bluuebunny/crossref_metadata_2025 huggingface dataset:
OSHA Workplace Violence Enforcement
Authors: Arbury Sheila , Collins Natasha R. , Magtahas Janette , Holmes Mikki , Hodgson Michael J.
Published: January 2022

Objective:

To examine violence inspections at the Occupational Safety and Health Administration (OSHA).

Methods:

The authors examined all inspections that involved violence against workers begun by January 1, 2019. They conducted semi-structured interviews with compliance officers who had conducted inspections on a sample of facilities that received General Duty Clause (GDC) citations (n = 22) or Hazard Alert Letters (HALs) (n = 22).

Results:

By January 1, 2019, OSHA initiated 726 “violence” inspections, with 502 (69.1%) in healthcare. In healthcare, 45 (11.1%) resulted in GDC citations and 241 (67.7%) in HALs. GDC facilities received statistically significantly lower scores in 5 of 6 domains examined through semi-structured interviews than HAL facilities. Both groups of facilities had poorly designed recordkeeping systems.

Conclusions:

Health care facilities continue to generate worker complaints with poorly designed violence prevention programs.
Occupational Exposure to Trichloramine and Endotoxins
Authors: Westerlund Jessica , Phil Lic , Bryngelsson Ing-Liss , Fornander Louise , Löfstedt Håkan , Graff Pål
Published: January 2022

Objective:

To study occupational exposure totrichloramine and endotoxins in air at adventure and rehabilitation swimming pool facilities from an adverse health effects perspective.

Methods:

Air concentrations of trichloramine and endotoxins were measured in five adventure and 10 rehabilitation facilities. Respiratory and ocular symptoms were self-reported, and spirometry and fraction of exhaled nitric oxide (FE

no

) were measured.

Results:

Compared to rehabilitation facilities, the mean trichloramine concentrations in the adventure facilities were higher, both personal (80 μg/m3 (n 
= 41) vs 19 μg/m3 (n = 21)) and stationary (183 μg/m3 (n = 51) vs 23 μg/m3 (n = 32)), with higher frequency of ocular and respiratory symptoms. Low stationary endotoxin levels (<0.64 to 25 EU/m3) were found, compared to the reference value (90 EU/m3).

Conclusions:

Higher trichloramine concentrations in air and more ocular and respiratory symptoms in adventure facilities call for adequate occupational exposure limits.
Cervical Intraepithelial Neoplasia 3 (Cervical Intraepithelial Neoplasia 3/High-Grade Squamous Intraepithelial Lesion) in Human Papillomavirus–Vaccinated Women—Results From a Tertiary Referral Center
Authors: Domröse Christian Markus , Wieland Ulrike , Pilch Henryk , Einzmann Thomas , Schömig-Markiefka Birgid , Mallmann Peter , Silling Steffi , Mallmann Michael Rudolf
Published: January 2022

Objective

High-grade cervical intraepithelial neoplasia (CIN 3) still develops in some vaccinated women despite established effectiveness of prophylactic human papillomavirus (HPV) vaccination. The purpose of this study was to define characteristics of women with CIN 3 after HPV vaccination referred to a gynecological dysplasia unit.

Materials and Methods

Retrospective analysis of HPV-vaccinated women with CIN 3 in a single German center. Between July 2018 and September 2020, 791 women were referred to our university hospital–based dysplasia unit for colposcopic evaluation of abnormal cytological findings. Human papillomavirus vaccination status was retrieved. Human papillomavirus typing was performed in lesional biopsies and cervical swabs.

Results

Nine women were identified who had previously been vaccinated with the quadrivalent HPV vaccine (Q-HPV) and were diagnosed with histologically confirmed CIN 3/high-grade squamous intraepithelial lesion. The Q-HPV had been administered between 12 and 28 years of age and 1–13 years before CIN 3 diagnosis. Nine different high-risk (HR)-HPV types were found in the CIN 3 biopsies, 6 monoinfections (twice HPV 16, once HPV 18, HPV 31, HPV 52, HPV 58, respectively) and 3 dual infections (HPV 33 + 52, HPV 51 + 52, HPV 53 + 66). Seven of these 9 HR-HPV types are not covered by Q-HPV, but only 2 CIN 3 lesions carried HR-HPV types not included in the nonavalent HPV vaccine.

Conclusions

It is important to implement vaccination recommendations and administer HPV vaccination as early as possible in HPV-naive individuals. Because not all HR-HPV types are covered by the available HPV vaccines, other types may still cause CIN 3/high-grade squamous intraepithelial lesion. This requires further screening after vaccination, especially in women who were previously vaccinated with the bivalent or the quadrivalent HPV vaccine.
Hospital Charges Associated With Critical Bronchiolitis From 2009 to 2019*
Authors: Slain Katherine N. , Malay Sindhoosha , Shein Steven L.
Published: January 2022

OBJECTIVES:

To evaluate the contribution of PICU care to increasing hospital charges for patients with bronchiolitis over a 10-year study period.

DESIGN:

In this retrospective multicenter study, changes in annual hospital charges (adjusted for inflation) were analyzed using linear regression for subjects admitted to the PICU with invasive mechanical ventilation (PICU + IMV) and without IMV (PICU – IMV), and for children not requiring PICU care.

SETTING:

Free-standing children’s hospitals contributing to the Pediatric Health Information System (PHIS) database.

