bluuebunny/crossref_metadata_2025 huggingface dataset:
Building the mega single-cell transcriptome ocular meta-atlas
Authors: Swamy Vinay S , Fufa Temesgen D , Hufnagel Robert B , McGaughey David M
Published: October 2021

Background: The development of highly scalable single-cell transcriptome technology has resulted in the creation of thousands of datasets, >30 in the retina alone. Analyzing the transcriptomes between different projects is highly desirable because this would allow for better assessment of which biological effects are consistent across independent studies. However it is difficult to compare and contrast data across different projects because there are substantial batch effects from computational processing, single-cell technology utilized, and the natural biological variation. While many single-cell transcriptome-specific batch correction methods purport to remove the technical noise, it is difficult to ascertain which method functions best. Results: We developed a lightweight R package (scPOP, single-cell Pick Optimal Parameters) that brings in batch integration methods and uses a simple heuristic to balance batch merging and cell type/cluster purity. We use this package along with a Snakefile-based workflow system to demonstrate how to optimally merge 766,615 cells from 33 retina datsets and 3 species to create a massive ocular single-cell transcriptome meta-atlas. Conclusions: This provides a model for how to efficiently create meta-atlases for tissues and cells of interest.
Cormatrix® for vessel reconstruction in paediatric cardiac surgery—a word of caution
Authors: Weis Johanna , Geiger Ralf , Kilo Juliane , Zimpfer Daniel
Published: October 2021

OBJECTIVES

The aim of this retrospective study was to determine if Cormatrix® (CM) represents a safe alternative to conventional patch materials used in congenital heart surgery.

METHODS

A total of 57 paediatric patients who underwent cardiac surgery using an Extracellular Matrix Bioscaffold (CM) were categorized into 4 groups according to the patch implant location. Patch-related complications and reintervention rates were analysed. A subgroup of 18 patients was subsequently compared to a matched group of 36 patients who underwent similar surgical procedures with autologous pericardium as patch material.

RESULTS

No patient died during hospitalization. There were 2 late deaths, not related to the implanted CM patch. Fourteen (66.7%) out of 21 patients with arterial patch plasty developed progressive vessel/right ventricular outflow tract stenosis or aneurysm. All 3 patients with a valved CM conduit developed haemodynamically relevant valve stenosis or regurgitation. A total of 18 (31.5%) patients needed reintervention and 12 (21.1%) related to CM. Four (7%) patients needed surgical treatment with operative removal of the stenosis. Redo valve replacement was performed on 2 (3.5%) patients. Six (10.5%) patients required an interventional cardiology procedure at a median interval of 5 months from surgery. The subgroup analysis revealed a significantly lower patch-related reintervention rate in patients treated with autologous pericardium when compared to CM (P = 0.006).

CONCLUSIONS

CM is safe for atrial and ventricular defect closure. The use of CM for arterial vessel reconstruction is associated with higher reintervention rates when compared to autologous pericardium.
Rethinking Proxy War Theory in IR: A Critical Analysis of Principal–Agent Theory
Authors: Farasoo Abbas
Published: October 2021

This paper explores the question of what drives proxy alignment in war and argues that current proxy war scholarship needs further thinking to go beyond focusing on the principal–agent theory and individual actors’ motivation analysis. Rather, there is a need to look at the generative mechanisms of proxy alignment as a process that constitutes patterns of friend–enemy relations. The paper argues securitization patterns from domestic to regional and international levels drive actors to re-evaluate their positions and define their enemies and friends. This is a process of securitization alignment and confluence, which serves as a generative mechanism for proxy alignment in a conflict. Securitization alignment is based on a convergence of securitizations by different actors that create a friend–enemy dynamic and convergence of security interests between actors. The confluence of securitizations from the domestic level to regional and beyond also connects actors across different levels to be in alignment and impact the conflict.
Predelli on Fictional Discourse
Authors: García-Carpintero Manuel
Published: October 2021

John Searle argues that (literary) fictions are constituted by mere pretense—by the simulation of representational activities like assertions, without any further representational aim. They are not the result of sui generis, dedicated speech acts of a specific kind, on a par with assertion. The view had earlier many defenders, and still has some. Stefano Predelli enlists considerations derived from Searle in support of his radical fictionalism. This is the view that a sentence of fictional discourse including a prima facie empty fictional name like “Emma Woodhouse” in fact “is not a sentence, and it encodes no proposition whatsoever.” His argument is broadly abductive; he claims that this view affords compelling explanations of features of fictions he finds well-established, among them that fictions without explicit narrators nonetheless have covert ones. Here I take up his arguments, in defense of the dedicated speech act view. I thus address pressing issues about the status of fictional names and the nature and ubiquity of narrators in fictions.
Surveillance and Molecular Identification ofBorreliaSpecies in Ticks Collected at U.S. Army Garrison Humphreys, Republic of Korea, 2018–2019
Authors: Lee Seung-Ho , Chong Sung-Tae , Kim Heung-Chul , Klein Terry A , Park Kyungmin , Lee Jingyeong , Kim Jeong-Ah , Kim Won-Keun , Song Jin-Won
Published: October 2021

