bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiari Malformation Type 1 and Syringomyelia in a Patient With Prior Surgically-Treated Sagittal Synostosis Effectively Treated With Posterior Cranial Vault Distraction Osteogenesis
Authors: Feller Christina N. , Jensen John N. , Lew Sean M.
Published: January 2021

The presenting report describes the use of a posterior cranial vault distraction procedure in resolving a Chiari malformation with associated syringomyelia following a surgically-treated nonsyndromic craniosynostosis. Chiari malformations are typically treated with posterior fossa decompression with or without expansion duraplasty. The objective of this report is to describe the effectiveness in resolving both Chiari malformation and secondary syringomyelia with posterior cranial vault distraction osteogenesis. A 5-year-old male, with a history of surgery for sagittal synostosis during infancy, presented with daily severe headaches and dysesthesias in the hands and feet. Imaging demonstrated a copper-beaten calvarium and a Chiari 1 malformation with a 7 mm diameter C4-T1 syrinx. He underwent posterior cranial vault distraction osteogenesis over 3 months to increase his intracranial volume. The patients’ headaches improved significantly, and his dysesthesias resolved postoperatively. A magnetic resonance imaging performed 7 months after completion of distraction demonstrated resolution of the Chiari malformation and decompression of his syrinx. A computed tomography scan at 9 months postdistraction showed resolution of the copper-beaten calvarium. Patients with a history of craniosynostosis can develop inadequate cranial volume over time due to abnormal skull growth, leading to secondary Chiari malformation with or without syringomyelia. Posterior vault distraction is an effective strategy to address these conditions and can be employed later in childhood to treat the underlying pathology. The mechanism potentially expands both calvarium and dura, which in turn addresses both the Chiari malformation and secondary syringomyelia.
Potential Complications With Cryopreserved Cadaveric Veins in Arteriovenous Loop Formation for Head and Neck Microvascular Reconstruction
Authors: Anderson Spencer R. , Harrison Lucas M. , Garret Candase C. , Wimalawansa Sunishka M. , Kadakia Sameep P.
Published: January 2021

Vessel depletion in the head and neck from radiation or previous surgical intervention adds to the operative complexity by limiting reconstructive options. Arteriovenous (AV) loop vascular grafts provide a conduit to bypass these nonviable local vessels to provide adequate blood flow. In certain situations, autologous donor vascular options are deficient or not readily available for creation of the AV loop. Cadaveric vein grafts provide an alternative option in these circumstances, but the efficacy and safety has not yet been delineated. In this study we discuss our experience utilizing cryopreserved cadaveric vein grafts for AV loop creation in head and neck reconstruction. In our initial cohort we aim to elucidate potential challenges and complications associated with the use of cadaveric vein grafts.
Transesophageal Echocardiography Simulator Training
Authors: Jujo Satoshi , Nakahira Atsushi , Kataoka Yuki , Banno Masahiro , Tsujimoto Yasushi , Tsujimoto Hiraku , Oikawa Sayaka , Matsui Hiroki , Berg Benjamin W.
Published: January 2021

Summary Statement

We aimed to assess the learning effects of novice transesophageal echocardiography (TEE) simulator training and to identify gaps in existing studies. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the learning effects of novice TEE training with versus without simulators, searching published articles and proceedings in 6 major databases in June 2019. We included 9 RCTs (268 participants). Compared with nonsimulator training, TEE simulator training resulted in higher skill and knowledge posttraining test scores with large effect sizes (standardized mean difference = 0.81 for skill, 1.61 for knowledge; low-certainty evidence) and higher training satisfaction with a small effect size (standardized mean difference = 0.36; very low-certainty evidence). No RCTs reported training budget or patient outcomes. Additional well-designed studies with low risk of bias and large sample sizes are needed to provide reliable and robust findings and develop more effective TEE simulation-based training curricula.
Life-Saving Procedures Performed While Wearing CBRNe Personal Protective Equipment
Authors: Mormando Giulia , Paganini Matteo , Alexopoulos Chiara , Savino Sandro , Bortoli Nicola , Pomiato Daniele , Graziano Alessandro , Navalesi Paolo , Fabris Fabrizio
Published: January 2021

Introduction

Chemical-biological-radiological-nuclear-explosive (CBRNe) are complex events. Decontamination is mandatory to avoid harm and contain hazardous materials, but can delay care. Therefore, the stabilization of patients in the warm zone seems reasonable, but research is limited. Moreover, subjects involved in biological events are considered infectious even after decontamination and need to be managed while wearing personal protective equipment (PPE), as seen with Ebola and COVID-19 pandemic. With this simulation mannequin trial, we assessed the impact of CBRNe PPE on cardiopulmonary resuscitation and combat casualty care procedures.

Methods

We compared procedures performed by emergency medicine and anesthesiology senior residents, randomized in 2 groups (CBRNe PPE vs. no PPE). Chest compression (CC) depth was defined as the primary outcome. Time to completion was calculated for the following: tourniquet application; tension pneumothorax needle decompression; peripheral venous access (PVA) and intraosseous access positioning; and drug preparation and administration. A questionnaire was delivered to evaluate participants' perception.

