bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic training program for nursing home staff based on the concept of combination of medicine and care
Authors: Wang Lin , Chen Hong , Yang Liu , Qian Chunhua , Sun Dongmei , Sun Yan
Published: June 2020

It is important to improve the training for nursing home staff in order to achieve better quality of life for the elderly.

This study aimed to develop a systematic training program for nursing home staff based on the concept of combination of medicine and care.

Thirty-four nursing staff from 2 representative nursing homes in Qiqihar City were selected as study subjects and divided into experimental and control groups. The subjects in both groups received routine training following “National Occupational Standards of Elderly Nursing Staff”. In addition, the subjects in experimental groups received systematic training at three levels based on the concept of combination of medicine and care for 4 months.

After the training, the competence scores of nursing staff in experimental group increased significantly compared to control group, the living quality of the elderly in nursing homes cared by nursing staff in experimental group was significantly improved, and the satisfaction of the elderly to nursing staff in experimental group improved significantly, compared to control group (P < .05).

We develop systematic training program for nursing home staff based on the concept of combination of medicine and care, which can improve nursing care for the elderly in nursing home.
Efficacy of albumin–bilirubin score to predict hepatic encephalopathy in patients underwent transjugular intrahepatic portosystemic shunt
Authors: Lin Xinran , Gao Feng , Wu Xixi , Cai Weimin , Chen Xiaofu , Huang Zhiming
Published: June 2020

Background and aims

The occurrence of hepatic encephalopathy is one of the main factors limiting the development and application of transjugular intrahepatic portosystemic shunt (TIPS). Our study aimed to verify the efficacy of the albumin–bilirubin score, an objective and simple scoring system, to predict post-TIPS hepatic encephalopathy.

Methods

From February 2014 to July 2019, a total of 224 patients who underwent TIPS procedure were entered into the study. All patients were followed up after TIPS placement. Relevant clinical data within 24 h after admission were collected to compare the differences between patients with and without hepatic encephalopathy after TIPS placement.

Results

A total of 82 (36.6%) patients developed post-TIPS hepatic encephalopathy. Age and albumin–bilirubin score was found to be independent risk factors for post-TIPS hepatic encephalopathy. The albumin–bilirubin score shows a good ability to predict the occurrence of hepatic encephalopathy within 1 year after TIPS. The area under the receiver operating characteristic curve is 0.74 (95% confidence interval: 0.673–0.806). In addition, in order to improve its feasibility, we regrouped the albumin–bilirubin score into three levels (albumin–bilirubin≤ –1.95, low risk; 1.95  –1.45, high risk).

Conclusion

The albumin–bilirubin score has a good predictive value for the possibility of post-TIPS hepatic encephalopathy, which is better than the model for end-stage liver disease and Child-Pugh score.
Risk Factors Associated With Bronchiolitis in Puerto Rican Children
Authors: Rivera-Sepúlveda Andrea , García-Rivera Enid , Castro Mario , Soto Fernando
Published: June 2020

Objective

The objective of this study was to identify frequency, severity, and risk factors associated with bronchiolitis in Puerto Rican children.

Methods

A cross-sectional was study performed at 4 emergency departments of Puerto Rico's metropolitan area, between June 2014 and May 2015. We included children younger than 24 months, with a clinical diagnosis of bronchiolitis, who were born and living in Puerto Rico at the time of recruitment. A physician-administered questionnaire inquiring about the patient's medical, family, and social history and a bronchiolitis severity assessment were performed. Daily weather conditions were monitored, and aeroallergens were collected with an air sample and precision weather station within the metropolitan area to evaluate environmental factors.

Results

We included 600 patients for 12 months. More than 50% of the recruited patients had a previous episode of bronchiolitis, of which 40% had been hospitalized. Older age (odds ratio [OR], 18.3; 95% confidence interval [CI], 9.2–36.5), male sex (OR, 1.6; 95% CI, 1.1–2.4), history of asthma (OR, 8.9; 95% CI, 3.6–22), allergic rhinitis (OR, 3.6; 95% CI, 1.8–7.4), and smoke exposure by a caretaker (OR, 2.3; 95% CI, 1.2–4.4) were predictors of bronchiolitis episodes. Bronchiolitis episodes were associated with higher severity score (P = 0.040), increased number of atopic factors (P < 0.001), and higher number of hospitalizations (P < 0.001).

Conclusions

This study identifies Puerto Rican children who may present a severe clinical course of disease without traditional risk factors. Atopy-related factors are associated with frequency and severity of bronchiolitis. Puerto Rican children present risk factors related to atopy earlier in life, some of which may be modified to prevent the subsequent development of asthma.
Bridging the Gap
Authors: Martin Philip Aidan , Loughins Lyndsay , Weatherup Nicola , Mullen Stephen
Published: June 2020

Introduction

Adolescents are attending emergency departments (EDs) in increasing numbers, accounting for 21% attendances in the United Kingdom. A recent report by the Northern Ireland Commissioner for Children and Young People highlighted deficiencies in the support offered by EDs to adolescents.

Aim

The aim of this study was to develop a high-fidelity simulation-based course focused on managing common adolescent presentations to the ED.