Tick-borne pathogens are contributing factors for the increased incidence of vector-borne diseases throughout the world, including Lyme borreliosis, one of the most prevalent spirochetes belonging to the Borrelia burgdorferi sensu lato group. The present study focused on the detection of Borrelia species from hard ticks collected at U.S. Army Garrison Humphreys, Republic of Korea (ROK), using molecular and genotypic analyses. Tick-borne disease surveillance was conducted from January to December, 2018–2019. A total of 24,281 ticks (2 genera and 5 species) were collected from road-killed Korean Water deer (KWD) and by tick drag. Haemaphysalis longicornis (92.0%) was the most commonly collected species, followed by Haemaphysalis flava (4.9%), Ixodes nipponensis (3.1%), Haemaphysalis phasiana (0.07%), and Haemaphysalis japonica (<0.01%). The ospA gene sequences of Borrelia afzelii were detected in 12/529 pools of I. nipponensis. Three and one pools were positive for B. afzelii and Borrelia miyamotoi, respectively, using the 16s rRNA gene. None of the pools of Haemaphysalis ticks collected from KWD or by tick drag were positive for Borrelia species. I. nipponensis was collected throughout the year from KWD and from February to November by tick drag, suggesting that they were active throughout the year, and expanding the risk period for acquiring Lyme borreliosis and Borrelia relapsing fever in the ROK. This study assessed disease risk factors associated with the prevalence of Lyme disease in ticks collected from KWD and by tick drag using molecular analysis. These results provide an understanding and awareness into the prevalence and molecular characteristics of Borrelia species in the ROK.
INDI—integrated nanobody database for immunoinformatics
Authors: Deszyński Piotr , Młokosiewicz Jakub , Volanakis Adam , Jaszczyszyn Igor , Castellana Natalie , Bonissone Stefano , Ganesan Rajkumar , Krawczyk Konrad
Published: October 2021

Nanobodies, a subclass of antibodies found in camelids, are versatile molecular binding scaffolds composed of a single polypeptide chain. The small size of nanobodies bestows multiple therapeutic advantages (stability, tumor penetration) with the first therapeutic approval in 2018 cementing the clinical viability of this format. Structured data and sequence information of nanobodies will enable the accelerated clinical development of nanobody-based therapeutics. Though the nanobody sequence and structure data are deposited in the public domain at an accelerating pace, the heterogeneity of sources and lack of standardization hampers reliable harvesting of nanobody information. We address this issue by creating the Integrated Database of Nanobodies for Immunoinformatics (INDI, http://naturalantibody.com/nanobodies). INDI collates nanobodies from all the major public outlets of biological sequences: patents, GenBank, next-generation sequencing repositories, structures and scientific publications. We equip INDI with powerful nanobody-specific sequence and text search facilitating access to >11 million nanobody sequences. INDI should facilitate development of novel nanobody-specific computational protocols helping to deliver on the therapeutic promise of this drug format.
Establishment of a near-contiguous genome sequence of the citric acid producing yeast Yarrowia lipolytica DSM 3286 with resolution of rDNA clusters and telomeres
Authors: Luttermann Tobias , Rückert Christian , Wibberg Daniel , Busche Tobias , Schwarzhans Jan-Philipp , Friehs Karl , Kalinowski Jörn
Published: October 2021

Yarrowia lipolytica is an oleaginous yeast that is particularly suitable for the sustainable production of secondary metabolites. The genome of this yeast is characterized by its relatively large size and its high number of different rDNA clusters located in its telomeric regions. However, due to the presence of long repetitive elements in the sub-telomeric regions, rDNA clusters and telomeres are missing in current genome assemblies of Y. lipolytica. Here, we present the near-contiguous genome sequence of the biotechnologically relevant strain DSM 3286. We employed a hybrid assembly strategy combining Illumina and nanopore sequencing reads to integrate all six rDNA clusters as well as telomeric repeats into the genome sequence. By fine-tuning of DNA isolation and library preparation protocols, we were able to create ultra-long reads that not only contained multiples of mitochondrial genomes but also shed light on the inter- and intra-chromosomal diversity of rDNA cluster types. We show that there are ten different rDNA units present in this strain that additionally appear in a predefined order in a cluster. Based on single reads, we also demonstrate that the number of rDNA repeats in a specific cluster varies from cell to cell within a population.
Characterizing batch effects and binding site-specific variability in ChIP-seq data
Authors: Teng Mingxiang , Du Dongliang , Chen Danfeng , Irizarry Rafael A
Published: October 2021

Multiple sources of variability can bias ChIP-seq data toward inferring transcription factor (TF) binding profiles. As ChIP-seq datasets increase in public repositories, it is now possible and necessary to account for complex sources of variability in ChIP-seq data analysis. We find that two types of variability, the batch effects by sequencing laboratories and differences between biological replicates, not associated with changes in condition or state, vary across genomic sites. This implies that observed differences between samples from different conditions or states, such as cell-type, must be assessed statistically, with an understanding of the distribution of obscuring noise. We present a statistical approach that characterizes both differences of interests and these source of variability through the parameters of a mixed effects model. We demonstrate the utility of our approach on a CTCF binding dataset composed of 211 samples representing 90 different cell-types measured across three different laboratories. The results revealed that sites exhibiting large variability were associated with sequence characteristics such as GC-content and low complexity. Finally, we identified TFs associated with high-variance CTCF sites using TF motifs documented in public databases, pointing the possibility of these being false positives if the sources of variability are not properly accounted for.
The role of tender and swollen joints for the assessment of inflammation in PsA using ultrasound
Authors: Bosch Philipp , Lackner Angelika , Dreo Barbara , Husic Rusmir , Ficjan Anja , Gretler Judith , Graninger Winfried , Duftner Christina , Hermann Josef , Dejaco Christian
Published: October 2021

Objective

To evaluate tender joints (TJ) and swollen joints (SJ) for the assessment of ultrasound (US) defined inflammation in PsA.