Results

Thirty-six residents participated. No significant difference between the groups in CC depth (mean difference = 0.26 cm [95% confidence interval = −0.26 to 0.77 cm, P = 0.318]), as well as for CC rate, CC complete release, and time for drugs preparation and administration was detected. The PPE contributed to significantly higher times for tourniquet application, tension pneumothorax decompression, peripheral venous access, and intraosseous access positioning. The residents found simulation relevant to the residencies' core curriculum.

Conclusions

This study suggests that cardiopulmonary resuscitation can be performed while wearing PPE without impacting quality, whereas other tasks requiring higher dexterity can be significantly impaired by PPE.

Trial Registration Number: NCT04367454, April 29, 2020 (retrospectively registered).
Association of HHV-6 With Outcomes in CMV-seronegative Liver Transplant Recipients With CMV-seropositive Donors Receiving Preemptive Antiviral Therapy
Authors: Singh Nina , Winston Drew J. , Razonable Raymund R. , Lyon G. Marshall , Huang Meei-Li , Jerome Keith R. , Silveira Fernanda P. , Wagener Marilyn M. , Limaye Ajit P.
Published: January 2021

Background.

Risk factors, virological parameters, and outcomes associated with HHV-6 viremia in high-risk donor CMV-seropositive and recipient CMV-seronegative (D+R–) liver transplant recipients in the current era are incompletely defined.

Methods.

The study population consisted of patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus valganciclovir prophylaxis for CMV prevention in D+R– liver transplant recipients. Weekly blood samples through 100 d in the PET group were tested for HHV-6 viremia using a real-time quantitative polymerase chain reaction. Assessments included virological characteristics and relationship with CMV, risk factors, and impact of HHV-6 viremia with outcomes through 12 mo posttransplant.

Results.

HHV-6 viremia at any level developed in 42% (40 of 96). Older patient age (P = 0.03), longer hospitalization (P = 0.015), and ICU stay at transplantation (P = 0.029) were significantly associated with high-grade viremia. Concurrent HHV-6 and CMV viremia was associated with earlier onset of HHV-6 viremia (P = 0.004), higher HHV-6 area under the curve (P = 0.043), and higher peak HHV-6 viral load (P = 0.006) versus HHV-6 viremia alone. High-grade viremia was independently associated with biopsy-proven rejection within 12 mo (P = 0.045) posttransplant.

Conclusions.

Among D+R– liver transplant recipients receiving valganciclovir as PET, high-grade HHV-6 viremia was associated with increased age and critical illness in ICU at time of transplant and was independently associated with allograft rejection.
A Pre-TACE Radiomics Model to Predict HCC Progression and Recurrence in Liver Transplantation: A Pilot Study on a Novel Biomarker
Authors: Ivanics Tommy , Salinas-Miranda Emmanuel , Abreu Phillipe , Khalvati Farzad , Namdar Khashayar , Dong Xin , Deniffel Dominik , Gorgen Andre , Erdman Lauren , Jhaveri Kartik , Haider Masoom , Veit-Haibach Patrick , Sapisochin Gonzalo
Published: January 2021

Background.

Despite transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), a significant number of patients will develop progression on the liver transplant (LT) waiting list or disease recurrence post-LT. We sought to evaluate the feasibility of a pre-TACE radiomics model, an imaging-based tool to predict these adverse outcomes.

Methods.

We analyzed the pre-TACE computed tomography images of patients waiting for a LT. The primary endpoint was a combined event that included waitlist dropout for tumor progression or tumor recurrence post-LT. The radiomic features were extracted from the largest HCC volume from the arterial and portal venous phase. A third set of features was created, combining the features from these 2 contrast phases. We applied a least absolute shrinkage and selection operator feature selection method and a support vector machine classifier. Three prognostic models were built using each feature set. The models’ performance was compared using 5-fold cross-validated area under the receiver operating characteristic curves.

Results

. Eighty-eight patients were included, of whom 33 experienced the combined event (37.5%). The median time to dropout was 5.6 mo (interquartile range: 3.6–9.3), and the median time for post-LT recurrence was 19.2 mo (interquartile range: 6.1–34.0). Twenty-four patients (27.3%) dropped out and 64 (72.7%) patients were transplanted. Of these, 14 (21.9%) had recurrence post-LT. Model performance yielded a mean area under the receiver operating characteristic curves of 0.70 (±0.07), 0.87 (±0.06), and 0.81 (±0.06) for the arterial, venous, and the combined models, respectively.

Conclusions.

A pre-TACE radiomics model for HCC patients undergoing LT may be a useful tool for outcome prediction. Further external model validation with a larger sample size is required.
Publication Rate of Abstracts Presented at the North American Neuro-Ophthalmology Society Annual Meeting From 2008 to 2017
Authors: Yuan Po Hsiang (Shawn) , MacLean Luke J. , Li Erica A. , Yin Shelly , Micieli Jonathan A.
Published: January 2021

Background:

Conference abstracts serve an important role in the timely dissemination of scientific and clinical advancements, but most fail to be published. The goal of this study was to investigate the publication rate and factors associated with publication of abstracts presented at the North American Neuro-Ophthalmology Society (NANOS) Annual Meeting over a 10-year period.