SUBJECTS:

Children less than 2 years with bronchiolitis discharged from a PHIS hospital between July 2009 and June 2019. Subjects were categorized as high risk if they were born prematurely or had a chronic complex condition.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

PICU patients were 26.5% of the 283,006 included subjects but accrued 66% of the total $14.83 billion in charges. Annual charges increased from $1.01 billion in 2009–2010 to $2.07 billion in 2018–2019, and PICU patients accounted for 83% of this increase. PICU + IMV patients were 22% of all PICU patients and accrued 64% of all PICU charges, but PICU – IMV patients without a high-risk condition had the highest relative increase in annual charges, increasing from $76.7 million in 2009–2010 to $377.9 million in 2018–2019 (374% increase, ptrend < 0.001).

CONCLUSIONS:

In a multicenter cohort study of children hospitalized with bronchiolitis, PICU patients, especially low-risk children without the need for IMV, were the highest driver of increased hospital charges over a 10-year study period.
A novel pivot ankle/foot prosthesis reduces sound side loading and risk for osteoarthritis: a pragmatic randomized controlled trial
Authors: Runciman Phoebe , Cockcroft John , Derman Wayne
Published: January 2022

Background:

Individuals with unilateral transtibial amputation are at risk of abnormal mechanical joint loading and development of osteoarthritis on sound side joint structures.

Objectives:

This study describes the spatiotemporal and kinetic and kinematic parameters related to osteoarthritis in participants while using (A) a solid-ankle cushioned-heel prosthesis (SACH), (B) a conventional energy storage and return (ESAR) foot prosthesis, and (C) a novel ESAR (N-ESAR) foot prosthesis.

Study design:

A pragmatic randomized controlled trial.

Methods:

K3–K4 ambulators used three feet in a 2-week randomized cross-over order. Kinetics of vertical ground reaction forces (vGRFs) and 3D kinematics of joint angles were integrated to provide normalized parameters. Data were analyzed using one way and mixed model Analysis of variance (ANOVAs) (p < 0.05) and Cohen d statistic.

Results:

Twenty participants, aged 40 ± 16 years with body mass index of 24.7 ± 3.6 kg/m2, experienced minimal change in the spatiotemporal parameters between feet. Participants using the N-ESAR foot prosthesis experienced reduced peak knee external adduction moment (p = 0.030), peak vGRFs (p < 0.001), and peak loading rate of vGRFs (p = 0.030). Peak knee flexion moments only changed when using the solid-ankle cushioned-heel prosthesis, in a positive direction (p = 0.014). Using the N-ESAR prosthesis also increased peak distal shank power during late stance phase (p < 0.001).

Conclusions:

A novel ankle/foot ESAR prosthesis reduces loading on the sound side. With extended use of the N-ESAR foot prosthesis, these findings may provide the prosthesis user with improved outcomes related to sound side loading and development of osteoarthritis.
Primary Breast Lymphoma Detected by 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT
Authors: Tao Yi , Wang Feifei , Chen Liming , Huang Zhanwen
Published: January 2022

Primary breast lymphoma is a rare form of extranodal lymphoma. We report 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT findings of breast lymphoma in a 60-year-old woman. Both breast ultrasound and mammogram showed a mass in the right breast and suggested that the mass might be a malignant tumor. She was referred for an 18F-FDG PET/CT scan and subsequently recruited in our 68Ga-DOTA-FAPI-04 PET/CT trial. Both scans revealed the breast mass with intense tracer uptake. Biopsy and immunohistochemical examinations of the mass confirmed the diagnosis of diffuse large B-cell lymphoma.
68Ga-DOTATATE and 68Ga-PSMA Uptake in Granulomatous Prostatitis
Authors: Ruan Dan , Sun Long
Published: January 2022

68Ga-PSMA and 68Ga-DOTATATE PET/CT have shown promising performance in diagnosing prostate cancer and neuroendocrine tumors, but there are also pitfalls. We report a case of a 78-year-old man with prostate lesions showing intense uptake of 18FDG, 68Ga-PSMA, and 68Ga-DOTATATE simultaneously, with heterogeneous enhancement on contrast-enhanced CT and abnormal signal changes on PET/MRI. It was finally diagnosed as granulomatous prostatitis. This case suggests that granulomatous prostatitis has a high uptake of various imaging agents and is easily misdiagnosed as prostate cancer.
Incidental Finding of Moderna COVID-19 Vaccination–Related Axillary Lymphadenopathy on 201Tl Myocardial Perfusion Imaging
Authors: Chan Hung-Pin , Shen Daniel Hueng-Yuan , Yang Ming-Hui , Hu Chin , Tyan Yu-Chang
Published: January 2022

We presented here a 71-year-old man with a history of thyroid cancer post total thyroidectomy and 131I ablation and right renal cell carcinoma post right partial nephrectomy. He reported persistent chest tightness and pain after the first dose of the Moderna COVID-19 (mRNA-1273) vaccine. Thus, coronary heart disease was suspected, and the patient was referred for MPI (myocardial perfusion imaging). Focal 201Tl uptake in the left axillary region was found incidentally on MPI, and SPECT/CT revealed enlarged benign-looking lymph nodes. The diagnostic is in favor of reactive hyperplasia after the intramuscular injection of vaccine into left deltoid muscle.
68Ga-PSMA-11 PET Identified Tumor Recurrence in Prostatectomy Bed With Rising PSA of 0.9 ng/mL but Negative on MRI and 18F-Fluciclovine PET Scan
Authors: Xu Guofan , Lu Yang
Published: January 2022

