carcinoma, primarily when dealing with small cervical biopsies. Molecular testing demonstrated the rearrangement of the EWSR1 gene in all of the 8 cases, which confirmed the diagnosis of ES. Although rare, ES should be considered as indicators of cervical small round cell neoplasms. Molecular analysis may greatly contribute to the final diagnosis of ES occurring in this unusual location.
The Calcium Versus Hemorrhage Trial
Authors: Schellingerhout Dawid , Jacobsen Megan , Le Roux Lucia , Johnson Jason , Baladandayuthapani Veera , Hwang Ken-Ping , Hazle John , Schomer Donald , Cody Dianna
Published: February 2021

Purpose

Chronic susceptibility lesions in the brain can be either hemorrhagic (potentially dangerous) or calcific (usually not dangerous) but are difficult to discriminate on routine imaging. We proposed to develop quantitative diagnostic criteria for single-energy computed tomography (SECT), dual-energy computed tomography (DECT), and quantitative susceptibility mapping (QSM) to distinguish hemorrhage from calcium.

Materials and Methods

Patients with positive susceptibility lesions on routine T2*-weighted magnetic resonance of the brain were recruited into this prospective imaging clinical trial, under institutional review board approval and with informed consent. The SECT, DECT, and QSM images were obtained, the lesions were identified, and the regions of interest were defined, with the mean values recorded. Criteria for quantitative interpretation were developed on the first 50 patients, and then applied to the next 45 patients. Contingency tables, scatter plots, and McNemar test were applied to compare classifiers.

Results

There were 95 evaluable patients, divided into a training set of 50 patients (328 lesions) and a validation set of 45 patients (281 lesions). We found the following classifiers to best differentiate hemorrhagic from calcific lesions: less than 68 Hounsfield units for SECT, calcium level of less than 15 mg/mL (material decomposition value) for DECT, and greater than 38 ppb for QSM. There was general mutual agreement among the proposed criteria. The proposed criteria outperformed the current published criteria.

Conclusions

We provide the updated criteria for the classification of chronic positive susceptibility brain lesions as hemorrhagic versus calcific for each major clinically available imaging modality. These proposed criteria have greater internal consistency than the current criteria and should likely replace it as gold standard.
Infectious Complications in Tocilizumab-treated Kidney Transplant Recipients
Authors: Sethi Supreet , Peng Alice , Najjar Reiad , Vo Ashley , Jordan Stanley C. , Huang Edmund
Published: February 2021

Background.

Tocilizumab is an interleukin-6 receptor antagonist recently described as a promising treatment for antibody-mediated rejection. We compared infectious complications among tocilizumab-treated kidney transplant patients with those receiving intravenous immunoglobulin (IVIG)/rituximab.

Methods.

Infections occurring among 148 kidney recipients treated with tocilizumab 8 mg/kg IV monthly (n = 83) or IVIG/rituximab (n = 65) for donor-specific antibodies and antibody-mediated rejection through 1 year after treatment cessation were reviewed. Incidence rates of infections were compared using Poisson regression.

Results.

There were 106 infections observed over 190.1 person-years, yielding an incidence rate of 558 infections/1000 patient-years. A lower incidence rate of infections was observed among tocilizumab-treated compared with IVIG/rituximab-treated patients (463 infections/1000 patient-years versus 730 infections/1000 patient-years; P = 0.02). Twenty-five of 49 infections (51%) in the IVIG/rituximab group required hospitalization compared with 31 of 57 (54%; P = 0.85) in the tocilizumab group. There were no infection-related deaths in either group. Urinary tract infections and pneumonia were the most common types of infections, whereas gastrointestinal, blood, skin/soft tissue, viral, and fungal infections were less common. On multivariable Poisson regression, there was a lower incidence rate of infections associated with tocilizumab compared with IVIG/rituximab (incidence rate ratio, 0.63; 95% confidence interval, 0.43-0.93).

Conclusions.