Methods:

NANOS Annual Meeting abstracts from 2008 to 2017 were extracted and categorized into Walsh presentations, scientific platforms, or poster presentations. An original automated web scraping program was validated to search PubMed, Embase, Medline, and Google Scholar for publications. Publication date, journal, authors, study type, multicenter involvement, and financial disclosures were retrieved.

Results:

A total of 195 Walsh presentations, 231 scientific platform presentations, and 1735 scientific posters were included in the study with an overall publication rate of 31.5% (681/2,161). This was stable over the study period. Publication was the highest for scientific platforms (67.1%), followed by Walsh abstracts (36.4%) and poster presentations (27.2%). Multivariable analysis identified 3–4 authors, 5 or more authors, basic science, and sample size of 100 or more significantly correlated with subsequent publication. The top 3 countries for NANOS submissions were the United States, Canada, and South Korea, and the most frequent journal of publication was the Journal of Neuro-Ophthalmology.

Conclusions:

Publication rate of NANOS abstracts is comparable to other conferences in ophthalmology and the neurological sciences. Conference attendees should be aware that more than two-thirds of abstracts fail to be published and publication rates vary widely by type of submission.
Hospital-Acquired Pressure Injuries and Acute Skin Failure in Critical Care
Authors: Pittman Joyce , Beeson Terrie , Dillon Jill , Yang Ziyi , Mravec Michelle , Malloy Caeli , Cuddigan Janet
Published: January 2021

PURPOSE

The purpose of this study was to examine clinical characteristics and risk factors for critically ill patients who develop pressure injuries and identify the proportion of validated unavoidable pressure injuries associated with the proposed risk factors for acute skin failure (ASF).

DESIGN:

Retrospective case-control comparative study.

SUBJECTS AND SETTING:

The sample comprised adult critically ill participants hospitalized in critical care units such as surgical, trauma, cardiovascular surgical, cardiac, neuro, and medical intensive care and corresponding progressive care units in 5 acute care hospitals within a large Midwestern academic/teaching healthcare system. Participants who developed hospital-acquired pressure injuries (HAPIs) and patients without HAPIs (controls) were included.

METHODS:

A secondary analysis of data from a previous study with HAPIs and matching data for the control sample without HAPIs were obtained from the electronic health record. Descriptive and multivariate logistic regression analyses were conducted.

RESULTS:

The sample comprised 475 participants; 165 experienced a HAPI and acted as cases, whereas the remaining 310 acted as controls. Acute Physiology and Chronic Health Evaluation (APACHE II) mean score (23.8, 8.7%; P < .001), mortality (n = 45, 27.3%; P = .002), history of liver disease (n = 28, 17%; P < .001), and unintentional loss of 10 lb or more in 1 month (n = 20, 12%; P = .002) were higher in the HAPI group. Multivariate logistic regression analysis identified participants with respiratory failure (odds ratio [OR] = 3.00; 95% confidence interval [CI], 1.27-7.08; P = .012), renal failure (OR = 7.48; 95% CI, 3.49-16.01; P < .001), cardiac failure (OR = 4.50; 95% CI, 1.76-11.51; P = .002), severe anemia (OR = 10.89; 95% CI, 3.59-33.00; P < .001), any type of sepsis (OR = 3.15; 95% CI, 1.44-6.90; P = .004), and moisture documentation (OR = 11.89; 95% CI, 5.27-26.81; P <.001) were more likely to develop a HAPI. No differences between unavoidable HAPI, avoidable HAPI, or the control group were identified based on the proposed ASF risk factors.

CONCLUSION:

This study provides important information regarding avoidable and unavoidable HAPIs and ASF. Key clinical characteristics and risk factors, such as patient acuity, organ failure, tissue perfusion, sepsis, and history of prior pressure injury, are associated with avoidable and unavoidable HAPI development. In addition, we were unable to support a relationship between unavoidable HAPIs and the proposed risk factors for ASF. Unavoidability of HAPIs rests with the documentation of appropriate interventions and not necessarily with the identification of clinical risk factors.
Suicide prevention efforts in the United States and their effectiveness
Authors: Barnhorst Amy , Gonzales Hilary , Asif-Sattar Rameesha
Published: January 2021

Purpose of review

Suicide is a serious public health problem in the United States, and suicide rates have been increasing for more than a decade. Rural areas are more impacted than urban areas, reinforcing that social, cultural, and economic factors contribute to risk. This article reviews recent work about these contributors to suicide and how they may inform prevention efforts.

Recent findings

Current research has shown that suicide is more than a mental health problem with a psychiatric or medical solution. Universal screening and referral by gatekeepers target a large group with a low baseline risk, and there are few treatments proven to reduce death by suicide, as well as a severe shortage of mental health providers in the United States to provide them. Instead, suicide prevention polices can target various other factors that contribute to elevated suicide risk at the population level, including reducing socioeconomic deprivation and access to firearms, both of which are often higher in rural areas. Internet-based interventions also hold promise as they are highly scalable, accessible almost anywhere, and often anonymous.