A 63-year-old man with prostate cancer was treated with prostatectomy who had postoperative PSA of 0.6 ng/mL. A pelvic MRI, whole body bone scan, CT chest and abdomen exams did not show any residual or metastatic prostate disease. His PSA increased to 0.9 ng/mL in two months. A fluciclovine PET did not show any tracer avid metastatic or recurrent disease. A 0.7 cm non-fluciclovine-avid nodule at the left prostatectomy bed was considered benign. A 68Ga-PSMA-11 PET one month later showed avid radiotracer uptake within this nodule. The patient received androgen deprivation treatment after PSMA PET/CT and responded well.
18F-PSMA-11 PET/MRI in Prostate Adenocarcinoma With Mucinous Features
Authors: Zhao Qian , Yang Bo , Dong Aisheng , Zuo Changjing
Published: January 2022

Primary mucinous tumors involving the prostate gland are rare. We describe MRI and 18F-PSMA-11 PET/MRI findings in a case of prostate adenocarcinoma with mucinous features. The prostate tumor showed inhomogeneous hyperintensity on T2-weighted images due to high extracellular mucin content and inhomogeneous 18F-PSMA-11 uptake with SUVmax of 12.5. This case indicates PSMA PET imaging may be helpful for detection of this uncommon variant of prostate adenocarcinoma.
Lesion-Based Radiomics Signature in Pretherapy 18F-FDG PET Predicts Treatment Response to Ibrutinib in Lymphoma
Authors: Jimenez Jorge E. , Dai Dong , Xu Guofan , Zhao Ruiyang , Li Tengfei , Pan Tinsu , Wang Linghua , Lin Yingyan , Wang Zhangyang , Jaffray David , Hazle John D. , Macapinlac Homer A. , Wu Jia , Lu Yang
Published: January 2022

Purpose

The aim of this study was to develop a pretherapy PET/CT-based prediction model for treatment response to ibrutinib in lymphoma patients.

Patients and Methods

One hundred sixty-nine lymphoma patients with 2441 lesions were studied retrospectively. All eligible lymphomas on pretherapy 18F-FDG PET images were contoured and segmented for radiomic analysis. Lesion- and patient-based responsiveness to ibrutinib was determined retrospectively using the Lugano classification. PET radiomic features were extracted. A radiomic model was built to predict ibrutinib response. The prognostic significance of the radiomic model was evaluated independently in a test cohort and compared with conventional PET metrics: SUVmax, metabolic tumor volume, and total lesion glycolysis.

Results

The radiomic model had an area under the receiver operating characteristic curve (ROC AUC) of 0.860 (sensitivity, 92.9%, specificity, 81.4%; P < 0.001) for predicting response to ibrutinib, outperforming the SUVmax (ROC AUC, 0.519; P = 0.823), metabolic tumor volume (ROC AUC, 0.579; P = 0.412), total lesion glycolysis (ROC AUC, 0.576; P = 0.199), and a composite model built using all 3 (ROC AUC, 0.562; P = 0.046). The radiomic model increased the probability of accurately predicting ibrutinib-responsive lesions from 84.8% (pretest) to 96.5% (posttest). At the patient level, the model's performance (ROC AUC = 0.811; P = 0.007) was superior to that of conventional PET metrics. Furthermore, the radiomic model showed robustness when validated in treatment subgroups: first (ROC AUC, 0.916; P < 0.001) versus second or greater (ROC AUC, 0.842; P < 0.001) line of defense and single treatment (ROC AUC, 0.931; P < 0.001) versus multiple treatments (ROC AUC, 0.824; P < 0.001).

Conclusions

We developed and validated a pretherapy PET-based radiomic model to predict response to treatment with ibrutinib in a diverse cohort of lymphoma patients.
Complications of Percutaneous Kidney Allograft Biopsy: Systematic Review and Meta-analysis
Authors: Ho Quan Yao , Lim Cynthia Ciwei , Tan Hui Zhuan , Sultana Rehena , Kee Terence , Htay Htay
Published: January 2022

Background.

Kidney biopsy is important to guide the management of allograft dysfunction but has a risk of complications. This review aimed to determine the incidence and risk factors of complications after kidney allograft biopsy.

Methods.

This is a systematic review and meta-analysis of randomized controlled trials, cohort studies, or case-control studies indexed on PubMed, Embase, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry, and ClinicalTrials.gov, limited to the English language, from January 2000 to December 2020, including adult and pediatric kidney allograft biopsies. Primary outcomes were gross hematuria, bleeding requiring transfusion, and major complications (requiring interventions such as blood transfusion or surgical or radiological interventions).

Results.

The review included 72 studies (40 082 biopsies). The quality of included studies was suboptimal. Pooled rates of gross hematuria, bleeding requiring transfusion, and major complications were 3.18% [95% confidence interval (95% CI), 2.31-4.19], 0.31% (95% CI, 0.15-0.52) and 0.89% (95% CI, 0.61-1.22), respectively. Gross hematuria rates were lower in high-income compared with middle-income countries (2.59% versus 6.44%, P < 0.01) and biopsies performed by radiology as compared with nephrology departments (1.25% versus 3.71%, P < 0.01). Blood transfusion rates were lower in pediatrics than adults (0.0% versus 0.65%, P < 0.01). Major complications were lower in biopsies performed by specialists as compared with trainees (0.02% versus 3.64%, P < 0.01). Graft loss and mortality were extremely rare. Limitations included missing data, few randomized controlled trials, and possible publication bias.

Conclusions.