Among kidney transplant patients treated with tocilizumab, there was no excess risk of infections compared with standard therapy with IVIG/rituximab.
Donor-derived Cell-free DNA in Solid-organ Transplant Diagnostics: Indications, Limitations, and Future Directions
Authors: Kataria Ashish , Kumar Dhiren , Gupta Gaurav
Published: February 2021

The last few years have seen an explosion in clinical research focusing on the use of donor-derived cell-free DNA (dd-cfDNA) in solid-organ transplants (SOT). Although most of the literature published so far focuses on kidney transplants, there are several recent as well as ongoing research studies on heart, lung, pancreas, and liver transplants. Though initially studied as a noninvasive means of identifying subclinical or acute rejection in SOT, it is rapidly becoming clear that instead of being a specific marker for allograft rejection, dd-cfDNA is more appropriately described as a marker of severe injury, although the most common cause of this injury is allograft rejection. Multiple studies in kidney transplants have shown that although sensitivity for the diagnosis of antibody-mediated rejection is excellent, it is less so for T-cell–mediated rejection. It is possible that combining dd-cfDNA with other novel urine- or blood-based biomarkers may increase the sensitivity for the diagnosis of rejection. Irrespective of the cause, though, elevated dd-cfDNA seems to portend adverse allograft prognosis and formation of de novo donor-specific antibody. Although current data do not lend themselves to a clear conclusion, ongoing studies may reveal the utility of serial surveillance for the management of SOT as following levels of dd-cfDNA over time may provide windows of opportunity to intervene early and before irreversible allograft injury. Finally, cost-effectiveness studies will be needed to guide the ideal incorporation of dd-cfDNA into routine clinical practice.
Association Between Treatment of Secondary Hyperparathyroidism and Posttransplant Outcomes
Authors: Mathur Aarti , Sutton Whitney , Ahn JiYoon B. , Prescott Jason D. , Zeiger Martha A. , Segev Dorry L. , McAdams-DeMarco Mara
Published: February 2021

Background.

Secondary hyperparathyroidism (SHPT) affects nearly all patients on maintenance dialysis therapy. SHPT treatment options have considerably evolved over the past 2 decades but vary in degree of improvement in SHPT. Therefore, we hypothesize that the risks of adverse outcomes after kidney transplantation (KT) may differ by SHPT treatment.

Methods.

Using the Scientific Registry of Transplant Recipients and Medicare claims data, we identified 5094 adults (age ≥18 y) treated with cinacalcet or parathyroidectomy for SHPT before receiving KT between 2007 and 2016. We quantified the association between SHPT treatment and delayed graft function and acute rejection using adjusted logistic models and tertiary hyperparathyroidism (THPT), graft failure, and death using adjusted Cox proportional hazards; we tested whether these associations differed by patient characteristics.

Results.

Of 5094 KT recipients who were treated for SHPT while on dialysis, 228 (4.5%) underwent parathyroidectomy, and 4866 (95.5%) received cinacalcet. There was no association between treatment of SHPT and posttransplant delayed graft function, graft failure, or death. However, compared with patients treated with cinacalcet, those treated with parathyroidectomy had a lower risk of developing THPT (adjusted hazard ratio, 0.56; 95% confidence interval, 0.35-0.89) post-KT. Furthermore, this risk differed by dialysis vintage (P
interaction = 0.039). Among patients on maintenance dialysis therapy for ≥3 y before KT (n = 3477, 68.3%), the risk of developing THPT was lower when treated with parathyroidectomy (adjusted hazard ratio, 0.43; 95% confidence interval, 0.24-0.79).

Conclusions.

Parathyroidectomy should be considered as treatment for SHPT, especially in KT candidates on maintenance dialysis for ≥3 y. Additionally, patients treated with cinacalcet for SHPT should undergo close surveillance for development of tertiary hyperparathyroidism post-KT.
Flavobacterium lotistagni sp. nov. and Flavobacterium celericrescens sp. nov., isolated from freshwater habitats
Authors: Wu Jia-Hong , You Ya-Xiu , Young Chiu-Chung , Kwon Soon-Wo , Chen Wen-Ming
Published: February 2021

This study presents taxonomic descriptions of strains CYK-4T and TWA-26T isolated from freshwater habitats in Taiwan. Both strains were Gram-stain-negative, strictly aerobic, motile by gliding and rod-shaped. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that both strains belonged to the genus

Flavobacterium

. Analysis of 16S rRNA gene sequences showed that strains CYK-4T and TWA-26T shared 92.7 % sequence similarity and were most closely related to