Methods

Eighty-three PsA patients underwent clinical and US examinations at two scheduled study visits 12 months apart. Tenderness and swelling were assessed at 68 and 66 joints, respectively, and US examinations were conducted at all 68 joints. At patient level, associations with clinical composites and US scores were performed using correlations and by analysing patients with predominantly tender (pTender) or swollen joints (pSwollen). At joint level, a Power Doppler (PD) value ≥ 1 was defined as active synovitis. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months.

Results

SJC showed better correlations with GS/PD scores (r = 0.37/0.47) than with TJC (PD: r = 0.33), while TJC correlated better with patient reported outcomes (PROMs) like patient global assessment (TJC: r = 0.57; SJC r = 0.39). Patients with pTender showed poorer results for PROMs and disease activity scores than patients with pSwollen, but not for laboratory or US markers of inflammation. Swollen joints showed active synovitis in 35% of cases, while only 16% of tender joints were active according to US. Swelling at baseline better predicted active synovitis at the same joint after 12 months [odds ratio (OR) 6.33, P <0.001] as compared with tenderness (OR 3.58, P <0.001).

Conclusions

SJ are more closely linked with US signs of inflammation as compared with TJ in PsA. Joint swelling is a better predictor for signs of US inflammation than tenderness after one year of follow-up.
Structural Racism, Managerialism, and the Future of the Human Services: Rewriting the Rules
Authors: Abramovitz Mimi , Zelnick Jennifer R
Published: October 2021

Over the past several decades, the introduction of the business model, managerialism, into the human services has led to dramatic changes in conditions of work and service delivery. This metric-driven approach increased the emphasis on measured performance outcomes and undercut the mission-driven nature of human services organizations. In 2020, the COVID-19 pandemic and widespread protests against racial injustice exposed routinely ignored structural racism long embedded in our social institutions. This reckoning led social workers to re-examine professional practices, organizational structures, and public policies through a critical, antiracist lens. Applying a racial justice lens to their study of the impact of managerialism in the human services workplace, authors identified troubling evidence of systemic racism in leadership hierarchies, worker control/surveillance on the job, quality of the physical work environment, exposure to workplace violence, exclusion by microinequities, and agency commitment to social justice. Worker resistance, ethical dilemmas, and well-being also varied by race. To become an antiracist profession, social work must seek long-term change in the human services workplace. The following analysis of the combined negative impact of managerialism and structural racism on human services organizations names the problem and presses us to rewrite the rules so we become a racial justice profession.
Expression of N-Terminal-Deficient E-Cadherin Protein in Invasive Lobular Carcinoma of the Breast
Authors: Yasui Haruna , Kawata Takuya , Muramatsu Koji , Kakuda Yuko , Oishi Takuma , Norose Tomoko , Notsu Akifumi , Nishimura Seiichiro , Fukuoka Junya , Sugino Takashi
Published: October 2021

Invasive lobular carcinoma (ILC) of the breast is characterized by the discohesive growth of tumor cells, which is mainly associated with the complete loss of E-cadherin (E-cad) expression. However, some aberrant expression patterns of E-cad protein that are inconsistent with their morphologies have been reported in ILC. We report herein ILC cases expressing a new type of abnormal E-cad protein that lacks the N-terminal domain, but conserves the C-terminal domain on the cell membrane. Immunohistochemical staining of 299 ILC cases using specific antibodies against the N-terminal or C-terminal region of E-cad revealed that 227 (76%) cases showed loss of the membranous expression of both terminuses (N−/C−) and 72 (24%) cases showed expression of only the C-terminus (N−/C+). In all cases, the expression of p120-catenin and β-catenin coincided with the expression of the C-terminus of E-cad. Clinicopathologic analysis revealed that N−/C+ expression in ILC cells was significantly associated with the histologic subtype (especially mixed-type ILC with another histologic type) and immunohistochemical molecular subtype (especially the triple-negative subtype), but not with prognostic factors (pT or pN). In addition, 12 of 15 cases (80%) with aberrant cytoplasmic localization of the N-terminal of E-cad showed diffuse membranous expression of the C-terminal domain. Additional immunohistochemistry using an antibody recognizing the extracellular juxtamembrane region showed that 28 (39%) of the N−/C+ cases had lost membranous expression, suggesting diversity in the deletion pattern of the N-terminal region. Our findings provide a novel mechanism for the loss of E-cad function because of N-terminal-deficient E-cad protein in ILC.
Non-18F-FDG-Avid Intrahepatic Metastasis of Breast Cancer Revealed by 68Ga-FAPI PET/CT
Authors: Wang Qixin , Tang Wenxin , Cai Liang , Chen Yue
Published: October 2021

A patient with intrahepatic breast cancer metastasis underwent both 18F-FDG and 68Ga-FAPI PET/CT. However, the lesions are only 68Ga-FAPI avid. Our case illustrates that 68Ga-FAPI PET/CT can be more sensitive in detecting intrahepatic metastasis of breast cancer in some cases.
Incidental [18F]PSMA-1007 Appendiceal Uptake Mimicking Nodal Disease
Authors: Nawwar Ayah Adel , Searle Julie , Lyburn Iain Douglas
Published: October 2021