The risk of complications after kidney allograft biopsy was low. Given the low quality of included studies, risk factors for complications should be further examined in future studies.
Visually induced dizziness
Authors: Steenerson Kristen K. , Hoskin Justin , Fife Terry D.
Published: January 2022

Purpose of review

Visually induced dizziness (VID) is a common phenomenon in vestibular disorders of both peripheral and central causes. This article provides a review of the most updated understandings of definition, pathophysiology, and treatment options.

Recent findings

The pathophysiology is complex and its severity or persistence may be related both to the underlying cause and heritable factors. Environmental and psychological factors may influence the degree of impact of VID on daily life function. Treatment is mostly empiric at this point but includes pharmacologic, desensitization, cognitive behavioral therapies, visual rehabilitation, and treatment of the underlying cause whenever present. Additional research is needed to clarify the best management of this vestibular symptom as well as some of the other conditions with which it is commonly associated.

VID is a fairly common vestibular syndrome constitutng spatial disorientation without illusory motion. As it is seen in both peripheral and central vestibular disorders, it should be considered a syndrome or constellation of symptoms rather than a discrete disorder. In some cases, it may be the presenting symptom with no other clear disorder linked to it.
Should I stay or should I go? How activity synchronization affects fission decisions
Authors: Busia Laura , Schaffner Colleen M. , Aureli Filippo
Published: January 2022

Group-living animals need to deal with conflicting interests to maintain cohesion. When the costs of doing so outweigh the benefits, the group may (temporarily) split into two or more subgroups. Conflicting interests can concern what activity to pursue or the direction of travel. Temporary group separation is a common feature in species with a high degree of fission–fusion dynamics. We investigated the role activity synchronization played in fission decisions in a spider monkey group living in the Otoch Ma'ax Yetel Kooh Nature Reserve, Yucatan, Mexico. For 21 months, we recorded every fission event occurring in the followed subgroup, as well as the subgroup activity. We classified the activity as ‘synchronized’ when at least 75% of subgroup members performed the same activity (resting, foraging, socializing or travelling); otherwise, we classified it as ‘non-synchronized’. We found that fission events occurred more often when the activity was non-synchronized. In addition, when the activity was synchronized, fission events occurred more often when spider monkeys were travelling than when they were engaged in other subgroup activities. Our findings highlight the role of conflicting interests over the activity to pursue and travel direction in fission decisions.
Double nicking by RNA-directed Cascade-nCas3 for high-efficiency large-scale genome engineering
Authors: Hao Yile , Wang Qinhua , Li Jie , Yang Shihui , Zheng Yanli , Peng Wenfang
Published: January 2022

New CRISPR-based genome editing technologies are developed to continually drive advances in life sciences, which, however, are predominantly derived from systems of Type II CRISPR-Cas9 and Type V CRISPR-Cas12a for eukaryotes. Here we report a novel CRISPR-n(nickase)Cas3 genome editing tool established upon a Type I-F system. We demonstrate that nCas3 variants can be created by alanine-substituting any catalytic residue of the Cas3 helicase domain. While nCas3 overproduction via plasmid shows severe cytotoxicity, an
in situ
nCas3 introduces targeted double-strand breaks, facilitating genome editing without visible cell killing. By harnessing this CRISPR-nCas3
in situ
gene insertion, nucleotide substitution and deletion of genes or genomic DNA stretches can be consistently accomplished with near-100% efficiencies, including simultaneous removal of two large genomic fragments. Our work describes the first establishment of a CRISPR-nCas3-based genome editing technology, thereby offering a simple, yet useful approach to convert the naturally most abundantly occurring Type I systems into advanced genome editing tools to facilitate high-throughput prokaryotic engineering.
Physico-chemical and spectroscopic investigation of flavonoid dispersed C

n

TAB micelles
Authors: Kumar Dileep , Sachin K. M. , Kumari Naveen , Bhattarai Ajaya
Published: January 2022

In this study, kaempferol (0.2 m/mmol kg
−1
) dispersed cationic surfactant micelles were prepared as a function of alkyltrimethylammonium bromide (C

n

TAB) hydrophobicity (C = 12 to C = 16). The dispersion study of kaempferol in different C

n

TAB, i.e. dodecyltrimethylammonium bromide (C = 12), tetradecyltrimethylammonium bromide (C = 14) and hexadecyltrimethylammonium bromide (C = 16), was conducted with the physico-chemical properties of density, sound velocity, viscosity, surface tension, isentropic compressibility, acoustic impedance, surface excess concentration and area occupied per molecule and thermodynamic parameters Gibbs free energy, enthalpy and activation energy measured at 298.15 K. These properties were measured with varying concentration of C

n

TAB from 0.0260 to 0.0305 mol kg
−1
in a 10% (w/w) aqueous dimethyl sulfoxide solvent system. The variations in these measured properties have been used to infer the kaempferol dispersion stability via hydrophobic–hydrophilic, hydrophilic–hydrophilic, van der Waals, hydrogen bonding and other non-covalent interactions.
Moisture- and mould-proof characteristics of surface modified wood for musical instrument soundboards
Authors: Xu Caiping , Liu Zhenbo , Li Xingyun , Li Wanli
Published: January 2022

Wood is the main material used for musical instrument soundboard fabrication, for practical and cultural reasons. As a natural material, however, wood is easily degraded due to moisture or fungal corrosion. Most traditional wood protection methods were devised for structural materials, and may thus not be suitable for application in musical instrument soundboard materials. In the current study, a novel nanomaterial-based modification method was applied to wood. The surface of wood was coated with polyurethane and MgAl-layered double hydroxide nanosheets after a convenient impregnation process. The modified wood exhibited improved hydrophobicity and mould-resistance, while maintaining its acoustic properties. This modified wood may facilitate the construction of soundboards with longer lifespans.
Theoretical insights into the antiradical activity and copper-catalysed oxidative damage of mexidol in the physiological environment
Authors: Hoa Nguyen Thi , Van Bay Mai , Mechler Adam , Vo Quan V.
Published: January 2022