Flavobacterium ovatum

W201ET (95.6 %) and

Flavobacterium aquaticum

JC164T (96.7 %), respectively. Both strains shared common chemotaxonomic characteristics comprising MK-6 as the main isoprenoid quinone, iso-C15 : 0 and iso-C15 : 1 G as the predominant fatty acids, phosphatidylethanolamine as the principal polar lipid, and homospermidine as the major polyamine. The DNA G+C contents of strains CYK-4T and TWA-26T were 41.5 and 31.8 mol%, respectively. The average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization values between these two novel isolates and their closest relatives were below the cut-off values of 95–96, 90 and 70 %, respectively, used for species demarcation. On the basis of phenotypic and genotypic properties and phylogenetic inference, both strains should be classified as novel species within the genus

Flavobacterium

, for which the names Flavobacterium lotistagni sp. nov. (type strain CYK-4T=BCRC 81192T=LMG 31330T) and Flavobacterium celericrescens sp. nov. (type strain TWA-26T=BCRC 81200T=LMG 31333T) are proposed.
Surveillance of invasive meningococcal disease in the south of Brazil: considerations of immunization programme
Authors: Silveira Marcelle Moura , Crespo da Silva Pedro Augusto , Conrad Neida Lucia , Oliveira Thaís Larré , Hartwig Daiane Drawanz , Trotter Caroline
Published: February 2021

Invasive meningococcal disease (IMD) is a major cause of meningitis and septicaemia worldwide. The switches in serogroup predominance contribute to the unpredictable nature of the disease with significant health impacts. The aim of this study was to determine the epidemiological profile of IMD in Rio Grande do Sul, Santa Catarina and Paraná, three states in the south of Brazil. All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2015 and 2019 were analysed. Proportions of serogroup and incidence by age were calculated. A total of 17 894 cases of IMD were reported during this period. Of these, 9029 cases (50 %) were due to serogroup C. Furthermore, serogroup W was responsible for almost half of the cases among children younger than 5 years old during 2017 and 2018, with an overall incidence of 33.3 cases per 100 000 infants. Despite the reduction in serogroup C after the introduction of meningococcal C conjugate vaccine into a childhood immunization programme in Brazil, it remains a significant healthcare issue in the south of the country. Changes in disease epidemiology were observed and serogroup W was the most common among children below 5 years of age in 2017 and 2018. Although future cost-effectiveness studies are necessary, our results could have future implications for meningococcal vaccination programmes.
An arabinose-induced enhancement of asexual reproduction and concomitant changes in metabolic state in the filamentous fungus Bipolaris maydis
Authors: Yoshida Hiroshi , Tanaka Chihiro
Published: February 2021

l-Arabinose, a major constituent pentose of plant cell-wall polysaccharides, has been suggested to be a less preferred carbon source for fungi but to be a potential signalling molecule that can cause distinct genome-wide transcriptional changes in fungal cells. Here, we explore the possibility that this unique pentose influences the morphological characteristics of the phytopathogenic fungus Bipolaris maydis strain HITO7711. When grown on plate media under different sugar conditions, the mycelial dry weight of cultures on l-arabinose was as low as that with no sugar, suggesting that l-arabinose does not substantially contribute to vegetative growth. However, the intensity of conidiation on l-arabinose was comparable to or even higher than that on d-glucose and on d-xylose, in contrast to the poor conidiation under the no-sugar condition. To explore the physiological basis of the passive growth and active conidiation on l-arabinose, we next investigated cellular responses of the fungus to these sugar conditions. Transcriptional analysis of genes related to carbohydrate metabolism showed that l-arabinose stimulates carbohydrate utilization through the hexose monophosphate shunt (HMP shunt), a catabolic pathway parallel to glycolysis and which participates in the generation of the reducing agent NADPH (the reduced form of nicotinamide adenine dinucleotide phosphate). Then, the HMP shunt was impaired by disrupting the related gene BmZwf1, which encodes glucose-6-phosphate dehydrogenase in this fungus. The resulting mutants on l-arabinose showed remarkably decreased conidiation, but a conversely increased mycelial dry weight compared with the wild-type. Our study demonstrates that l-arabinose acts to enhance resource allocation to asexual reproduction in B. maydis HITO7711 at the cost of vegetative growth, and suggests that this is mediated by the concomitant stimulation of the HMP shunt.
Ribosome hibernation: a new molecular framework for targeting nonreplicating persisters of mycobacteria
Authors: Li Yunlong , Sharma Manjuli R. , Koripella Ravi K. , Banavali Nilesh K. , Agrawal Rajendra K. , Ojha Anil K.
Published: February 2021