Methodology

A 1-day mixed-modality course comprising of simulations, lectures, and skill stations, mapped to the pediatric and emergency medicine curriculum, was designed. The faculty developed and delivered 8 high-fidelity simulations. Precourse and immediate postcourse questionnaires were used to assess confidence levels and gain qualitative data. Delayed feedback was collected at 3 months.

Results

There were 36 participants; 86% (n = 31) completed the precourse feedback, 96% (n = 34) completed the postcourse feedback, and 47% (n = 17) completed the delayed feedback. There was a statistically significant increase in self-reported confidence across all domains with a median increase of 21.25% immediately, sustained at 20% on delayed 3-month feedback. Qualitative feedback noted a change in practice, “I used (the knowledge) regularly while working in children's A + E.”

Conclusions

This was a feasible, high-fidelity simulation-based study day covering the key components of adolescent medicine. The sustained increase in confidence at 3 months and the positive qualitative and quantitative feedback are supportive of the use of simulation to improve adolescent emergency care.
Interobserver Agreement of Inferior Vena Cava Ultrasound Collapse Duration and Correlated Outcomes in Children With Dehydration
Authors: Zhou Amy Z. , Green Robert S. , Haines Elizabeth J. , Vazquez Michelle N. , Tay Ee T. , Tsung James W.
Published: June 2020

Objective

Dehydration is a common concern in children presenting to pediatric emergency departments and other acute care settings. Ultrasound (US) of the inferior vena cava (IVC) may be a fast, noninvasive tool to gauge volume status, but its utility is unclear. Our objectives were to determine the interobserver agreement of IVC collapse and collapse duration, then correlate IVC collapse with the outcome of intravenous (IV) versus oral (PO) rehydration.

Methods

We conducted a prospective study by enrolling patients 0 to 21 years old with emesis requiring ondansetron or diarrhea requiring IV hydration. Clinical operators interpreted US examinations in real time to determine whether the IVC was collapsed. Two blinded reviewers interpreted the US videos to determine IVC collapse and collapse duration. Cohen's kappa(κ) was calculated for reviewer-reviewer and reviewer-operator agreement. Primary outcomes were PO versus IV rehydration, and admitted versus discharged.

Results

One hundred twelve patients were enrolled, and 102 had complete data for analysis. The mean age was 7.2 years with 51% female. Twenty-nine patients received IV hydration. The reviewer-operator agreement for IVC collapse was κ = 0.57 (95% confidence interval [CI], 0.38–0.75) and interreviewer agreement was κ = 0.93 (95% CI, 0.83–1.0). The interreviewer agreement for collapse duration was κ = 0.66 (95% CI, 0.51–0.82). All patients with noncollapsed IVCs tolerated PO hydration. The likelihood of receiving IV hydration was correlated with the duration of IVC collapse (P = 0.034).

Conclusions

Based on a novel dynamic measure of IVC collapse duration, children with increasing duration of IVC collapse correlated positively with the need for IV rehydration. Noncollapsing IVCs on US were associated with successful PO rehydration without need for IV fluids or emergency department revisits.
Immune and Cell Therapy in Non-Hodgkin Lymphoma
Authors: Merryman Reid W. , Houot Roch , Armand Philippe , Jacobson Caron
Published: June 2020

The promise of immunotherapy has shone brightly for decades in hematologic malignancies and specifically in non-Hodgkin lymphoma. The last decade has witnessed the emergence of completely novel forms of immunotherapy, including immune checkpoint blockade, bispecific antibodies, and chimeric antigen receptor T cells. These treatments have shown phenomenal, and in some cases possibly curative, successes in various relapsed/refractory lymphomas. This review summarizes the most notable successes and promising findings as well as some of the attendant failures. These treatments will doubtlessly transform the treatment paradigms across many lymphoma subtypes. Yet, only if we can better understand their mechanisms of action, toxicity, and resistance will be able to maximize their therapeutic benefit.
Role of Microenvironment in Non-Hodgkin Lymphoma
Authors: Khurana Arushi , Ansell Stephen M.
Published: June 2020

Lymphoma microenvironment is a dynamic and well-orchestrated network of various immune and stromal cells that is indispensable for tumor cell survival, growth, migration, immune escape, and drug resistance. Recent progress has enhanced our knowledge of the pivotal role of microenvironment in lymphomagenesis. Understanding the characteristics, functions, and contributions of various components of the tumor niche, along with its bidirectional interactions with tumor cells, is paramount. It offers the potential to identify new therapeutic targets with the ability to restore antitumor immune surveillance and eliminate the protumoral factors contributed by the tumor niche.
Lymphoma Classification
Authors: de Leval Laurence , Jaffe Elaine S.
Published: June 2020

Twenty-five years after the Revised European American Classification of Lymphoid Neoplasms classification was published, its principle of an integrative approach to disease definition based on several parameters still prevails and has been adopted and expanded in the following World Health Organization classifications of tumors of the hematopoietic organs. The latest World Health Organization classification revised in 2017 comprises more than 80 entities of mature lymphoid neoplasms (B-cell, T-cell, and Hodgkin lymphomas), which are defined according to their morphology, immunophenotype, genetic lesions and molecular profiles, clinical features, and cellular derivation. The classification also recognizes both incipient and indolent lymphoid neoplasms with a low potential of progression. In this review, we highlight some of the new data and recent modifications introduced in the 2017 classification.
Use of the Adductor Magnus Muscle Free Flap for Lower-Extremity Soft Tissue Coverage
Authors: Melissinos Emmanuel G. , Maiorino Eric J. , Marques Erik S.
Published: June 2020