Mexidol (
MD
, 2-ethyl-6-methyl-3-hydroxypyridine) is a registered therapeutic agent for the treatment of anxiety disorders. The chemical structure suggests that
MD
may also act as an antioxidant. In this study, the hydroperoxyl radical scavenging activity of
MD
was studied to establish baseline antioxidant activity, followed by an investigation of the effect of
MD
on the copper-catalysed oxidative damage in biological systems, using computational methods. It was found that
MD
exhibits moderate radical scavenging activity against HOO
•
in water and pentyl ethanoate solvents following the single electron transfer and formal hydrogen transfer mechanisms, respectively.
MD
can chelate Cu(II), forming complexes that are much harder to reduce than free Cu(II):
MD
chelation completely quenches the Cu(II) reduction by ascorbic acid and suppresses the rate of reduction reaction by

O

2

⋅
−

that are the main reductants of Cu(II) in biological environments. Therefore,
MD
exerts its anti-HO
•
activity primarily as an OIL-1 inhibitor.
Static and dynamic formant scaling conveys body size and aggression
Authors: Anikin Andrey , Pisanski Katarzyna , Reby David
Published: January 2022

When producing intimidating aggressive vocalizations, humans and other animals often extend their vocal tracts to lower their voice resonance frequencies (formants) and thus sound big. Is acoustic size exaggeration more effective when the vocal tract is extended before, or during, the vocalization, and how do listeners interpret within-call changes in apparent vocal tract length? We compared perceptual effects of static and dynamic formant scaling in aggressive human speech and nonverbal vocalizations. Acoustic manipulations corresponded to elongating or shortening the vocal tract either around (Experiment 1) or from (Experiment 2) its resting position. Gradual formant scaling that preserved average frequencies conveyed the impression of smaller size and greater aggression, regardless of the direction of change. Vocal tract shortening from the original length conveyed smaller size and less aggression, whereas vocal tract elongation conveyed larger size and more aggression, and these effects were stronger for static than for dynamic scaling. Listeners familiarized with the speaker's natural voice were less often ‘fooled’ by formant manipulations when judging speaker size, but paid more attention to formants when judging aggressive intent. Thus, within-call vocal tract scaling conveys emotion, but a better way to sound large and intimidating is to keep the vocal tract consistently extended.
Morphological characters in light of new molecular phylogenies: the caudal-fin skeleton of Ovalentaria
Authors: Thieme Philipp , Schnell Nalani K. , Parkinson Kerryn , Moritz Timo
Published: January 2022

The Ovalentaria is a taxon of teleosts that has been proposed based on molecular analyses only. Previously widely separated families are assembled in this taxon. For the first time, the Ovalentaria are analysed using a comparative morphological approach. The caudal-fin skeleton of 355 species covering all 48 ovalentarian families are examined in cleared and stained specimens, µCT datasets and X-ray images as well as from the literature. A total of 38 morphological characters are evaluated and used for ancestral character state reconstructions and phylogenetic analyses. Results provide hypotheses for a scenario of the evolution of the caudal-fin skeleton and its ground plan in Ovalentaria. An evolutionary trend towards the reduction of skeletal elements in the caudal fin is observed. Connections between the evolution of the caudal-fin skeleton and modes of locomotion found in ovalentarian taxa are discussed. Phylogenetic analyses based on the caudal-fin morphology provide topologies for intra-ovalentarian relationships that largely agree with molecular hypotheses.
The crystal structure of vaccinia virus protein E2 and perspectives on the prediction of novel viral protein folds
Authors: Gao William N. D. , Gao Chen , Deane Janet E. , Carpentier David C. J. , Smith Geoffrey L. , Graham Stephen C.
Published: January 2022

The morphogenesis of vaccinia virus (VACV, family Poxviridae), the smallpox vaccine, is a complex process involving multiple distinct cellular membranes and resulting in multiple different forms of infectious virion. Efficient release of enveloped virions, which promote systemic spread of infection within hosts, requires the VACV protein E2 but the molecular basis of E2 function remains unclear and E2 lacks sequence homology to any well-characterised family of proteins. We solved the crystal structure of VACV E2 to 2.3 Å resolution, revealing that it comprises two domains with novel folds: an N-terminal annular (ring) domain and a C-terminal globular (head) domain. The C-terminal head domain displays weak structural homology with cellular (pseudo)kinases but lacks conserved surface residues or kinase features, suggesting that it is not enzymatically active, and possesses a large surface basic patch that might interact with phosphoinositide lipid headgroups. Recent deep learning methods have revolutionised our ability to predict the three-dimensional structures of proteins from primary sequence alone. VACV E2 is an exemplar ‘difficult’ viral protein target for structure prediction, being comprised of multiple novel domains and lacking sequence homologues outside Poxviridae. AlphaFold2 nonetheless succeeds in predicting the structures of the head and ring domains with high and moderate accuracy, respectively, allowing accurate inference of multiple structural properties. The advent of highly accurate virus structure prediction marks a step-change in structural virology and beckons a new era of structurally-informed molecular virology.
A possible mechanism of farnesol tolerance in C. albicans biofilms implemented by activating the PKC signalling pathway and stabilizing ROS levels
Authors: Chen Shengyan , Xu Zheng , Liu Siqi , Duan Wei , Huang Yun , Wei Xin
Published: January 2022

Introduction. Biofilms are the natural growth state for most microorganisms. C. albicans biofilms are composed of multiple cell types (round budding yeast-form cells, oval pseudohyphal cells, and elongated hyphal cells) encased in an extracellular matrix. C. albicans biofilms are notorious for resistance to antimicrobial treatments, a property that might be determined by complex mechanisms. Exogenous farnesol exerts a certain antifungal activity against C. albicans with medical implications. Different from other microbes, C. albicans biofilms can tolerate exogenous farnesol at high concentration with some cells still surviving and even maintaining proliferation, but the mechanism is unclear.