Treatment of tuberculosis requires a multi-drug regimen administered for at least 6 months. The long-term chemotherapy is attributed in part to a minor subpopulation of nonreplicatingMycobacterium tuberculosiscells that exhibit phenotypic tolerance to antibiotics. The origins of these cells in infected hosts remain unclear. Here we discuss some recent evidence supporting the hypothesis that hibernation of ribosomes inM. tuberculosis,induced by zinc starvation, could be one of the primary mechanisms driving the development of nonreplicating persisters in hosts. We further analyse inconsistencies in previously reported studies to clarify the molecular principles underlying mycobacterial ribosome hibernation.
Emergence of SARS-CoV-2 stains harbouring the signature mutations of both A2a and A3 clade
Authors: Sarkar Rakesh , Banerjee Anindita , Dutta Shanta , Chawla-Sarkar Mamta
Published: February 2021

SARS-CoV-2 strains with both high transmissibility and potential to cause asymptomatic infection is expected to gain selective advantage over other circulating strains having either high transmissibility or ability to trigger asymptomatic infection. The D614G mutation in spike glycoprotein, the characteristic mutation A2a clade, has been associated with high transmissibility, whereas the A3 clade specific mutation L37F in NSP6 protein has been linked with asymptomatic infection. In this study, we performed a comprehensive mutational analysis of 3,77,129 SARS-CoV-2 genomes collected during January, 2020 to December, 2020 from all across the world for the presence of D614G and L37F mutations. Out of 3,77,129 SARS-CoV-2 strains analysed, 14, 598 (3.87%) were found to harbour both the D614G and L37F mutations. Majority of these double mutant SARS-CoV-2 strains were identified in Europe (11097) followed by North America (1915), Asia (980), Oceania (242), Africa (219), and South America (145). Geographical root surveillance revealed their first emergence during February-March in all the six continents. Temporal prevalence analysis from February, 2020 to December, 2020 showed a gradual upsurge in their frequencies worldwide, which strongly demonstrated the adaptive selection of these double mutants. Evolutionary analysis depicted that these double mutants emerged as a new clade in the dendrogram (named as A2a/3), and were sub-divided into four distinct clusters (Cluster I, II, III and IV) according to different sets of coexisting mutations. The frequency distribution pattern showed the global predominance of cluster III (41.42%), followed by cluster IV (23.31%), cluster II (21.02%) and cluster I (14.25%). Overall, our study highlighted the emergence of a unique phylogenetic clade encompassing the double-mutant SARS-CoV-2 strains which may provide a fitness advantage during course of virus evolution.
A Cross-Sectional Study Evaluating Tick-borne Encephalitis Vaccine Uptake and Timeliness Among Adults in Switzerland
Authors: Zens Kyra D. , Baroutsou Vasiliki , Sinniger Philipp , Lang Phung
Published: February 2021

Objectives

The goal of this study was to evaluate timeliness of Tick-borne Encephalitis vaccination uptake among adults in Switzerland.

Methods

In this cross-sectional survey, we collected vaccination records from randomly selected adults 18-79 throughout Switzerland. Of 4,626 participants, data from individuals receiving at least 1 TBE vaccination (n=1875) were evaluated. We determined year and age of first vaccination and vaccine compliance, evaluating dose timeliness. Participants were considered “on time” if they received doses according to the recommended schedule ± a 15% tolerance period.

Results

45% of participants received their first TBE vaccination between 2006 and 2009. 25% were first vaccinated aged 50+ (mean age 37). More than 95% of individuals receiving the first dose also received the second; ∼85% of those receiving the second dose received the third. For individuals completing the primary series, 30% received 3 doses of Encepur, 58% received 3 doses of FSME-Immun, and 12% received a combination. According to conventional schedules, 88% and 79% of individuals received their second and third doses “on time”, respectively. 20% of individuals receiving Encepur received their third dose “too early”. Of individuals completing primary vaccination, 19% were overdue for a booster. Among the 31% of subjects receiving a booster, mean time to first booster was 7.1 years.