When interpreting an [18F]prostate specific membrane antigen (PSMA)–1007 PET/CT, it is important to understand the normal biodistribution of the tracer. A 73-year-old man with prostate cancer underwent [18F]PSMA-1007 PET/CT for biochemical recurrence. There was no abnormal uptake in the prostatectomy bed, but PSMA-avid pelvic nodal disease was found. Incidental intense focal uptake was also noted corresponding to the tip of the appendix, which was concluded to be physiological. This is an example of an uncommon site of physiological uptake of [18F]PSMA-1007 in the appendix.
Renal Infarction Imaged With [18F]Prostate-Specific Membrane Antigen–1007 PET/CT
Authors: Ahmadi Bidakhvidi Niloefar , Van Craenenbroeck Amaryllis H. , Oyen Raymond , Van Laere Koen , Goffin Karolien
Published: October 2021

A 61-year-old post–renal transplant man developed pain in the region of the allograft 4 days after transplantation. Contrast-enhanced CT scan revealed multiple small perfusion defects in the renal graft cortex. Multifocal renal cortical infarction was suspected. A [99mTc]Tc-DMSA SPECT/CT showed several small regions with decreased uptake. In addition, an [18F]PSMA-1007 PET/CT confirmed these uptake defects and revealed additional defects. The renal cortical infarctions presumably originated from intraoperative emboli emerging from the arterial anastomosis. Treatment with acetylsalicylic acid 100 mg led to favorable evolution of the renal function biochemically. Follow-up DMSA scintigraphy 3 months later showed resolution of the renal cortical defects.
Unusual Metastases of Esophageal Squamous Cell Carcinoma
Authors: Chen Yi-Hsun , Lin Chia-Yang , Chen Yi-Ting , Wu I-Chen , Wang Yao-Kuang
Published: October 2021

Colonic or peritoneal metastasis from esophageal squamous cell carcinoma is extremely rare. We present the case of a 68-year-old man with esophageal squamous cell carcinoma who received concurrent chemoradiation therapy. The follow-up whole-body 18F-FDG PET/CT was performed 6 months after initial chemotherapy and showed new lesions of increased FDG activity in the colon as well as peritoneum. The final pathological diagnosis proved these metastases were from esophageal squamous cell carcinoma.
Pulmonary Sarcomatoid Carcinoma With Epiglottis and Ileum Metastasis Detected by 18F-FDG PET/CT
Authors: Gao Cailiang , Zou Qiao , Liu Huiting
Published: October 2021

Pulmonary sarcomatoid carcinoma is a rare subtype of non–small cell lung cancer with poor prognosis. It often metastasizes to lymph nodes, bone, adrenal gland, liver, and brain. Herein, we present a case of a pulmonary sarcomatoid carcinoma patient with epiglottis and ileum metastasis detected by 18F-FDG PET/CT. Lymphoma or multiple primary cancers with or without regional node metastasis were suspected. Ultimately, histopathology after biopsy revealed pulmonary sarcomatoid carcinoma with epiglottic and ileum metastases. Our case highlights the unique advantages of 18F-FDG PET/CT in searching for the unsuspected metastasis.
An Atypical Case of Meckel's Diverticulum Assessed by SPECT/CT Imaging
Authors: Mittl Gregory S. , Servaes Sabah-e-Noor , Zhuang Hongming
Published: October 2021

A 17-year-old adolescent boy presented with multiple episodes of hematochezia. After a negative 99mTcO4 scan, upper endoscopy, colonoscopy, and CT angiography, the patient underwent a second 99mTcO4 scan with ranitidine. The anterior images demonstrated a faint, delayed focus of uptake in the midabdomen without correlate on lateral projections. SPECT/CT was performed for localization with the focus of activity seen in an anterior loop of distal small bowel adjacent to the umbilicus. The patient subsequently underwent diagnostic laparoscopy and resection of the diverticulum with postoperative resolution of the symptoms.
68Ga-FAPI PET/CT Distinguishes the Reactive Lymph Nodes From Tumor Metastatic Lymph Nodes in a Patient With Nasopharyngeal Carcinoma
Authors: Shang Qihang , Zhao Long , Pang Yizhen , Yu Yifeng , Chen Haojun
Published: October 2021

Accurate clinical staging is crucial for managing nasopharyngeal carcinoma (NPC). However, false-positive finding of cervical lymph nodes in 18F-FDG PET/CT and MRI may lead to unnecessary chemotherapy for NPC. In this case, we report a patient with NPC who was incorrectly diagnosed with bilateral cervical lymph node metastases by both 18F-FDG PET/CT and MRI. Subsequent pathology results showed proliferating lymphoid cells with no signs of tumor metastasis. Interestingly, no abnormal 68Ga-FAPI uptake was observed in the nonmetastatic reactive lymph nodes. Therefore, 68Ga-FAPI PET/CT may be useful for assessment of pretreatment lymph node status in NPC.
Mangrovicoccus algicola sp. nov., an alginate lyase – producing marine bacterium
Authors: Shi Lei , Mo Kunlian , Bao Shixiang , Wu Qingjuan , Xue Chunmei , Huang Huiqin
Published: October 2021