Understanding factors that increase suicide risk guide development of evidence-based policies targeted at high-risk groups. Population-level interventions should be developed in collaboration with the target audience for cultural appropriateness.
Citrobacter koseri stimulates dendritic cells to induce IL-33 expression via abundant ATP production
Authors: Kataoka Hideo , Mori Taiki , Into Takeshi
Published: January 2021

Introduction.Food allergies (FAs) occur due to intestinal immune dysfunction elicited by dysbiotic conditions. It was previously determined by us thatCitrobacterspecies propagate in the faeces of mice with FAs and worsen allergic symptoms by inducing the allergenic cytokine IL-33. Dendritic cells can play important roles in regulation of FA responses.

Hypothesis.Citrobacterspecies propagating in intestines of mice worsen allergic symptoms by stimulating dendritic cells to induce IL-33 expression.

Aim.The aim of the present study was to analyse whetherC. koseristimulates dendritic cells to induce IL-33 expression.

Methodology.IL-33 expression was evaluated in a DC2.4 mouse dendritic cell line stimulated by live or heat-inactivatedC. koseriJCM1658, ATP, LPS extracted fromC. koseriJCM1658 or other enterobacteria by real-time PCR. The ATP concentration and number of live bacteria in the culture supernatant were measured simultaneously.

Results.LiveC. koseriJCM1658 induced higher levels of IL-33 expression than other enterobacteria tested, but such a response was not elicited by heat-inactivatedC. koseriJCM1658. LPS extracted fromC. koseriJCM1658 did not induce IL-33 expression and suppressed liveC. koseriJCM1658-induced IL-33 expression via the activation of Toll-like receptor 4 signalling. Furthermore, ATP produced byC. koseriJCM1658 stimulated dendritic cells to induce IL-33 expression by stimulating the P2X7receptor, and LPS attenuated extracellular ATP-induced IL-33 expression.C. koseriJCM1658 was observed to proliferate more vigorously and produce more ATP than other enterobacteria.

Conclusion.C. koseriacts as an allergenic bacterium through ATP production, stimulating dendritic cells to induce IL-33 expression, while LPS released from inactivatedC. koseriJCM1658 attenuates this allergenicity.
Late Pleistocene palaeoecology and phylogeography of woolly rhinoceroses
Authors: Rey-Iglesia Alba , Lister Adrian M. , Stuart Anthony J. , Bocherens Hervé , Szpak Paul , Willerslev Eske , Lorenzen Eline D.
Published: January 2021

The woolly rhinoceros (Coelodonta antiquitatis) was a cold-adapted herbivore, widely distributed from western Europe to north-east Siberia during the Late Pleistocene. Previous studies associate the extinction of the species ~14,000 years before present to climatic and vegetational changes, and suggest that later survival of populations in north-east Siberia may relate to the later persistence of open vegetation in that region. Here, we analyzed carbon (δ13C) and nitrogen (δ15N) stable isotopes and mitochondrial DNA sequences to elucidate the evolutionary ecology of the species. Our dataset comprised 286 woolly rhinoceros isotopic records, including 192 unpublished records, from across the species range, dating from >58,60014C years to ~14,000 years before present. Crucially, we present the first 71 isotopic records available to date of the 15,000 years preceding woolly rhinoceros extinction. The data reveal ecological flexibility and geographical variation in woolly rhinoceros stable isotope compositions through time. In north-east Siberia, we detectedδ15N stability through time. This could reflect long-term environmental stability, and might have enabled the later survival of the species in the region. To further investigate the palaeoecology of woolly rhinoceroses, we compared their isotopic compositions with that of other contemporary herbivores. This analysis suggests possible niche partitioning between woolly rhinoceros and both horse (Equus spp.) and woolly mammoth (Mammuthus primigenius), and isotopic similarities between woolly rhinoceros and both musk ox (Ovibos moschatus) and saiga (Saiga tatarica) at different points in time. To provide phylogeographical context to the isotopic data, we analyzed 61 published mitochondrial control region sequences. The data show a lack of geographic structuring; we found three haplogroups with overlapping distributions, all of which show a signal of expansion during the Last Glacial Maximum. Furthermore, our genetic findings support the notion that environmental stability in Siberia had an impact on the paleoecology of woolly rhinoceroses in the region. Our study highlights the utility of combining stable isotopic records with ancient DNA to advance our knowledge of the evolutionary ecology of past populations and extinct species.
Intermittent radiotherapy as alternative treatment for recurrent high grade glioma: A modelling study based on longitudinal tumor measurements
Authors: Brüningk Sarah C. , Peacock Jeffrey , Whelan Christopher J. , Yu Hsiang-Hsuan M. , Sahebjam Solmaz , Enderling Heiko
Published: January 2021

Recurrent high grade glioma patients face a poor prognosis for which no curative treatment option currently exists. In contrast to prescribing high dose hypofractionated stereotactic radiotherapy (HFSRT, ≥ 6 Gyx5 in daily fractions) with debulking intent, we suggest a personalized treatment strategy to improve tumor control by delivering intermittent high dose treatment (iRT, ≥ 6 Gyx1 every six weeks). We performed a simulation analysis to compare HFSRT, iRT and iRT plus boost (≥ 6 Gyx3 in daily fractions at time of progression) based on a mathematical model of tumour growth, radiation response and patient-specific evolution of resistance to additional treatments (pembrolizumab and bevacizumab). Model parameters were fitted from tumour growth curves of 16 patients enrolled in the phase 1 NCT02313272 trial that combined HFSRT with bevacizumab and pembrolizumab. Then, iRT +/-boost treatments were simulated and compared to HFSRT based on time to tumor regrowth. The modelling results demonstrated that iRT+boost(-boost) treatment was equal or superior to HFSRT in 15(11) out of 16 cases and that patients that remained responsive to pembrolizumab and bevacizumab would benefit most from iRT. Time to progression could be prolonged through the application of additional, intermittently delivered fractions. iRT hence provides a promising treatment option for recurrent high grade glioma patients.
A Fractional Order Dengue Fever Model in the Context of Protected Travellers
Authors: Bonyah E. , Juga M. L. , Chukwu C. W. , Fatmawati
Published: January 2021