Hypothesis. The study hypothesizes that C. albicans resists farnesol by activating the PKC signalling pathway.

Aim. The study aims to discuss the molecular mechanism of C. albicans resistance to farnesol.

Methodology. The ROS levels, the genes and proteins of the PKC pathway were compared between the farnesol-tolerant and non-tolerant groups using ROS levels assay, q-RT PCR and Western blot, respectively. Further, the mutant strains (pkc1Δ/Δ and mkc1Δ/Δ) were constructed, then the survival rates and ROS levels of biofilms exposed to farnesol were compared between mutant and wild strains. The morphological changes were observed using TEM.

Results. The survival rates of C. albicans biofilms decreased rapidly under the lower concentration of farnesol (P<0.05), and kept stable (P>0.05) as the concentration rose up to 200 µM. The gene expression of the PKC pathway increased, while ROS levels remained stable and even decreased in the farnesol-tolerant biofilms, compared with those in the farnesol-nontolerant biofilms after farnesol treatment (P<0.05); pkc1 and mkc1 were significantly upregulated by C. albicans during the development of biofilm tolerance to farnesol. The cell wall and cytoplasm of pkc1Δ/Δ and mkc1Δ/Δ were damaged, and the ROS level increased (P<0.05); meanwhile, the survival rate of biofilms decreased compared with that of wild-type strain under the same farnesol concentrations (P<0.05). ROS inhibitors reversed these changes in pkc1Δ/Δ and mkc1Δ/Δ when the mutant strains exposed to farnesol.

Conclusion.
C. albicans biofilms can tolerate high concentrations of farnesol by activating pkc1 and mkc1 of the PKC pathway and stabilizing ROS levels. The pkc1 and mkc1 are two key genes regulated by C. albicans in the process of biofilm tolerance to farnesol.
Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
Authors: Hatoum Alexander S , Colbert Sarah M.C. , Johnson Emma C , Huggett Spencer B. , Deak Joseph D. , Pathak Gita A , Jennings Mariela V. , Paul Sarah E , Karcher Nicole R. , Hansen Isabella , Baranger David A.A. , Edwards Alexis , Grotzinger Andrew David ,   Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Tucker-Drob Elliot M , Kranzler Henry , Davis Lea K , Sanchez-Roige Sandra , Polimanti Renato , Gelernter Joel , Edenberg Howard J. , Bogdan Ryan , Agrawal Arpana
Published: January 2022

Genetic liability to substance use disorders can be parsed into loci conferring general and substance-specific addiction risk. We report a multivariate genome-wide association study that disaggregates general and substance-specific loci for problematic alcohol use, problematic tobacco use, and cannabis and opioid use disorders in a sample of 1,025,550 individuals of European and 92,630 individuals of African descent. Nineteen loci were genome-wide significant for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries PDE4B was significant (among others), suggesting dopamine regulation as a cross-trait vulnerability. The addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions, and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis, 1 for opioids) included metabolic and receptor genes. These findings provide insight into the genetic architecture of general and substance-specific use disorder risk that may be leveraged as treatment targets.
Investigation of the Effects of N-Linked Glycans on the Stability of the Spike Protein in SARS-CoV-2 by Molecular Dynamics Simulations
Authors: Tekin E.Deniz
Published: January 2022

We perform all-atom molecular dynamics simulations to study the effects of the N-linked glycans on the stability of the spike glycoprotein in SARS-CoV-2. After a 100 ns of simulation on the spike proteins without and with the N-linked glycans, we found that the presence of glycans increases the local stability in their vicinity; even though their effect on the full structure is negligible.

Graphical Abstract
Practical and Thermodynamic Constraints on Electromicrobially-Accelerated CO2 Mineralization
Authors: Marecos Sabrina , Brigham Rae , Dressel Anastacia , Gaul Larissa , Li Linda , Satish Krishnathreya , Tjokorda Indira , Zheng Jian , Schmitz Alexa M. , Barstow Buz
Published: January 2022