A Gram-stain-negative, non-motile, ellipsoid bacterium, designated HB182678T, was isolated from brown alga collected from Hainan province, PR China. Growth was observed at 10–50 °C (optimum 37–40 °C), at pH 6–10 (optimum pH 8) and in the presence of 0.5–13% (w/v) NaCl (optimum, 2–4%). The predominant isoprenoid quinone was Q-10 and the major fatty acids were C18 : 1 ω7c, C16 : 0, C18 : 0 and C19 : 0 cyclo ω8c. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, an unidentified phospholipid, two unidentified glycolipids and three unidentified aminophospholipids. The size of the draft genome was 4.40 Mbp with G+C content 68.8 mol%. Phylogenetic analysis of 16S rRNA gene sequence indicated that strain HB182678T belonged to the genus

Mangrovicoccus

, and the closest phylogenetically related species was

Mangrovicoccus ximenensis

T1lg56T (with the similarity of 96.3%). Whole genome average nucleotide identity (ANI) value between them was 84.3% and in silico DNA–DNA hybridization value was 27.2%. The combined phylogenetic relatedness, phenotypic and genotypic features supported the conclusion that strain HB182678T represents a novel species of the genus

Mangrovicoccus

, for which the name Mangrovicoccus algicola sp. nov. is proposed. The type strain is HB182678T (=MCCC 1K04624T=KCTC 82318T).
Acetobacter garciniae sp. nov., an acetic acid bacterium isolated from fermented mangosteen peel in Thailand
Authors: Yukphan Pattaraporn , Charoenyingcharoen Piyanat , Kingcha Yutthana , Likhitrattanapisal Somsak , Muangham Supattra , Tanasupawat Somboon , Yamada Yuzo
Published: October 2021

Two isolates, MS16-SU-2Tand MS18-SU-3, obtained from fermented mangosteen peel in vinegar were suggested to constitute a new species assignable to the genusAcetobacterbased on the results of 16S rRNA gene sequencing. The two isolates showed the highest sequence similarity (98.58%) toAcetobacter tropicalisNBRC 16470TandAcetobacter senegalensisLMG 23690T. However, the calculated similarity values were lower than the threshold for species demarcation. The phylogenetic analysis showed that the branches of the two isolates were separated from otherAcetobacterspecies, and the two isolates constituted a new species in the genusAcetobacter. The genomic DNA of isolate MS16-SU-2Twas sequenced. The assembled genome of the isolate was analysed, and the results showed that the highest average nucleotide identity value of 75.9 % was withAcetobacter papayaeJCM 25143Tand the highest digital DNA–DNA hybridization value of 25.1 % was withAcetobacter fallaxLMG 1636T, which were lower than the cutoff values for species delineation. The phylogenetic tree based on the genome sequences showed that the lineage of isolate MS16-SU-2Twas most closely related toA. papayaeJCM 25143TandAcetobacter suratthaniensisTBRC 1719T, but separated from the branches of these two species. In addition, the two isolates could be distinguished from the type strains of closely related species by their phenotypic characteristics and MALDI-TOF profiles. Therefore, the two isolates, MS16-SU-2T(=TBRC 12339T=LMG 32243T) and MS18-SU-3 (=TBRC 12305), can be assigned to an independent species within the genusAcetobacter, and the name ofAcetobacter garciniaesp. nov. is proposed for the two isolates.
HERC5 E3 ligase mediates ISGylation of hepatitis B virus X protein to promote viral replication
Authors: Bawono Rheza Gandi , Abe Takayuki , Qu Mengting , Kuroki Daisuke , Deng Lin , Matsui Chieko , Ryo Akihide , Suzuki Tetsuro , Matsuura Yoshiharu , Sugiyama Masaya , Mizokami Masashi , Shimotohno Kunitada , Shoji Ikuo
Published: October 2021

Ubiquitin and ubiquitin-like protein modification play important roles in modulating the functions of viral proteins in many viruses. Here we demonstrate that hepatitis B virus (HBV) X protein (HBx) is modified by ISG15, which is a type I IFN-inducible, ubiquitin-like protein; this modification is called ISGylation. Immunoblot analyses revealed that HBx proteins derived from four different HBV genotypes accepted ISGylation in cultured cells. Site-directed mutagenesis revealed that three lysine residues (K91, K95 and K140) on the HBx protein, which are well conserved among all the HBV genotypes, are involved in acceptance of ISGylation. Using expression plasmids encoding three known E3 ligases involved in the ISGylation to different substrates, we found that HERC5 functions as an E3 ligase for HBx-ISGylation. Treatment with type I and type III IFNs resulted in the limited suppression of HBV replication in Hep38.7-Tet cells. When cells were treated with IFN-α, silencing of ISG15 resulted in a marked reduction of HBV replication in Hep38.7-Tet cells, suggesting a role of ISG15 in the resistance to IFN-α. In contrast, the silencing of USP18 (an ISG15 de-conjugating enzyme) increased the HBV replication in Hep38.7-Tet cells. Taken together, these results suggest that the HERC5-mediated ISGylation of HBx protein confers pro-viral functions on HBV replication and participates in the resistance to IFN-α-mediated antiviral activity.
Agile design and development of a high throughput cobas® SARS-CoV-2 RT-PCR diagnostic test
Authors: Manohar Chitra , Sun Jingtao , Schlag Peter , Santini Chris , Fontecha Marcel , Lötscher Pirmin , Bier Carolin , Goepfert Kristina , Duncan Dana , Spier Gene , Jarem Daniel , Kosarikov Dmitriy
Published: October 2021