Background

The gracilis muscle free flap has proven to be a dependable tool for the reconstructive microsurgeon for coverage of small- to medium-sized lower-extremity soft tissue defects because of its reliable anatomy, ease of elevation, and minimal donor site morbidity. We describe our experience with the adductor magnus muscle free flap which we have utilized in cases when confronted with the rare situation in which the dominant vascular pedicle to the gracilis muscle is insufficient or absent.

Methods

We conducted a retrospective chart review of a single surgeon's experience (EG Melissinos) over an 18-year period of all patients that underwent adductor magnus muscle free flap coverage for lower-extremity soft tissue injuries.

Results

Twenty-four adductor magnus free flaps in 24 patients were performed over an 18-year period (2000–2018). All of the adductor magnus muscle free flaps were performed with the initial intention of gracilis muscle harvest for lower-extremity soft tissue coverage. The most common wound etiology was motor vehicle collisions (8 patients, 33%). All of the adductor magnus free flaps were used for coverage of lower-extremity wounds in the following anatomic locations: distal third (10 patients, 41.7%), ankle (11 patients, 45.8%) and foot (3 patients, 12.5%). All flaps were successful. There were minimal donor site complications. Limb salvage rate was 100%.

Conclusions

Use of the adductor magnus muscle free flap is a reasonable alternative to the gracilis muscle in cases when unfavorable gracilis vascular anatomy is encountered intraoperatively. It can be easily and safely harvested within the same donor incision and permits reliable coverage of small- to medium-sized lower-extremity soft tissue defects while avoiding the morbidity of a secondary donor site.
Vaginal Sacrospinous Ligament Fixation Using Tissue Anchoring System Versus a Traditional Technique for Women With Apical Vaginal Prolapse: A Randomized Controlled Trial
Authors: Castro Rodrigo Aquino , Bortolini Maria Augusta Tezelli , Pascom Ana Lívia Garcia , Ledesma Marta , Sardi Juan José Luis , Monteiro Marilene Vale de Castro , Junqueira Sebastián Perez , Fuentes Edna Cortes
Published: June 2020

Objective

The aim of the study was to compare the efficacy and safety of the tissue anchoring system (TAS) kit versus the traditional technique for sacrospinous ligament fixation (SSLF) to treat apical vaginal wall prolapse.

Methods

A prospective randomized controlled multicenter study of noninferiority involving women with apical prolapse (C-point≥+1). Primary outcome is surgical success as C-point≤−4 at the 1-year follow-up. Secondary outcomes are success according to the composite criteria as C-point≤−4, Ba-point ≤0, and Bp-point ≤0; POP-Q measures of the vaginal compartments; intraoperative findings, complications; reoperation rate; hospital stay; and quality of life and sexual functioning (PISQ-12). It was estimated that 50 individuals per group would yield an 80% power for a noninferiority margin of 15%.

Results

Ninety-nine women were randomized: TAS (n = 55) and traditional SSLF (n = 44). The groups’ preoperative data were similar. Drop-out rate was 11% for 12-month follow-up. Success rates were 90% for TAS and 80% for traditional SSLF (P = 0.0006; absolute difference, 9.8%; 90% confidence interval, −5.2 to 24.8) with the sensivity analyses per-protocol considering only the subjects that completed the 12-month follow-up and 80% versus 73%, respectively (P = 0.0048; absolute difference, 7.3%; 90% confidence interval, −9.6 to 24.2) by sensivity analyses considering the total number of participants randomized and treated with drop-out cases as failure. We detected shorter intraoperative time to dissect and reach the SSL, shorter length of hospitalization, lower rates of urinary tract infection, and lower pain scores in the first 30 days postoperative in the TAS compared with the traditional SSLF groups (P < 0.05). There was an improvement in women’s quality of life that did not differ between groups.

Conclusions

The modified technique of SSLF using the TAS kit is noninferior to the traditional technique for the treatment of apical compartment in 12-month follow-up.
5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control
Authors: Yousefzadeh Farzaneh , Sahebolzamani Erfan , Sadri Arash , Mortezaei Amirhosein , Aqamolaei Ali , Mortazavi Seyyed Hosein , Shalbafan Mohammd Reza , Ghaffari Salomeh , Alikhani Rosa , Mousavi Seiedeh Bentolhoda , Naderi Sina , Shamabadi Ahmad , Jalilevand Shakiba , Akhondzadeh Shahin
Published: June 2020