By the end of the century tens of gigatonnes of CO2 will need to be removed from the atmosphere every year to maintain global temperatures. Natural weathering of ultramafic rocks and subsequent mineralization reactions can convert atmospheric CO2 into ultra-stable carbonates. But, while natural weathering will eventually draw down all excess CO2, this process will need hundreds of thousands of years to do it. The CO2 mineralization process could be accelerated by weathering ultramafic rocks with biodegradable lixiviants like organic acids. But, in this article we show that if these lixiviants are produced from cellulosic biomass, the demand created by CO2 mineralization could monopolize the world’s supply of biomass even if CO2 mineralization performance is high. In this article we demonstrate that electromicrobial production technologies (EMP) that combine renewable electricity and microbial metabolism could produce lixiviants for as little as $200 to $400 per tonne at solar electricity prices achievable within the decade. Furthermore, this allows the lixiviants needed to sequester a tonne of CO2 to be produced for less than $100, even with modest CO2 mineralization performance.
Optimization of capture protocols across species targeting up to 32000 genes and their extension to pooled DNA
Authors: Mariac Cédric , Bethune Kévin , de Aquino Sinara Oliveira , Abdelrahman Mohamed , Barnaud Adeline , Billot Claire , Zekraoui Leila , Couderc Marie , Kané Ndjido , Andrade Alan Carvalho , Marraccini Pierre , Kiwuka Catherine , Albar Laurence , Sabot François , Poncet Valérie , Couvreur Thomas LP , Berthouly-Salazar Cécile , Vigouroux Yves
Published: January 2022

Premise

In-solution based capture is becoming a method of choice for sequencing targeted sequence.

Methods and results

We assessed and optimized a capture protocol in 20 different species from 6 different plant genus using kits from 20,000 to 200,000 baits targeting from 300 to 32,000 genes. We evaluated both the effectiveness of the capture protocol and the fold enrichment in targeted sequences. We proposed a protocol with multiplexing up to 96 samples in a single hybridization and showed it was an efficient and cost-effective strategy. We also extended the use of capture to pools of 100 samples and proved the efficiency of the method to assess allele frequency. Using a set of various organisms with different genome sizes, we demonstrated a correlation between the percentage of on-target reads vs. the relative size of the targeted sequences.

Conclusion

Altogether, we proposed methods, strategies, cost-efficient protocols and statistics to better evaluate and more effectively use hybridization capture.
The megabase-scale crossover landscape is independent of sequence divergence
Authors: Lian Qichao , Solier Victor , Walkemeier Birgit , Huettel Bruno , Schneeberger Korbinian , Mercier Raphael
Published: January 2022

Meiotic recombination frequency varies along chromosomes and strongly correlates with sequence divergence. However, the causality underlying this correlation is unclear. To untangle the relationship between recombination landscapes and polymorphisms, we characterized the genome-wide recombination landscape in the absence of polymorphisms, usingArabidopsis thalianahomozygous inbred lines in which a few hundred genetic markers were introduced through mutagenesis. We found that megabase-scale recombination landscapes in inbred lines are strikingly similar to the recombination landscapes in hybrids, with the sole exception of heterozygous large rearrangements where recombination is prevented locally. In addition, we found that the megabase-scale recombination landscape can be accurately predicted by chromatin features. Our results show that polymorphisms are not causal for the shape of the megabase-scale recombination landscape, rather, favor alternative models in which recombination and chromatin shape sequence divergence across the genome.
Single-Nucleus Chromatin Accessibility Identifies a Critical Role for TWIST1 in Idiopathic Pulmonary Fibrosis Myofibroblast Activity
Authors: Valenzi Eleanor , Bahudhanapati Harinath , Tan Jiangning , Tabib Tracy , Sullivan Daniel I. , Sembrat John , Fan Li , Chen Kong , Rojas Mauricio , Lafargue Audrey , Felsher Dean W. , Tran Phuoc T. , Kass Daniel J. , Lafyatis Robert
Published: January 2022

In idiopathic pulmonary fibrosis (IPF) myofibroblasts are key effectors of fibrosis and architectural distortion by excessive deposition of extracellular matrix and their acquired contractile capacity. Single-cell RNA-sequencing has precisely defined the IPF myofibroblast transcriptome, but identifying critical transcription factor activity by this approach is imprecise. We performed and integrated snATAC-seq and scRNA-seq from human IPF and donor control explants to identify differentially accessible chromatin regions and enriched transcription factor motifs within lung cell populations. TWIST1 and other E-box transcription factor motifs were significantly enriched in IPF myofibroblasts compared to both IPF non-myogenic and control fibroblasts. TWIST1 expression was also selectively upregulated in IPF myofibroblasts. Overexpression of Twist1 in lung COL1A2-expressing fibroblasts in bleomycin-injured mice was associated with increased collagen synthesis. Our studies utilizing human multiomic single-cell analyses combined with in vivo murine disease models confirm a critical regulatory function for TWIST1 in IPF myofibroblast activity in the fibrotic lung. Understanding the global process of opening TWIST1 and other E-box TF motifs that govern myofibroblast differentiation may identify new therapeutic interventions for fibrotic pulmonary diseases.
Evaluation of methods incorporating biological function and GWAS summary statistics to accelerate discovery
Authors: Moore Amy , Marks Jesse , Quach Bryan C. , Guo Yuelong , Bierut Laura J. , Gaddis Nathan C. , Hancock Dana B. , Page Grier P. , Johnson Eric O.
Published: January 2022

Where sufficiently large genome-wide association study (GWAS) samples are not currently available or feasible, methods that leverage increasing knowledge of the biological function of variants may illuminate discoveries without increasing sample size. We comprehensively evaluated 18 functional weighting methods for identifying novel associations. We assessed the performance of these methods using published results from multiple GWAS waves across each of five complex traits. Although no method achieved both high sensitivity and positive predictive value (PPV) for any trait, a subset of methods utilizing pleiotropy and expression quantitative trait loci nominated variants with high PPV (>75%) for multiple traits. Application of functionally weighting methods to enhance GWAS power for locus discovery is unlikely to circumvent the need for larger sample sizes in truly underpowered GWAS, but these results suggest that applying functional weighting to GWAS can accurately nominate additional novel loci from available samples for follow-up studies.
Bioinformatics Analysis of the Potentially Functional circRNA-miRNA-mRNA Network in Breast Cancer
Authors: Erdoğan Cihat , Suer İlknur , Kaya Murat , Kurt Zeyneb , Öztürk Şükrü , Aydın Nizamettin
Published: January 2022

Objective

Breast cancer (BC) is a heterogeneous type of cancer that occurs as a result of distinct molecular alterations in breast tissue. Although there are many new developments in treatment and targeted therapy for BC in recent years, this cancer type is still the most common one among women with high morbidity and mortality. Therefore, new research is still needed for biomarker detection.