Climate changes are affecting the control of many vector-borne diseases, particularly in Africa. In this work, a dengue fever model with protected travellers is formulated. Caputo-Fabrizio operator is utilized to obtain some qualitative information about the disease. The basic properties and the reproduction number is studied. The two steady states are determined and the local stability of the states are found to be asymptotically stable. The fixed pointed theory is made use to obtain the existence and uniqueness of solutions of the model. The numerical simulation suggests that the fractional-order affects the dynamics of dengue fever.
Native structure of the RhopH complex, a key determinant of malaria parasite nutrient acquisition
Authors: Ho Chi-Min , Jih Jonathan , Lai Mason , Li Xiaorun , Goldberg Daniel E. , Beck Josh R. , Zhou Z. Hong
Published: January 2021

The RhopH complex is implicated in malaria parasites’ ability to invade and create new permeability pathways in host erythrocytes, but its mechanisms remain poorly understood. Here we enrich the endogenous RhopH complex in a native soluble form, comprising RhopH2, CLAG3.1 and RhopH3, directly from parasite cell lysates and determine its atomic structure using cryo electron microscopy, mass spectrometry, and the cryoID program. This first direct observation of an exportedP. falciparumtransmembrane protein—in a soluble, trafficking state and with atomic details of buried putative membrane-insertion helices—offers insights into assembly and trafficking of RhopH and other parasite-derived complexes to the erythrocyte membrane. Our study demonstrates the potential endogenous structural proteomics approach holds for elucidating the molecular mechanisms of hard-to-isolate complexes in their native, functional forms.
Climate warming changes synchrony of plants and pollinators
Authors: Freimuth Jonas , Bossdorf Oliver , Scheepens J. F. , Willems Franziska M.
Published: January 2021

Climate warming changes the phenology of many species. When interacting organisms respond differently, climate change may disrupt their interactions and affect the stability of ecosystems. Here, we used GBIF occurrence records to examine phenology trends in plants and their associated insect pollinators in Germany since the 1980s. We found strong phenological advances in plants, but differences in the extent of shifts among pollinator groups. The temporal trends in plant and insect phenologies were generally associated with interannual temperature variation, and thus likely driven by climate change. When examining the synchrony of species-level plant-pollinator interactions, their temporal trends differed among pollinator groups. Overall, plant-pollinator interactions become more synchronized, mainly since the phenology of plants responded more strongly to climate change than that of the pollinators. However, if the observed trends continue, many interactions may become more asynchronous again in the future. Our study suggests that climate change affects the phenologies of both plants and insects, and that it also influences the synchrony of plant-pollinator interactions.
Distinct T cell chromatin landscapes in scleroderma subtypes
Authors: Dou Diana R. , Zhao Yang , Abe Brian , Li Rui , Zaba Lisa C. , Aren Kathleen , Carns Mary , Chung Lorinda S. , Hinchcliff Monique , Chang Howard Y.
Published: January 2021

Systemic sclerosis (SSc; scleroderma) is an autoimmune rheumatic disease that primarily affects biological females whose pathogenesis is poorly understood. The clinical hallmark is hardening of the skin, but internal organ dysfunction is the leading cause of death. Diagnosis and treatment are complicated by heterogeneity within the disease including variable lethality, fibrosis severity, serum autoantibody production, and internal organ involvement. Important gaps remain in our knowledge of the exact molecular and cellular pathways underlying distinct SSc subtypes. Herein, we identify genome-wide chromatin accessibility profiles of peripheral CD4+T cells to distinguish and better understand the observed heterogeneity in SSc patients. We identify a link between the presence of serum anticentromere autoantibodies (ACA) and elevated levels of T helper 2 (Th2) cells and increased chromatin access at gene loci encoding fibrosis-driving Th2 cytokines IL4, IL13, and IL4 receptor. Biological sex followed by autoantibody type are the predominant variables associated with differences in CD4+T cell epigenomic profiles, while mycophenolate mofetil treatment appeared to have no effect. These results suggest new mechanistic basis and therapeutic strategies to address SSc, especially the anti-ACA+ subset of patients who more frequently develop pulmonary arterial hypertension.
The pathway of starch synthesis inArabidopsis thalianaleaves
Authors: Fünfgeld Maximilian M.F.F. , Wang Wei , Ishihara Hirofumi , Arrivault Stéphanie , Feil Regina , Smith Alison M. , Stitt Mark , Lunn John E. , Niittylä Totte
Published: January 2021