On the basis of numerous previous studies, the serotonergic system plays a role in the pathogenesis of obsessive-compulsive disorder (OCD) and effective agents in this pathway, such as 5-hydroxytryptophan, can potentially contribute to treatment of patients with this disorder. Evaluating the efficacy of 5-hydroxytryptophan in treating OCD was the aim of the present randomized, double-blind, placebo-controlled 12-week trial. In a 12-week, randomized double-blind study, 60 patients with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of moderate to severe OCD and a Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score of >21 were randomly assigned to receive either fluoxetine plus placebo or fluoxetine plus 5-hydroxytryptophan (100 mg twice daily). All patients, regardless of their treatment group, received fluoxetine at 20 mg/day for the initial 4 weeks of the study followed by 60 mg/day of fluoxetine for the rest of the trial course. Symptoms were assessed using the Y-BOCS at baseline and weeks 4, 8 and 12. General linear model repeated measure showed significant effects for time × treatment interaction on total Y-BOCS (F = 12.07, df = 2.29, P-value <0.001), obsession (F = 8.25, df = 1.91, P-value = 0.001) and compulsion subscale scores (F = 6.64, df = 2.01, P-value = 0.002). 5-Hydroxytryptophan augmentation therapy demonstrated higher partial and complete treatment response rate (P = 0.032 and P = 0.001, respectively) according to the Y-BOCS total scores. The results of this study confirm that 5-hydroxytryptophan may be effective as an augmentative agent in treatment of moderate-to-severe OCD.
Biostratinomy of the Ediacara Member (Rawnsley Quartzite, South Australia): implications for depositional environments, ecology and biology of Ediacara organisms
Authors: Droser Mary L. , Tarhan Lidya G. , Evans Scott D. , Surprenant Rachel L. , Gehling James G.
Published: June 2020

The Precambrian Ediacara Biota—Earth's earliest fossil record of communities of macroscopic, multicellular organisms—provides critical insights into the emergence of complex life on our planet. Excavation and reconstruction of nearly 300 m
2
of fossiliferous bedding planes in the Ediacara Member of the Rawnsley Quartzite, at the National Heritage Ediacara fossil site Nilpena in South Australia, have permitted detailed study of the sedimentology, taphonomy and palaeoecology of Ediacara fossil assemblages. Characterization of Ediacara macrofossils and textured organic surfaces at the scale of facies, bedding planes and individual specimens has yielded unprecedented insight into the manner in which the palaeoenvironmental settings inhabited by Ediacara communities—particularly hydrodynamic conditions—influenced the aut- and synecology of Ediacara organisms, as well as the morphology and assemblage composition of Ediacara fossils. Here, we describe the manner in which environmental processes mediated the development of taphofacies hosting Ediacara fossil assemblages. Using two of the most common Ediacara Member fossils,
Arborea
and
Dickinsonia
, as examples, we delineate criteria that can be used to distinguish between ecological, environmental and biostratinomic signals and reconstruct how interactions between these processes have distinctively shaped the Ediacara fossil record.
Weathering, alteration and reconstructing Earth's oxygenation
Authors: Planavsky Noah J. , Robbins Leslie J. , Kamber Balz S. , Schoenberg Ronny
Published: June 2020

Deciphering the role—if any—that free oxygen levels played in controlling the timing and tempo of the radiation of complex life is one of the most fundamental questions in Earth and life sciences. Accurately reconstructing Earth's redox history is an essential part of tackling this question. Over the past few decades, there has been a proliferation of research employing geochemical redox proxies in an effort to tell the story of Earth's oxygenation. However, many of these studies, even those considering the same geochemical proxy systems, have led to conflicting interpretations of the timing and intensity of oxygenation events. There are two potential explanations for conflicting redox reconstructions: (i) that free oxygen levels were incredibly dynamic in both time and space or (ii) that collectively, as a community—including the authors of this article—we have frequently studied rocks affected by secondary weathering and alteration (particularly secondary oxidation) while neglecting to address the impact of this alteration on the generated data. There are now multiple case studies that have documented previously overlooked secondary alteration, resolving some of the conflicting constrains regarding redox evolution. Here, an analysis of a large shale geochemistry database reveals significant differences in cerium (Ce) anomalies, a common palaeoredox proxy, between outcrop and drill core samples. This inconsistency provides support for the idea that geochemical data from altered samples are frequently published in the peer-reviewed literature. As individuals and a geochemical community, most of us have been slow to appreciate how pervasive the problem is but there are examples of other communities that have faced and met the challenges raised by such quality control crises. Further evidence of the high potential for alteration of deep-time geochemical samples, and recognition of the manner in which this may lead to spurious results and palaeoenvironmental interpretations, indicate that sample archiving, in publicly accessible collections needs to become a prerequisite for publication of new palaeoredox data. Finally, the geochemical community need to think about ways to implement additional quality control measures to increase the fidelity of palaeoredox proxy work.
On the use of models in understanding the rise of complex life
Authors: Lenton Timothy M.
Published: June 2020

Recently, several seemingly irreconcilably different models have been proposed for relationships between Earth system processes and the rise of complex life. These models provide very different scenarios of Proterozoic atmospheric oxygen and ocean nutrient levels, whether they constrained complex life, and of how the rise of complex life affected biogeochemical conditions. For non-modellers, it can be hard to evaluate which—if any—of the models and their results have more credence—hence this article. I briefly review relevant hypotheses, how models are being used to incarnate and sometimes test those hypotheses, and key principles of biogeochemical cycling models should embody. Then I critically review the use of biogeochemical models in: inferring key variables from proxies; reconstructing ancient biogeochemical cycling; and examining how complex life affected biogeochemical cycling. Problems are found in published model results purporting to demonstrate long-term stable states of very low Proterozoic atmospheric
p
O
2
and ocean P levels. I explain what they stem from and highlight key empirical uncertainties that need to be resolved. Then I suggest how models and data can be better combined to advance our scientific understanding of the relationship between Earth system processes and the rise of complex life.
Pandemic planning: plotting a course through the coronawars
Authors: Inglis Timothy J. J.
Published: June 2020