Conclusions

We estimate that a quarter of adults in Switzerland were first vaccinated for TBE aged 50+. Approximately 80% of participants receiving at least one vaccine dose completed the primary series. We further estimate that 66% of individuals completing the primary series adhered to an “ideal” TBE vaccination schedule.
Is the Association Between Smoking and Depression Mediated by Inflammation? A Mendelian Randomization Study
Authors: Galan D. , Perry B.I. , Warrier V. , Easton D. , Khandaker G.M. , Murray G.K.
Published: February 2021

Smoking, inflammation and depression commonly co-occur and may be mechanistically linked. However, key questions remain around the direction of association and the influence of residual confounding. We aimed to characterize the association between lifetime smoking and depression, as well as to assess the role that genetically-predicted C-reactive protein (CRP) level, an archetypal inflammatory marker, as a potential mediator for this association. We performed inverse variance weighted Mendelian randomization (MR) analyses using recently published summary-level GWAS data for lifetime smoking index, CRP levels, and depression. A subset of inflammatory-related genetic variants from the lifetime smoking GWAS were also used to assess the potential inflammatory causal pathways between smoking and depression. The analysis indicated significant reciprocal relationships between lifetime smoking and both depression (ORSmk-Dep = 2.01, 95% CI 1.71-2.37, p < 0.001; O RDep-Smk = 1.09, 95% CI 1.06-1.13, p < 0.001) and CRP levels (ORSmk-CRP = 1.40, 95% CI 1.21-1.55, p < 0.001; ORCRP-Smk = 1.03, 95% CI 1.02-1.05, p < 0.001). These significant and positive associations were also supported by the majority of the robust MR methods performed. The reciprocal relationships between CRP levels (using >500 genetic instruments for CRP) and depression were not significant (ORCRP-Dep = 1.01, 95% CI 0.99-1.04; ORDep-CRP = 1.03, 95% CI 0.99-1.07). We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to inflammation or when we adjusted the analysis by CRP-levels in multivariable analysis. Our study supports potential causal associations between lifetime smoking and depression, as well as between lifetime smoking and CRP levels, but not between CRP and depression. No evidence was found that CRP mediates the relationship between smoking and depression.
Distinct microRNA expression signatures of primary and secondary central nervous system lymphomas
Authors: Sebestyén Endre , Nagy Ákos , Marosvári Dóra , Rajnai Hajnalka , Kajtár Béla , Deák Beáta , Matolcsy András , Brandner Sebastian , Storhoff James , Chen Ning , Bagó Attila G. , Bödör Csaba , Reiniger Lilla
Published: February 2021

Central nervous system (CNS) lymphoma is a rare and aggressive non-Hodgkin lymphoma that might arise in the CNS (primary CNS lymphoma, PCNSL) or disseminates from a systemic lymphoma to the CNS (secondary CNS lymphoma, SCNSL). Dysregulated expression of microRNAs (miRNAs) is associated with various pathological processes and miRNA expression patterns may have diagnostic, prognostic and therapeutic implications. However, miRNA expression is understudied in CNS lymphomas. Here, we performed expression analysis of 798 miRNAs in 73 CNS lymphoma samples using the NanoString platform, followed by a detailed statistical analysis to identify potential novel biomarkers characterizing subgroups and to examine differences based on their primary and secondary nature, molecular subtype, mutational patterns and survival. We describe the general expression patterns of miRNAs across CNS lymphoma samples and identified 31 differentially expressed miRNAs between primary and secondary groups. Additionally, we identified 7 more miRNAs associated with a molecular subtype and 25 associated with mutation status. Using unsupervised clustering methods, we defined a small but distinct primary CNS lymphoma subgroup, with characteristically different expression patterns compared to the rest of the cases. Finally, we identified differentially regulated pathways in the above comparisons and assessed the utility of miRNA expression patterns in predicting survival. Our study identifies a novel CNS lymphoma subgroup defined by distinct miRNAs, proves the importance of specific miRNAs and pathways in their pathogenesis, and provides the basis for future research.
Acute Medical Unit Healthcare workers’ interaction in a developing country: Social Network Analysis
Authors: Belayachi Jihane , Benammi Sarah , Bennis Rhita Nechba , Madani Naoufel , Abouqal Redouane
Published: February 2021

INTRODUCTION

Social network analysis is used to increase the awareness of leaders about the power of networks, to further catalyze relationships and connections, and to strengthen the capacity of the network to act collectively. We focus on understanding and measuring the communication patterns in an acute medical unit team. We sought to use Social Network Analysis to describe the patterns of communications in teamwork of an acute medical unit.