Diagnostic testing is essential for management of the COVID-19 pandemic. An agile assay design methodology, optimized for the cobas® 6800/8800 system, was used to develop a dual-target, qualitative SARS-CoV-2 RT-PCR test using commercially available reagents and existing sample processing and thermocycling profiles. The limit of detection was 0.004 to 0.007 TCID50/mL for USA-WA1/2020. Assay sensitivity was confirmed for SARS-CoV-2 variants Alpha, Beta, Gamma, Delta and Kappa. The coefficients of variation of the cycle threshold number (Ct) were between 1.1 and 2.2%. There was no difference in Ct using nasopharyngeal compared to oropharyngeal swabs in universal transport medium (UTM). A small increase in Ct was observed with specimens collected in cobas® PCR medium compared to UTM. In silico analysis indicated that the dual-target test is capable of detecting all >1,800,000 SARS-CoV-2 sequences in the GISAID database. Our agile assay design approach facilitated rapid development and deployment of this SARS-CoV-2 RT-PCR test.
Simulation and predictions of a new COVID-19 pandemic wave in Ukraine with the use of generalized SIR model
Authors: Nesteruk Igor
Published: October 2021

A new wave of the COVID-19 pandemic in Ukraine, which began in the summer of 2021, was characterized by almost exponential growth of smoothed daily numbers of new cases. This is a matter of great concern and the need to immediately predict the dynamics of the epidemic in order to assess the possible maximum values of new cases, the risk of infection and the number of deaths. The generalized SIR-model and corresponding parameter identification procedure was used to simulate and predict the dynamics of this epidemic wave. The new COVID-19 epidemic wave in Ukraine will begin to subside in mid-October 2021, but its duration will be quite long. Unfortunately, new cases may appear by the summer of 2022.
Wild cereal grain consumption among Early Holocene foragers of the Balkans predates the arrival of agriculture
Authors: Cristiani E. , Radini A. , Zupancich A. , Gismondi A. , D’Agostino A. , Ottoni C. , Carra M. , Vukojičić S. , Constantinescu M. , Antonović D. , Price T. Douglas , Borić D.
Published: October 2021

Forager focus on wild cereal plants has been documented in the core zone of domestication in southwestern Asia, while evidence for forager use of wild grass grains remains sporadic elsewhere. In this paper, we present starch grain and phytolith analyses of dental calculus from 61 Mesolithic and Early Neolithic individuals from five sites in the Danube Gorges of the central Balkans. This zone was inhabited by likely complex Holocene foragers for several millennia before the appearance of the first farmers ∼6200 cal BC. We also analyzed forager ground stone tools for evidence of plant processing. Our results based on the study of dental calculus show that certain species of Poaceae (species of the genus Aegilops) were used since the Early Mesolithic, while ground stone tools exhibit traces of a developed grass grain processing technology. The adoption of domesticated plants in this region after ∼6500 cal BC might have been eased by the existing familiarity with wild cereals.
Vaccine effectiveness of Ad26.COV2.S against symptomatic COVID-19 and clinical outcomes in Brazil: a test-negative study design
Authors: Ranzani Otavio T , dos Santos Leite Rogério , Castilho Larissa Domingues , Maymone Gonçalves Crhistinne Cavalheiro , Resende Geraldo , de Melo Rosana Leite , Croda Julio
Published: October 2021

We used a test-negative design to estimate the vaccine effectiveness of Ad26.COV2.S (Janssen) against symptomatic COVID-19 and clinical outcomes in Mato-Grosso do Sul, Brazil. We analyzed 11,817 RT-PCR tests. The mean age was 37 (SD=17) years, 2,308 (20%) of individuals more or equal than 50 years and almost two-thirds of the population was Brown/Pardo. Adjusted effectiveness against symptomatic COVID-19 after 28 days of the single dose was 50.9% (95% CI, 35.5-63.0). Adjusted effectiveness against clinical outcomes was 72.9% (95% CI, 35.1-91.1) for hospitalization, 92.5% (95% CI, 54.9-99.6) for ICU admission, 88.7% (95% CI, 17.9-99.5) for mechanical ventilation and 90.5% (95% CI, 31.5-99.6) for death. Despite lacking precision on some estimates, a single dose of Ad26.COV2.S vaccine continues to protect specially for severe forms of COVID-19 in the context of new variants.
Loss of wings induces the expression of the worker-like phenotype in queens of a ponerine ant
Authors: Pyenson Benjamin , Albin-Brooks Christopher , Burhyte Corinne , Liebig Jürgen
Published: October 2021

Many highly-eusocial insect species are characterized by morphological differences between females. This is especially pronounced in ants where queens usually possess a fully developed thorax with wings and are specialized for reproduction while workers have a reduced thorax without wings and show various levels of reproductive degeneration that is associated with their helper role in the colony. Despite their morphological differentiation, queens and workers still show some plasticity leading to overlapping behavioral and physiological phenotypes. We investigated the level of queen plasticity and the factor that induces a worker-like phenotype in the ant speciesHarpegnathos saltatorthat has limited queen-worker dimorphism and workers that can assume the reproductive role of a queen in the colony. By comparing alate and dealate young queens, so-called gynes, we found that the loss of wings initiated the expression of behavioral and physiological characteristics of ant workers. In contrast to alate gynes, dealate gynes displayed higher frequencies of worker-like behaviors. In addition, dealate gynes showed a worker-like range of reproductive states unlike alate gynes. Like workers, dealate gynes lost the chemical signaling that is characteristic of alate gynes. Since gynes can activate this worker-like phenotype after wing loss, the essential difference between the ant queens and workers in this species with limited queen-worker dimorphism is a dispersal polyphenism. If the phenotypic plasticity observed inH. saltatoris representative of the early stages of ant eusociality, an emerging dispersal dimorphism rather than a distinct reproductive dimorphism might represent one of the first steps in ant evolution.