The biological motor behind the current coronavirus pandemic has placed microbiology on a global stage, and given its practitioners a role among the architects of recovery. Planning for a return to normality or the new normal is a complex, multi-agency task for which healthcare scientists may not be prepared. This paper introduces a widely used military planning framework known as the Joint Military Appreciation Process, and outlines how it can be applied to deal with the next phase of the COVID-19 pandemic. Recognition of SARS-CoV-2's critical attributes, targetable vulnerabilities, and its most likely and most dangerous effects is a necessary precursor to scoping, framing and mission analysis. From this flows course of action development, analysis, concept of operations development, and an eventual decision to act on the plan. The same planning technique is applicable to the larger scale task of setting a microbiology-centric plan in the broader context of social and economic recovery.
The disordered regions of SETD2 govern H3K36me3 deposition by regulating its proteasome-mediated decay
Authors: Bhattacharya Saikat , Zhang Ning , Li Hua , Workman Jerry L.
Published: June 2020

SETD2 is the sole methyltransferase that tri-methylates histone H3 at lysine 36 in mammals. It has an extended N-terminal region which is absent in its yeast homolog Set2. The function of this poorly characterized region in regulating SETD2 stability has been reported. However, how this region regulates SETD2 half-life and the consequences of the cellular accumulation of SETD2 is unclear. Here we show that the SETD2 N-terminal region contains disordered regions and is targeted for degradation by the proteasome. The marked increase in global H3K36me3 that occurs on the removal of the N-terminal segment results in a non-canonical distribution including reduced enrichment over gene bodies and exons. An increased SETD2 abundance leads to widespread changes in transcription and alternative splicing. Thus, the regulation of SETD2 levels through intrinsically disordered region-facilitated proteolysis is important to maintain the fidelity of transcription and splicing related processes.
Harmonized Z-scores calculated from the large scale normal MRI database to evaluate brain atrophy for neurodegenerative disorder
Authors: Maikusa Norihide
Published: June 2020

Alzheimer’s disease (AD), the most common type of dementia in elderly individuals, slowly and progressively diminishes cognitive function. Mild cognitive impairment is also a significant risk factor to the onset of AD. Magnetic resonance imaging (MRI) images have become widely used to detection and understand the natural progression not only AD but also neurodegenerative disorders. For this purpose, construct a reliable cognitive normal database is important. However, difference in magnetic field strength, sex and age between normal database and evaluation data-set can be affect the accuracy of detection and evaluation of AD and other neurodegenerative disorders.

To solve this problem, we suggest a harmonized Z-score considering differences filed strength, sex and age derived from large cognitive normal subjects dataset ((1235 subjects)) including 1.5 T and 3T T1 brain MRI. And we evaluate our harmonized Z-score of discriminative power of AD, and classification accuracy between stable MCI and progressive MCI.

The harmonized Z-score of hippocampus achieved high accuracy (AUC=0.96) for detection AD and moderate accuracy (AUC=0.70) for classification stable MCI and progressive MCI. Theses results shows that our method not only can detect AD with high accuracy and high generalization capability, but also can be valid to classify stable MCI and progressive MCI.
Endochondral bone in an Early Devonian ‘placoderm’ from Mongolia
Authors: Brazeau Martin D. , Giles Sam , Dearden Richard P. , Jerve Anna , Ariunchimeg Y.A. , Zorig E. , Sansom Robert , Guillerme Thomas , Castiello Marco
Published: June 2020

Endochondral bone is the main internal skeletal tissue of nearly all osteichthyans—the group comprising more than 60,000 living species of bony fishes and tetrapods. Chondrichthyans (sharks and their kin) are the living sister group of osteichthyans and have cartilaginous endoskeletons, long considered the ancestral condition for all jawed vertebrates (gnathostomes). The absence of bone in modern jawless fishes and the absence of endochondral ossification in early fossil gnathostomes appears to lend support to this conclusion. Here we report the discovery of extensive endochondral bone inMinjinia turgenensis, a new genus and species of ‘placoderm’-like fish from the Early Devonian (Pragian) of western Mongolia described using x-ray computed microtomography (XR-µCT). The fossil consists of a partial skull roof and braincase with anatomical details providing strong evidence of placement in the gnathostome stem group. However, its endochondral space is filled with an extensive network of fine trabeculae resembling the endochondral bone of osteichthyans. Phylogenetic analyses place this new taxon as a proximate sister group of the gnathostome crown. These results provide direct support for theories of generalised bone loss in chondrichthyans. Furthermore, they revive theories of a phylogenetically deeper origin of endochondral bone and its absence in chondrichthyans as a secondary condition.
Gastrointestinal parasite community in the critically endangered West African lion
Authors: Kruszka Sofia , Harris Nyeema C.
Published: June 2020