METHODS

Network Analysis was conducted to examine network structure in 58 teamwork professional communication in an AMU. Team members reported the frequency (0 to 10+ times) of professional discussion with every other coworker during the last 48-hoursk, density, degree and betweenness centralization, degree and betweenness centrality; and homophily were calculated. P-value was obtained based on 1000 quadratic assignment procedure QAP permutations of the network. The network analysis was used to construct network maps using multidimentional scaling and generates a visual representation of networks through network diagrams.

RESULTS

there were 460 connections (density=28%). The whole network has a moderate degree centralization (37%) and lower betweenness centralization (8%). Three senior physicians, the head nurse, the physiotherapist, the medical secretary and the archive manager were most central in network. There was evidence regarding heterophily in a network indicated by high level of E-I index value 0.34 (P<0.01, by QAP).

CONCLUSION

SNA provided a description of patterns of communications in teamwork in an acute medical unit. We used SNA statistics to reveal variation in patterns of team communication and teammate interconnectedness by shift.
Sero-surveillance for IgG to SARS-CoV-2 at antenatal care clinics in two Kenyan referral hospitals
Authors: Lucinde R. , Mugo D. , Bottomley C. , Aziza R , Gitonga J. , Karanja H. , Nyagwange J. , Tuju J. , Wanjiku P. , Nzomo E. , Kamuri E. , Thuranira K. , Agunda S. , Nyutu G. , Etyang A. , Adetifa I. M. O. , Kagucia E. , Uyoga S. , Otiende M. , Otieno E. , Ndwiga L. , Agoti C. N. , Aman R. , Mwangangi M. , Amoth P. , Kasera K. , Nyaguara A. , Ng’ang’a W. , Ochola L. B. , Barasa E. , Bejon P. , Tsofa B. , Ochola-Oyier L. I. , Warimwe G. M. , Agweyu A. , Scott J. A. G. , Gallagher K. E.
Published: February 2021

The high proportion of SARS-CoV-2 infections that remain undetected presents a challenge to tracking the progress of the pandemic and implementing control measures in Kenya. We determined the prevalence of IgG to SARS-CoV-2 in residual blood samples from mothers attending antenatal care services at 2 referral hospitals in Kenya. We used a validated IgG ELISA for SARS-Cov-2 spike protein and adjusted the results for assay sensitivity and specificity. In Kenyatta National Hospital, Nairobi, seroprevalence in August 2020 was 49.9% (95% CI 42.7-58.0). In Kilifi County Hospital seroprevalence increased from 1.3% (95% CI 0.04-4.7) in September to 11.0% (95% CI 6.2-16.7) in November 2020. There has been substantial, unobserved transmission of SARS-CoV-2 in parts of Nairobi and Kilifi Counties.
Longitudinal Metabolomics of Human Plasma Reveals Robust Prognostic Markers of COVID-19 Disease Severity
Authors: Sindelar Miriam , Stancliffe Ethan , Schwaiger-Haber Michaela , Anbukumar Dhanalakshmi S. , Albrecht Randy A. , Liu Wen-Chun , Travis Kayla Adkins , García-Sastre Adolfo , Shriver Leah P. , Patti Gary J.
Published: February 2021

There is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that scarce medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we performed untargeted metabolomics profiling of 341 patients with plasma samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we then built a predictive model of disease severity. We determined that the levels of 25 metabolites measured at the time of hospital admission successfully predict future disease severity. Through analysis of longitudinal samples, we confirmed that these prognostic markers are directly related to disease progression and that their levels are restored to baseline upon disease recovery. Finally, we validated that these metabolites are also altered in a hamster model of COVID-19. Our results indicate that metabolic changes associated with COVID-19 severity can be effectively used to stratify patients and inform resource allocation during the pandemic.
C-bouton components on rat extensor digitorum longus motoneurons are resistant to chronic functional overload
Authors: Kissane Roger W.P. , Ghaffari-Rafi Arash , Tickle Peter G. , Chakrabarty Samit , Egginton Stuart , Brownstone Robert M. , Smith Calvin C.
Published: February 2021