Many plants accumulate transitory starch reserves in their leaves during the day to buffer their carbohydrate supply against fluctuating light conditions, and to provide carbon and energy for survival at night. It is universally accepted that transitory starch is synthesized from ADP-glucose (ADPG) in the chloroplasts. However, the consensus that ADPG is made in the chloroplasts by ADPG pyrophosphorylase has been challenged by a controversial proposal that ADPG is made primarily in the cytosol, probably by sucrose synthase (SUS), and then imported into the chloroplasts. To resolve this long-standing controversy, we critically re-examined the experimental evidence that appears to conflict with the consensus pathway. We show that when precautions are taken to avoid artefactual changes during leaf sampling,Arabidopsis thalianamutants that lack SUS activity in mesophyll cells (quadruplesus1234) or have no SUS activity (sextuplesus123456) have wild-type levels of ADPG and starch, while ADPG is 20 times lower in thepgmandadg1mutants that are blocked in the classical pathway of starch synthesis. We conclude that the ADPG needed for starch synthesis in leaves is synthesized primarily by ADPG pyrophosphorylase in the chloroplasts.

Significance statement

Mutant analysis shows that sucrose synthase makes no significant contribution to transitory starch synthesis in Arabidopsis leaves, resolving a 20-year old controversy about one of the most important pathways of photosynthetic metabolism.
DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and in response to immunotherapy
Authors: Baldwin Louise A. , Bartonicek Nenad , Yang Jessica , Wu Sunny Z. , Deng Niantao , Roden Daniel L. , Chan Chia-Ling , Al-Eryani Ghamdan , Zanker Damien J. , Parker Belinda S. , Swarbrick Alexander , Junankar Simon
Published: January 2021

Cancers evade the immune system in order to grow or metastasise through the process of cancer immunoediting. While immune checkpoint inhibitors have been effective for reactivating tumour immunity in some types of cancer, many other solid cancers, including breast cancer, remain largely non-responsive. Understanding the way non-responsive cancers evolve to evade immunity, what resistance pathways are activated and whether this occurs at the clonal level will improve immunotherapeutic design. We tracked cancer cell clones during the immunoediting process and determined clonal transcriptional profiles that allow immune evasion in murine mammary tumour growth in response to immunotherapy with anti-PD1 and anti-CTLA4. Clonal diversity was significantly restricted by immunotherapy treatment in both primary tumours and metastases. These findings demonstrate that immunoediting selects for pre-existing breast cancer cell populations and that immunoediting is not static, it is ongoing during metastasis and immunotherapy treatment. Isolation of immunotherapy resistant clones revealed unique and overlapping transcriptional signatures. The overlapping gene signature was associated with poor survival of basal-like breast cancer patients in two cohorts. At least one of these overlapping genes has an existing small molecule that can potentially be used to improve immunotherapy response.
Biop-C: A Method for Chromatin Interactome Analysis of Solid Cancer Needle Biopsy Samples
Authors: Animesh Sambhavi , Choudhary Ruchi , Ng Xin Yi , Tay Joshua Kai Xun , Chong Wan-Qin , Goh Boon Cher , Fullwood Melissa Jane
Published: January 2021

A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method adapted to solid cancer needle biopsy samples. Here we developed Biop-C, a modifiedin situHi-C method, and applied it to characterize three nasopharyngeal cancer patient samples. We identified Topologically-Associated Domains (TADs), chromatin interaction loops, and Frequently Interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from Biop-C heat maps. Our results demonstrate the utility of our Biop-C method in investigating the 3D genome organization in solid cancers, and the importance of 3D genome organization in regulating oncogenes in nasopharyngeal cancer.
Cell-Free Characterization of Coherent Feed-Forward Loop-Based Synthetic Genetic Circuits
Authors: Pieters Pascal A. , Nathalia Bryan L. , van der Linden Ardjan J. , Yin Peng , Kim Jongmin , Huck Wilhelm T.S. , de Greef Tom F. A.
Published: January 2021

Regulatory pathways inside living cells employ feed-forward architectures to fulfill essential signal processing functions that aide in the interpretation of various types of inputs through noise-filtering, fold-change detection and adaptation. Although it has been demonstrated computationally that a coherent feed-forward loop (CFFL) can function as noise filter, a property essential to decoding complex temporal signals, this motif has not been extensively characterized experimentally or integrated into larger networks. Here we use post-transcriptional regulation to implement and characterize a synthetic CFFL in anEscherichia colicell-free transcription-translation system and build larger composite feed-forward architectures. We employ microfluidic flow reactors to probe the response of the CFFL circuit using both persistent and short, noise-like inputs and analyze the influence of different circuit components on the steady-state and dynamics of the output. We demonstrate that our synthetic CFFL implementation can reliably repress background activity compared to a reference circuit, but displays low potential as a temporal filter, and validate these findings using a computational model. Our results offer practical insight into the putative noise-filtering behavior of CFFLs and show that this motif can be used to mitigate leakage and increase the fold-change of the output of synthetic genetic circuits.
Real-Time Three-Dimensional Tracking of Single Vesicles Reveals the Abnormal Motion and Vesicle Pools of Synaptic Vesicles in Neurons of Huntington’s Disease Mice
Authors: Chen Sidong , Yoo Hanna , Li Chun Hei , Park Chungwon , Tan Li Yang , Jung Sangyong , Park Hyokeun
Published: January 2021