Large carnivores of Africa, such as lions (Panthera leo), suffer from prey depletion and habitat fragmentation, that possibly impact the composition of the gastrointestinal parasite community. West African lions are particularly important, as this population is critically endangered and yet little is known of their gastrointestinal parasite community, which can reflect the health and resilience of the host population. From fecal samples collected in the W-Arly-Pendjari (WAP) transboundary protected area complex in Burkina Faso and Niger, we identified 309 oocysts of at least five different species using fecal flotation and sedimentation tests. We also compared these gastrointestinal parasites to other results from surveys of lions from Southern and East African regions and found similar taxa to previous surveys, but lower species richness across West African samples.
APhelipanche ramosaKAI2 Protein Perceives enzymatically Strigolactones and Isothiocyanates
Authors: de Saint Germain Alexandre , Jacobs Anse , Brun Guillaume , Pouvreau Jean-Bernard , Braem Lukas , Cornu David , Clavé Guillaume , Baudu Emmanuelle , Steinmetz Vincent , Servajean Vincent , Wicke Susann , Gevaert Kris , Simier Philippe , Goormachtig Sofie , Delavault Philippe , Boyer François-Didier
Published: June 2020

Phelipanche ramosais an obligate root-parasitic weed threatening major crops in central Europe. For its germination, it has to perceive various structurally diverging host-exuded signals, including isothiocyanates (ITCs) and strigolactones (SLs). However, the receptors involved are still uncharacterized. Here, we identified five putative SL receptors inP. ramosa, of which PrKAI2d3 is involved in seed germination stimulation. We established the high plasticity of PrKAI2d3, allowing interaction with different chemicals, including ITCs. The SL perception mechanism of PrKAI2d3 is similar to that of endogenous SLs in non-parasitic plants. We provide evidence that the PrKAI2d3 enzymatic activity confers hypersensitivity to SLs. Additionally, we demonstrated that methylbutenolide-OH binds PrKAI2d3 and stimulatesP. ramosagermination with a bioactivity comparable to that of ITCs. This study highlights thatP. ramosahas extended its signal perception system during evolution, a fact to be considered in the development of specific and efficient biocontrol methods.
SAMHD1mutations in mantle cell lymphoma are recurrent and conferin vitroresistance to nucleoside analogues
Authors: Bühler Marco M , Lu Junyan , Scheinost Sebastian , Nadeu Ferran , Roos-Weil Damien , Hensel Manfred , Thavayogarajah Tharshika , Moch Holger , Manz Markus G , Haralambieva Eugenia , Maggio Ewerton Marques , Beà Sílvia , Giné Eva , Campo Elías , Bernard Olivier A. , Huber Wolfgang , Zenz Thorsten
Published: June 2020

The genomic landscape of mantle cell lymphoma (MCL) includes frequent alterations ofTP53,ATM,CCND1andKMT2D. Thus far, the mutational landscape provides little information for treatment stratification. We characterized a cohort of MCL by targeted next generation sequencing and discoveredSAMHD1as a novel recurrently mutated gene (8.5% of investigated cases, 4/47 samples). Furthermore, we provide evidence of in vitro resistance ofSAMHD1mutated patient-derived MCL cells to cytarabine and fludarabine.
Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors
Authors: van Sorge Nina M. , Bonsor Daniel A. , Deng Liwen , Lindahl Erik , Schmitt Verena , Lyndin Mykola , Schmidt Alexej , Nilsson Olof R. , Brizuela Jaime , Boero Elena , Sundberg Eric J. , van Strijp Jos A.G. , Doran Kelly S. , Singer Bernhard B. , Lindahl Gunnar , McCarthy Alex J.
Published: June 2020

Streptococcus agalactiae, also known as group BStreptococcus(GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria at mucosal surfaces. Though several GBS adhesins have been identified, the host receptor targets of these adhesins remain unknown. We report here that surface-expressed β protein from GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that the IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessments revealed that this newly identified IgI3 fold is not exclusively present in GBS. Instead, the IgI3 fold is predicted to be present in adhesins from other clinically important human pathogens. We confirmed the interaction between CEACAM1 and the predicted IgI3-containing adhesin in two different streptococcal pathogens. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.
RIL-StEp: epistasis analysis of recombinant inbred lines (RILs) reveals candidate interacting genes that control rice seed hull color
Authors: Sakai Toshiyuki , Abe Akira , Shimizu Motoki , Terauchi Ryohei
Published: June 2020