Methods

GSE101124 and GSE182471 datasets were obtained from Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (circRNAs). The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases were used to identify the significantly dysregulated microRNAs (miRNAs) and genes considering the Prediction Analysis of Microarray (PAM50) classification. The circRNA-miRNA-gene relationship was investigated using the Cancer Specific CircRNA (v2.0) (CSCD), miRDB, miRWalk and miRTarBase databases. The circRNA–miRNA–mRNA regulatory network was constructed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation. The protein-protein interaction network was constructed by the STRING 2021 database and visualized by the Cytoscape tool (v3.9.0). Then, raw miRNA data and genes were filtered using some selection criteria according to a specific expression level in PAM50 subgroups. A bottleneck method was utilized to obtain highly interacted hub genes using cytoHubba Cytoscape plugin. The overall survival (OS) and disease-free survival (DFS) analysis were performed for these hub genes, which are detected within the miRNA and circRNA axis in our study.

Results

We identified three circRNAs, three miRNAs, and eighteen candidate target genes that may play an important role in BC. In addition, it has been determined that these molecules can be useful in the classification of BC, especially in determining the basal-like breast cancer (BLBC) subtype.

Conclusions

We conclude that hsa_circ_0000515/ miR-486-5p/ SDC1 axis may be an important biomarker candidate in distinguishing patients in the BLBC group, especially according to the PAM50 classification of BC.
A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection
Authors: Vazquez-Rodriguez Augusto , Shaqour Bahaa , Guarch-Pérez Clara , Choińska Emilia , Riool Martijn , Verleije Bart , Beyers Koen , Costantini Vivian J.A. , Święszkowski Wojciech , Zaat Sebastian A. J. , Cos Paul , Felici Antonio , Ferrari Livia
Published: January 2022

Biomaterial-associated infections are a major healthcare challenge as they are responsible for high disease burden in critically ill patients. In this study, we have developed drug-eluting antibacterial catheters to prevent catheter-related infections. Niclosamide (NIC), originally a well-studied antiparasitic drug, was incorporated into the polymeric matrix of thermoplastic polyurethane (TPU) via solvent casting, and catheters were fabricated using hot-melt extrusion technology. The mechanical and physicochemical properties of TPU polymers loaded with NIC were studied. NIC was released in a sustained manner from the catheters and exhibited antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis in different in vitro models. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection mouse model using a methicillin-susceptible and methicillin-resistant strain of S. aureus. The released NIC from the produced catheters reduced bacterial colonization of the catheter as well as of the surrounding tissue. A sustained in vivo release of NIC from the catheters for at least 14 days was observed. In summary, the NIC-releasing hot-melt extruded catheters prevented implant colonization and reduced the bacterial colonization of peri-catheter tissue by methicillin sensitive as well as resistant S. aureus in a biomaterial-associated infection mouse model and has good prospects for preclinical development.
FunOrder 2.0 – a fully automated method for the identification of co-evolved genes
Authors: Vignolle Gabriel A. , Mach Robert L. , Mach-Aigner Astrid R. , Derntl Christian
Published: January 2022

Coevolution is an important biological process that shapes interacting species or even proteins – may it be physically interacting proteins or consecutive enzymes in a metabolic pathway. The detection of co-evolved proteins will contribute to a better understanding of biological systems. Previously, we developed a semi-automated method, termed FunOrder, for the detection of co-evolved genes from an input gene or protein set. We demonstrated the usability and applicability of FunOrder by identifying essential genes in biosynthetic gene clusters from different ascomycetes. A major drawback of this original method was the need for a manual assessment, which may create a user bias and prevents a high-throughput application. Here we present a fully automated version of this method termed FunOrder 2.0. To fully automatize the method, we used several mathematical indices to determine the optimal number of clusters in the FunOrder output, and a subsequent k-means clustering based on the first three principal components of a principal component analysis of the FunOrder output. Further, we replaced the BLAST with the DIAMOND tool, which enhanced speed and allows the future integration of larger proteome databases. The introduced changes slightly decreased the sensitivity of this method, which is outweighed by enhanced overall speed and specificity. Additionally, the changes lay the foundation for future high-throughput applications of FunOrder 2.0 in different phyla to solve different biological problems.

AUTHOR SUMMARY

Coevolution is a process which arises between different species or even different proteins that interact with each other. Any change occurring in one partner must be met by a corresponding change in the other partner to maintain the interaction throughout evolution. These interactions may occur in symbiotic relationships or between rivaling species. Within an organism, consecutive enzymes of metabolic pathways are also subjected to coevolution. We developed a fully automated method, FunOrder 2.0, for the detection of co-evolved proteins, which will contribute to a better understanding of protein interactions within an organism. We demonstrate that this method can be used to identify essential genes of the secondary metabolism of fungi, but FunOrder 2.0 may also be used to detect pathogenicity factors or remains of horizontal gene transfer next to many other biological systems that were shaped by coevolution.