Although defective synaptic transmission was suggested to play a role in neurodegenerative diseases, the dynamics and vesicle pools of synaptic vesicles during neurodegeneration remain elusive. Here, we performed real-time three-dimensional tracking of single synaptic vesicles in cortical neurons from a mouse model of Huntington’s disease (HD). Vesicles in HD neurons had a larger net displacement and radius of gyration compared with wild-type neurons. Vesicles with a high release probability (Pr) were interspersed with low-Prvesicles in HD neurons, whereas high-Prand low-Prvesicle pools were spatially separated in wild-type neurons. Non-releasing vesicles in HD neurons had an abnormally high prevalence of irregular oscillatory motion. These abnormal dynamics and vesicle pools were rescued by overexpressing Rab11, and the abnormal irregular motion was rescued by jasplakinolide. These results suggest the abnormal dynamics and vesicle pools of synaptic vesicles in the early stages of HD, suggesting a possible pathogenic mechanism of neurodegenerative diseases.
Is earlier reproduction associated with higher or lower survival? Antagonistic results between individual and population scales in the blue tit
Authors: Bastianelli Olivier , Charmantier Anne , Biard Clotilde , Bonamour Suzanne , Teplitsky Céline , Robert Alexandre
Published: January 2021

Although it has been shown that phenology can respond to temporal environmental variation in free ranging populations of several species, little is known about the mechanisms of these responses and their effects on demography, and in particular on survival. Exploring phenological responses and their associated consequences on survival can be achieved at two distinct scales: the population scale, which focusses on a set of common responses to environmental conditions, and the individual scale, focusing on the relative position of each individual in the distribution of survival and phenology under particular conditions. In this study, we apply capture-mark-recapture multistate modelling on a 38-year monitoring dataset of blue tits (Cyanistes caeruleus) to investigate the effects of breeding phenology and some demographic covariates (breeding density, average and individual breeding success) on adult survival, at both population and individual scales. Our analysis revealed that (i) at the population scale, early breeding years are followed by lower average adult survival. (ii) At the individual level, earlier breeders within the population have higher subsequent survival than later breeders, although this relationship is reversed in years with very harsh conditions, e.g. warm spring and high breeding density. (iii) High individual relative breeding success is also associated with higher subsequent survival and explains more survival variation than relative phenology. Overall, our study indicates that, although earlier breeding is associated with a survival cost at the population level, substantial intrapopulation hererogeneity shapes a positive association between earlier breeding, breeding success and survival at the individual level.
anonymizeBAM: Versatile anonymization of human sequence data for open data sharing
Authors: Ziegenhain Christoph , Sandberg Rickard
Published: January 2021

The risks associated with re-identification of human genetic data are severely limiting open data sharing in life sciences. Here, we developedanonymizeBAM, a versatile tool for the anonymization of genetic variant information present in sequence data. ApplyinganonymizeBAMto single-cell RNA-seq and ATAC-seq datasets confirmed the complete removal of donor-related genetic information. Therefore, the accurate generation of de-identified sequence data will re-enable open sharing in sequencing-based studies for improved transparency, reproducibility, and innovation.
Corporate reporting to the crown: a longitudinal case from colonial Africa
Authors: Power Sean Bradley , Brennan Niamh M.
Published: January 2021

Purpose

A royal charter of incorporation imposing public benefit/social responsibilities established the privately owned British South Africa Company (BSAC), in return for power to exploit a huge territory using low-cost local labour. This study explores the dual principal–agent problem of how the BSAC used annual report narratives to report on its conflicting economic responsibilities to investors versus its public benefit charter responsibilities to the British Crown.

Design/methodology/approach

Having digitised the dataset, the research analyses narratives from 29 BSAC annual reports spanning a continuous 35-year royal charter period, using computer-aided keyword content analysis to identify economic-orientated versus public benefit-orientated annual report narratives. The research analyses how the annual report narratives shifted according to four key contextual periods by reference to the changing influence of private investors versus the British Crown.

Findings

There are two key findings. First, economic primacy. At no point do public benefit disclosures outweigh economic disclosures. Second, the BSAC's meso-corporate context and macro-social/political context can explain patterns in public benefit disclosures. The motivation for producing public benefit information is not altruism. Rather, commercial interests motivate disclosure. The BSAC used its annual reports to sustain what proved ultimately unsustainable – royal charter-style colonialism.

Originality/value

This accounting history study contributes to an understanding of corporate narrative reporting using one of the earliest known cases of such analysis and shows how accounting plays a central role in facilitating a company in sustaining its interests. This 100-year lookback may be a portend of the future for modern-day annual report corporate social responsibility narratives in, say, mining and oil and gas company corporate reports, especially if these natural resources run out.
Social integration through social connection in everyday life. Residents' experiences during the COVID-19 pandemic in SällBo collaborative housing, Sweden
Authors: Arroyo Ivette , Montesino Norma , Johansson Erik , Yahia Moohammed Wasim
Published: January 2021

Purpose

The aim of this article is to explore the everyday life experiences of elderly (+70 years) living with young locals and refugees in a collaborative housing project before and during the COVID-19 pandemic in Sweden. The paper discusses the importance of the spatial dimension in the conceptualization of social integration.