Studying epistatic gene interactions is important in understanding genetic architecture of complex traits in organisms. However, due to an enormous number of gene combinations to be analyzed, detection of epistatic gene-gene interactions has been computationally demanding. Here, we show a simple approach RIL-StEp, specialized to Recombinant Inbred Lines (RILs), to study epistasis using single nucleotide polymorphisms (SNPs) information of the genome. We applied the method to reveal epistasis affecting rice seed hull color phenotype, and successfully identified gene pairs that presumably control seed hull color. This method has a potential to enhancing our understanding of genetic architecture of various traits.
Phenotypic melanoma heterogeneity is regulated through cell-matrix interaction-dependent changes in tumor microarchitecture
Authors: Spoerri Loredana , Tonnessen-Murray Crystal A. , Gunasingh Gency , Hill David S. , Beaumont Kimberley A. , Jurek Russell J. , Chauhan Jagat , Vanwalleghem Gilles C. , Fane Mitchell E. , Daignault-Mill Sheena M. , Matigian Nicholas , Boyle Glen M. , Scott Ethan K. , Smith Aaron G. , Stehbens Samantha J. , Schaider Helmut , Gabrielli Brian , Weninger Wolfgang , Goding Colin R. , Haass Nikolas K.
Published: June 2020

Phenotypic heterogeneity of cancer cells plays a critical role in shaping treatment response. This type of heterogeneity is organized spatially with specific phenotypes, such as sharply demarcated clusters of proliferating and cell cycle-arrested cells, predominating within discrete domains within a tumor. What determines the occurrence of specific tumor cell phenotypes in distinct microdomains of solid cancers is poorly understood. Here, we show that in melanoma spatial organization of phenotypic heterogeneity is dictated by the expression and activity of MITF. We reveal that this lineage survival oncogene controls ECM composition and organization, and ROCK-driven mechanotransduction through focal adhesion maturation and actin cytoskeleton functionality. In turn, altered tumor microarchitecture and structural integrity impact tumor solid stress which then mediates phenotypic heterogeneity through p27Kip1. Rho-ROCK-myosin signaling is necessary to transmit the effect of the reciprocal cell-ECM regulation into phenotypic heterogeneity. Our findings place cell-ECM crosstalk as a central driver of phenotypic tumor heterogeneity.

Significance

Phenotypic heterogeneity is a major culprit of cancer therapy failure. We demonstrate that phenotypic heterogeneity is controlled through tumor cell-ECM crosstalk resulting in altered tumor microarchitecture, mechanotransduction and Rho-ROCK-myosin signaling. Melanoma shares these physical properties with any solid cancer underscoring the importance of our findings for therapeutically targeting this phenomenon.
Neuronal dysfunctions and cognitive deficits in a multi-hit rat model following cumulative effects of early life stressors
Authors: Sarkar Tiyasha , Patro Nisha , Patro Ishan Kumar
Published: June 2020

Perinatal protein malnourishment is a leading cause for mental and physical retardation in children with poor socioeconomic conditions. Such malnourished children are vulnerable to additional stressors, that may synergistically act to cause neurological disorders at adulthood. In this study, the above mentioned condition is mimicked via a multi-hit rat model in which pups born to protein malnourished mothers (LP) were co-injected with polyinosinic:polycytidylic acid (Poly I:C; viral mimetic) at Postnatal day (PND) 3 and lipopolysaccharide (LPS; bacterial mimetic) at PND 9. Individual exposure of Poly I:C and LPS was also given to LP pups to correlate chronicity of stress. Similar treatments were also given to control pups. Hippocampal cellular apoptosis, β III tubulin catastrophe, altered neuronal profiling and spatial memory impairments were assessed at PND 180, using specific immunohistochemical markers (active caspase 3, β III tubulin, doublecortin), Golgi studies and cognitive mazes (Morris Water Maze and T maze). Increase in cellular apoptosis, loss of dendritic arborization and spatial memory impairments were higher in multi-hit group, than the single-hit groups. Such impairments observed due to multi-hit stress, mimic conditions similar to many neurological disorders and hence it is hypothesized that later life neurological disorders might be an outcome of multiple early life hits.

Summary Statement

This study is first of its kind which practically studies the combined effects of major early life stressors like protein malnourishment, viral and bacterial infections on the nervous system.
One-Step Rapid Quantification of SARS-CoV-2 Virus Particles via Low-Cost Nanoplasmonic Sensors in Generic Microplate Reader and Point-of-Care Device
Authors: Huang Liping , Ding Longfei , Zhou Jun , Chen Shuiliang , Chen Fang , Zhao Chen , Zhang Yiyi , Xu Jianqing , Hu Wenjun , Ji Jiansong , Xu Hao , Liu Gang L.
Published: June 2020

The spread of SARS-CoV-2 virus in the ongoing global pandemics has led to infections of millions of people and losses of many lives. The rapid, accurate and convenient SARS-CoV-2 virus detection is crucial for controlling and stopping the pandemics. Diagnosis of patients in the early stage infection are so far limited to viral nucleic acid or antigen detection in human nasopharyngeal swab or saliva samples. Here we developed a method for rapid and direct optical measurement of SARS-CoV-2 virus particles in one step nearly without any sample preparation using a spike protein specific nanoplasmonic resonance sensor. We demonstrate that we can detect as few as 30 virus particles in one step within 15 minutes and can quantify the virus concentration linearly in the range of 103vp/ml to 106vp/ml. Measurements shown on both generic microplate reader and a handheld smartphone connected device suggest that our low-cost and rapid detection method may be adopted quickly under both regular clinical environment and resource-limited settings.
Dichloroacetate reverses sepsis-induced hepatic metabolic dysfunction
Authors: Mainali Rabina , Zabalawi Manal , Long David , Buechler Nancy , Quillen Ellen , Key Chia-Chi , Zhu Xuewei , Parks John S. , Furdui Cristina , Stacpoole Peter W. , Martinez Jennifer , McCall Charles E. , Quinn Matthew A
Published: June 2020