Summary Statement

Ant queens who have lost their wings express worker-like behaviors and physiology including the display of dominance behavior during hierarchy establishment, which is normally a worker-only behavior in this species.
Genetics of the human microglia regulome refines Alzheimer’s disease risk loci
Authors: Kosoy Roman , Fullard John F. , Zeng Biao , Bendl Jaroslav , Dong Pengfei , Rahman Samir , Kleopoulos Steven P. , Shao Zhiping , Humphrey Jack , Lopes Katia de Paiva , Charney Alexander W. , Kopell Brian. H. , Raj Towfique , Bennett David , Kellner Christopher P. , Haroutunian Vahram , Hoffman Gabriel E. , Roussos Panos
Published: October 2021

Microglia are brain resident myeloid cells that play a critical role in neuroimmunity and the etiology of Alzheimer’s Disease (AD). Yet our understanding of how the genetic regulatory landscape controls microglial function and contributes to disease is limited. Here, we performed transcriptome and chromatin accessibility profiling in primary human microglia from 150 donors to identify genetically-driven variation and cell-specific enhancer-promoter interactions. Integrative fine-mapping analysis identified putative regulatory mechanisms for 21 AD risk loci, of which 18 were refined to a single gene, including 3 novel genes (KCNN4, FIBP and LRRC25). Transcription factor regulatory networks captured AD risk variation and identified SPI1 as a key regulator of microglia expression and AD risk. This comprehensive resource capturing variation in the human microglia regulome provides novel insights into the etiology of neurodegenerative disease.

One-Sentence Summary

Characterizing the genetic regulation of chromatin accessibility and gene expression in human microglia refines molecular mechanisms of Alzheimer’s disease risk loci.
The genome of the camphor tree and the genetic and climatic relevance of the top-geoherbalism in this medicinal plant
Authors: Jiang Rihong , Chen Xinlian , Liao Xuezhu , Peng Dan , Han Xiaoxu , Zhu Changsan , Wang Ping , Hufnagel David E. , Li Cheng , Li Kaixiang , Wang Li
Published: October 2021

Camphor tree (Cinnamomum camphora (L.) J. Presl), a species in the magnoliid family Lauraceae, is known for its rich volatile oils and is used as a medical cardiotonic and as a scent in many perfumed hygiene products. Here, we present a high-quality chromosome-scale genome of C. camphora with a scaffold N50 of 64.34 Mb and an assembled genome size of 755.41 Mb. Phylogenetic inference revealed that the magnoliids are a sister group to the clade of eudicots and monocots. Comparative genomic analyses identified two rounds of ancient whole-genome duplication (WGD). Tandem duplicated genes exhibited a higher evolutionary rate, a more recent evolutionary history and a more clustered distribution on chromosomes, contributing to the production of secondary metabolites, especially monoterpenes and sesquiterpenes, which are the principal essential oil components. Three-dimensional analyses of the volatile metabolites, gene expression and climate data of samples with the same genotype grown in different locations showed that low temperature and low precipitation during the cold season modulate the expression of genes in the terpenoid biosynthesis pathways, especially TPS genes, which facilitates the accumulation of volatile compounds. Our study lays a theoretical foundation for policy-making regarding the agroforestry applications of camphor tree.
Tuberin levels during cellular differentiation in brain development
Authors: Khatir Bashaer Abu , Davis Gordon Omar , Sameem Mariam , Patel Rutu , Fong Jackie , Lubanska Dorota , da Silva Elizabeth Fidalgo , Porter Lisa A.
Published: October 2021

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

HIGHLIGHTS

Tuberin protein levels are decreased in the Purkinje cell layer in later stages of embryonic development.

Tuberin protein and mRNA levels decrease as cells undergo neuronal differentiation.

Downregulation of Tuberin impairs neurosphere formation.

Tuberin is implicated in the maintenance of stemness in the developing brain.
Trace-element XAFS sensitivity: a stress test for a new XRF multi-detector
Authors: Carlomagno Ilaria , Antonelli Matias , Aquilanti Giuliana , Bellutti Pierluigi , Bertuccio Giuseppe , Borghi Giacomo , Cautero Giuseppe , Cirrincione Daniela , de Giudici Giovanni , Ficorella Francesco , Gandola Massimo , Giuressi Dario , Medas Daniela , Mele Filippo , Menk Ralf H. , Olivi Luca , Orzan Giulio , Picciotto Antonino , Podda Francesca , Rachevski Alexandre , Rashevskaya Irina , Stebel Luigi , Vacchi Andrea , Zampa Gianluigi , Zampa Nicola , Zorzi Nicola , Meneghini Carlo
Published: October 2021