Design/methodology/approach

The main method is a qualitative case study based on observations of settings, document/video analysis, online diary entries made by ten residents and eight semi- structured interviews conducted with the residents.

Findings

SällBo was conceived as a new type of collaborative housing in which elderly, young locals and refugees share common spaces with the aim of enabling social integration. In this context, COVID-19 interrupted the ongoing processes of living together after four months of moving to the house. The three main themes that emerge from the empirical material are (1) changes in the use of common spaces and social interactions, (2) residents' resilient coping responses during the pandemic and (3) insights for future design of collaborative housing based on their experience. The pandemic caused a moment of institutional vacuum, which triggered the agency of the residents whilst developing social bonds and social bridges among them.

Social implications

Social connection created in everyday life at SällBo's common spaces has triggered processes of social integration.

Originality/value

The ongoing processes of social integration have included the spatial dimension. We understand social integration as a process that involves people from different generations and ethnical backgrounds, which takes place in common spaces and everyday life as different modes of socialization.
Customer process-centric artefacts: a literature review
Authors: Palvölgyi Elisabeth Zsoka , Moormann Jürgen
Published: January 2021

Purpose

Companies that strive to provide customers with value in their processes benefit from artefacts that allow them to better understand customer processes (CPs) and to influence CPs in ways that are valuable for customers. Such CP-centric artefacts (CPCAs) carry various labels across research fields, which inhibit their application or utilization for developing further artefacts. This study provides a structured overview of existing CPCAs and investigates which research foundations promote their development.

Design/methodology/approach

Twenty-five CP-related keyword combinations are applied in several iterations using multiple (meta) search engines to identify papers on CPCAs across different research streams. Introduced research frameworks organize the identified artefacts and indicate research gaps and reasons why some approaches are more successful in developing CPCAs than others.

Findings

Existing CPCAs cover different aspects of CPs and utilize contextual factors of CPs to varying degrees to analyse or influence CPs. Research gaps are identified that indicate opportunities to develop further CPCAs. Taking instantiated methods in combination with CP-related descriptive knowledge as a foundation yields the highest potential for generating beneficial CPCAs.

Originality/value

This paper contributes to CP management literature by offering a foundation for the generation of CPCAs suitable for analysing and influencing CPs of end-consumers. This supports the establishment of a CP management aiming at optimizing both, interlinked business processes and CPs.
Compact multiple electromagnetic band gap (EBG) cells based ultra wide band (UWB) filter with improved stop-band characteristics
Authors: Molimoli Hajamohideen Masood , Balakrishanapillai Suseela Sreeja
Published: January 2021

Purpose

The purpose of the study is – in Microwave filter design, the performances of passive components are deteriorated by parasitics at gigahertz (GHz) frequency range. A compact and multi-stack electromagnetic band gap (EBG) structure is proposed with improved stop band characteristics at GHz frequency range in this work. This paper proposes a new design for ultra wide band pass filter (resonator BPF) with periodically loaded one-dimensional EBG to achieve the harmonic suppression. This basic EBG structure is developed with combination of a signal strip and ground plane in the slotted section. The resonator BPF is loaded with one EBG, two EBG and three EBGs to improve the stop-band rejection.

Design/methodology/approach

The proposed filter is with multi-stack EBG cell for achieving good pass band and stop bands performance. Circuit model is analyzed in Section 2. Section 3 discuses band pass filter loaded with one EBG. In Sections 4 and 5, filter with two and three EBG loaded resonators are discussed, respectively. Section 6 is concluded with comparison of simulation and measured results.

Findings

The stop-band rejection is 20 dB, 40 dB and 50 dB, respectively, in the frequency range of 6 GHz to 20 GHz. The simulation analysis is carried out with advanced system design software. To validate the simulation results, proposed structure is fabricated, and results are found to be in good agreement.

Originality/value

This paper accounts for designing resonator BPF, which has slow wave pass band and stop band characteristics. Second and third harmonics are suppressed using multi-stack EBG. Various stacks with basic designs are proposed and improved results have been demonstrated which is open for future research.
ESG and corporate financial performance: the mediating role of green innovation: UK common law versus Germany civil law
Authors: Chouaibi Salim , Chouaibi Jamel , Rossi Matteo
Published: January 2021

Purpose

The purpose of this paper is to investigate the direct and indirect links between environmental, social and governance (ESG) practices and financial performance using the mediate role of green innovation.

Design/methodology/approach

To test the current study hypotheses, the authors applied linear regressions with a panel data using the Thomson Reuters ASSET4 and Bloomberg database from a sample of 115 UK and 90 Germany companies selected from the ESG index over the period 2005–2019.

Findings

The results show that the strengths ESG increase the firm value and the weaknesses decrease it. In addition, the authors find that green innovation fully mediates the relationship between ESG practices and financial performance in UK and Germany.

Practical implications

The findings provide interesting implications to academics practitioners and regulators who are interested in discovering ESG score, financial performance and green innovation. The results also provide insights to regulators and the board of directors on future growth opportunities for the company and the country.

Originality/value

This study is unique in examining the mediation effect of green innovation on the relationship between ESG practices and financial performance.