Dramatic metabolic reprogramming between an anabolic resistance and catabolic tolerance state occurs within the immune system in response to systemic infection with the sepsis syndrome. While metabolic tissues such as the liver are subject to end-organ damage during sepsis and are the primary cause of sepsis death, how their metabolic and energy reprogramming during sepsis state ensures survival is unclear. Employing comprehensive metabolomic screening, targeted lipidomic screening, and transcriptional profiling in a mouse model of septic shock, we show that hepatocyte lipid metabolism, mitochondrial TCA energetics, and redox balance are significantly reprogramed after cecal ligation and puncture (CLP). We identify increases in TCA cycle metabolites citrate, cis-aconitate, and itaconate with reduced fumarate and triglyceride accumulation in septic hepatocytes. Transcription analysis of liver tissue supports and extends the hepatocyte findings. Strikingly, the administration of the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) reverses dysregulated hepatocyte metabolism and mitochondrial dysfunction. Our data indicate sepsis promotes hepatic metabolic dysfunction. Furthermore, our data indicate that targeting the mitochondrial PDC/PDK energy home-ostat rebalances transcriptional and metabolic manifestations of sepsis within the liver.
Instability with a purpose: how the visual brain makes decisions in a volatile world
Authors: Cao Robin , Pastukhov Alexander , Aleshin Stepan , Mattia Maurizio , Braun Jochen
Published: June 2020

In ambiguous or conflicting sensory situations, perception is often ‘multistable’ in that it changes abruptly at irregular intervals, shifting perpetually between distinct alternatives. Intriguingly, the interval statistics of these alternations exhibits quasi-universal characteristics, suggesting a general mechanism. Here we show that the stereotypical features of multistable perception, exemplified by binocular rivalry, are reproduced in detail by a hierarchical dynamics operating out of equilibrium. Its constitutive elements are discretely stochastic and idealize the metastability of cortical networks. Independent elements accumulate visual evidence at one level, while groups of coupled elements compete for dominance at another level. As soon as one group dominates perception, feedback inhibition suppresses supporting evidence. This mechanism is corroborated compellingly by unexpected serial dependencies of perceptual alternations. Moreover, it satisfies normative constraints of continuous decision-making. We conclude that multistable perception reflects decision-making in a volatile world: integrating evidence over space and time, choosing categorically between hypotheses, while concurrently evaluating alternatives.
Differential activity and expression of human 5β-reductase (AKR1D1) splice variants
Authors: Appanna Nathan , Gangitano Elena , Dempster Niall J , Morris Karen , George Sherly , Keevil Brian G , Penning Trevor M , Gathercole Laura L , Tomlinson Jeremy W , Nikolaou Nikolaos
Published: June 2020

Steroid hormones, including glucocorticoids and androgens, exert a wide variety of effects in the body across almost all tissues. The steroid A-ring 5β-reductase (AKR1D1) is expressed in human liver and testes, and three splice variants have been identified (AKR1D1-001, AKR1D1-002, AKR1D1-006). Amongst these,AKR1D1-002is the best described; it modulates steroid hormone availability and catalyses an important step in bile acid synthesis. However, specific activity and expression ofAKR1D1-001andAKR1D1-006are unknown.

AKR1D1-002, AKR1D1-001andAKR1D1-006were measured in human liver biopsies and human hepatoma cell lines by qPCR. Three-dimensional (3D) structures ofAKR1D1variants were determined usingin silicoapproaches.AKR1D1variants were over-expressed in HEK293 cells, and successful overexpression confirmed by qPCR and western blotting. Steroid hormone clearance was measured by mass spectrometry and ELISA, and steroid receptor activation determined by luciferase reporter assays.

AKR1D1-002andAKR1D1-001are expressed in human liver, and onlyAKR1D1-006is expressed in human testes. Following over-expression in HEK293 cells, AKR1D1-001 and AKR1D1-006 protein levels were lower than AKR1D1-002, but significantly increased following treatment with the proteasomal inhibitor, MG-132. AKR1D1-002 efficiently metabolised glucocorticoids and androgens and decreased receptor activation. AKR1D1-001 and AKR1D1-006 poorly metabolised dexamethasone, but neither protein metabolised cortisol, prednisolone or testosterone.

We have demonstrated the differential expression and role ofAKR1D1splice variants to regulate steroid hormone clearance and receptor activation. AKR1D1-002 is the predominant functional protein in steroidogenic and metabolic tissues. In addition, AKR1D1-001 and AKR1D1-006 may have a limited role in the regulation of synthetic glucocorticoid action.
The utility of native MS for understanding the mechanism of action of repurposed therapeutics in COVID-19: heparin as a disruptor of the SARS-CoV-2 interaction with its host cell receptor
Authors: Yang Yang , Du Yi , Kaltashov Igor A.
Published: June 2020

The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over six million cases and nearly four hundred thousand deaths reported world-wide by the end of May 2020. A rush to find the cures prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the non-covalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease of its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.

Abstract Figure