Mammalian motor systems adapt to the demands of their environment. For example, muscle fibre types change in response to increased load or endurance demands. However, for adaptations to be effective, motoneurons must adapt such that their properties match those of the innervated muscle fibres. We used a rat model of chronic functional overload to assess adaptations to both motoneuron size and a key modulatory synapse responsible for amplification of motor output, C-boutons. Overload of Extensor Digitorum Longus (EDL) muscles was induced by removal of their synergists, Tibialis Anterior (TA) muscles. Following 21 days survival, EDL muscles showed an increase in fatigue resistance and a decrease in force output, indicating a shift to a slower phenotype. These changes were reflected by a decrease in motoneuron size. However, C-bouton complexes remained largely unaffected by overload. The C-boutons themselves, quantified by expression of vesicular acetylcholine transporter, were similar in size and density in the control and overload conditions. Expression of the post-synaptic voltage-gated potassium channel (KV2.1) was also unchanged. Small conductance calcium activated potassium channels (SK3) were expressed in most EDL motoneurons, despite this being an almost exclusively fast motor pool. Overload induced a decrease in the proportion of SK3+cells, however there was no change in density or size of clusters. We propose that reductions in motoneuron size may promote early recruitment of EDL motoneurons, but that C-bouton plasticity is not necessary to increase the force output required in response to muscle overload.
Two interconnected patterning loops are required for body axis and head organizer formation inHydra
Authors: Mercker Moritz , Tursch Anja , Veerman Frits , Kazarnikov Alexey , Höger Stefanie , Lengfeld Tobias , Özbek Suat , Holstein Thomas W , Marciniak-Czochra Anna
Published: February 2021

The formation of body axes and apical termini is crucial for animal development. InHydra, nuclearβ-catenin and Wnt3 play key roles and were previously thought to be part of a single mechanism for axis and head formation. This study challenges this view by combining mathematical modeling with experimental data. We show thatβ-catenin and Wnt3 patterning in Hydra operate at two different scales, requiring distinct inhibitory mechanisms.β-catenin, possibly interacting with other Wnts, co-ordinates axis formation, whereas Wnt3 is involved in small-scale head patterning. A double-loop reaction-diffusion model was developed, demonstrating the ability to describe patterns with divergent shapes, which single-loop models could not achieve. The previously proposed threshold mechanism for Wnt3 expression based onβ-catenin prepatterns could not explain the data. Our results suggest a more complex patterning mechanism in other animals, where axis and head formation may not be controlled by a single process.
Optical analysis of the action range of glutamate in the neuropil
Authors: Matthews E.A. , Sun W. , McMahon S.M. , Doengi M. , Halka L. , Anders S. , Müller J.A. , Steinlein P. , Vana N. , van Dyk G. , Pitsch J. , Becker A.J. , Pfeifer A. , Kavalali E.T. , Lamprecht A. , Henneberger C. , Stein V. , Schoch S. , Dietrich D.
Published: February 2021

The wiring scheme of neurons is key to the function of the brain. Neurons are structurally wired by synapses and it is a long-held view that most synapses in the CNS are sufficiently isolated to avoid cross-talk to AMPA receptors of neighboring synapses. Here we report in hippocampal brain slices that quantal glutamate release activated optical reporter proteins >1.5 µm distant to the releasing synapse. 2P-glutamate uncaging was used to quantitatively probe glutamate spread in the neuropil. Releasing ∼35000 molecules of glutamate (∼5 vesicles) at a distance of 500 nm to a spine generated an uncaging EPSC reaching ∼30% of the quantal amplitude at synaptic AMPA-Rs. The same stimulus activated ∼70% of the quantal amplitude at NMDA-Rs and still generated clear current and calcium responses when applied at >= 2 µm remote to the spine. Extracellular spread of glutamate on the sub-micrometer scale appeared cooperative and caused supra-additive activation of AMPA-Rs in a spine. These observations are not predicted by previously used models of glutamate diffusion in the neuropil. An extracellular glutamate scavenger system weakly reduced field potential responses but not the quantal amplitude, indicating that a cross-talk component regularly contributes to synaptic transmission. Our data suggest that slight synaptic crosstalk responses at AMPA receptors of ∼2-4 adjacent synapses may be common (>70 synapses for NMDA receptors). Such broadcasting of synaptic signals to very local neighborhoods could stabilize network learning performance and allow for integration of synaptic activity within the extracellular space.