X-ray absorption fine-structure (XAFS) spectroscopy can assess the chemical speciation of the elements providing their coordination and oxidation state, information generally hidden to other techniques. In the case of trace elements, achieving a good quality XAFS signal poses several challenges, as it requires high photon flux, counting statistics and detector linearity. Here, a new multi-element X-ray fluorescence detector is presented, specifically designed to probe the chemical speciation of trace 3d elements down to the p.p.m. range. The potentialities of the detector are presented through a case study: the speciation of ultra-diluted elements (Fe, Mn and Cr) in geological rocks from a calcareous formation related to the dispersal processes from Ontong (Java) volcanism (mid-Cretaceous). Trace-elements speciation is crucial in evaluating the impact of geogenic and anthropogenic harmful metals on the environment, and to evaluate the risks to human health and ecosystems. These results show that the new detector is suitable for collecting spectra of 3d elements in trace amounts in a calcareous matrix. The data quality is high enough that quantitative data analysis could be performed to determine their chemical speciation.
Temperature-compensated constitutive model of fused filament fabrication 3D printed PLA materials with full extrusion temperatures
Authors: Zhu Kaiyang , Deng Zichen , Dai Shi , Yu Yajun
Published: October 2021

Purpose

This study aims to focus on the effect of interlayer bonding and thermal decomposition on the mechanical properties of fused filament fabrication-printed polylactic acid specimens at high extrusion temperatures.

Design/methodology/approach

A printing process, that is simultaneous manufacturing of contour and specimen, is used to improve the printing accuracy at high extrusion temperatures. The effects of the extrusion temperature on the mechanical properties of the interlayer and intra-layer are evaluated via tensile experiments. In addition, the microstructure evolution affected by the extrusion temperature is observed using scanning electron microscopy.

Findings

The results show that the extrusion temperature can effectively improve the interlayer bonding property; however, the mechanical properties of the specimen for extrusion temperatures higher than 270°C may worsen owing to the thermal decomposition of the polylactic acid (PLA) material. The optimum extrusion temperature of PLA material in the three-dimensional (3D) printing process is recommended to be 250–270°C.

Originality/value

A temperature-compensated constitutive model for 3D printed PLA material under different extrusion temperatures is proposed. The present work facilitates the prediction of the mechanical properties of specimens at an extrusion temperature for different printing temperatures and different layers.
Green coffee polyphenols in formulations of functional yoghurt and their quality attributes
Authors: Pimpley Vaibhavi A , Maity Supriya , Murthy Pushpa S
Published: October 2021

Antioxidant‐enriched probiotic yoghurt was developed using spray‐dried green coffee extract (SGC). A full factorial design was employed to optimise the spray‐drying conditions. A significant yield of polyphenols besides the physico‐chemical properties was attained in SGC. Green coffee‐enriched yoghurt (GY) containing 0.5% SGC resulted with desirable pH (4.7), acidity, colour and minimum syneresis. The chemical composition of GY depicted low calorific value, and significant antioxidant activity corresponding to polyphenols and alkaloids. The GY depicted improved flavour, texture and other sensory attributes with a shelf life of 14 days at 4 °C. GY is a promising functional food.
Consensus statement on measures to promote equitable authorship in the publication of research from international partnerships
Authors: Morton B. , Vercueil A. , Masekela R. , Heinz E. , Reimer L. , Saleh S. , Kalinga C. , Seekles M. , Biccard B. , Chakaya J. , Abimbola S. , Obasi A. , Oriyo N.
Published: October 2021

Despite the acknowledged injustice and widespread existence of parachute research studies conducted in low‐ or middle‐income countries by researchers from institutions in high‐income countries, there is currently no pragmatic guidance for how academic journals should evaluate manuscript submissions and challenge this practice. We assembled a multidisciplinary group of editors and researchers with expertise in international health research to develop this consensus statement. We reviewed relevant existing literature and held three workshops to present research data and holistically discuss the concept of equitable authorship and the role of academic journals in the context of international health research partnerships. We subsequently developed statements to guide prospective authors and journal editors as to how they should address this issue. We recommend that for manuscripts that report research conducted in low‐ or middle‐income countries by collaborations including partners from one or more high‐income countries, authors should submit accompanying structured reflexivity statements. We provide specific questions that these statements should address and suggest that journals should transparently publish reflexivity statements with accepted manuscripts. We also provide guidance to journal editors about how they should assess the structured statements when making decisions on whether to accept or reject submitted manuscripts. We urge journals across disciplines to adopt these recommendations to accelerate the changes needed to halt the practice of parachute research.
The strange occurrence of male cannibalism on adult females in snakes
Authors: Glaudas Xavier , Fuento Nicolas
Published: October 2021

Cannibalism is widespread in the animal kingdom. The most common, well‐known cases are found in some arthropod systems where the larger females occasionally consume the smaller males before, during, or after mating (i.e., sexual cannibalism). The killing and consumption of females by males are, on the other hand, seemingly much rarer and theoretically more difficult to explain, at least among adults, because the consumption of females would result in the loss of potential mates for males. Here, we use observations submitted to a community science reporting system to describe three instances of adult males feeding on adult females in the Montpellier snake, Malpolon monspessulanus, in the south of France. We discuss our observations in the theoretical framework of cannibalism to provide potential explanations for these observations and briefly review empirical findings of cannibalism in vertebrates, which confirms that this sex‐reversed form of sexual cannibalism is rare in nature.