bluuebunny/crossref_metadata_2025 huggingface dataset:
Hamsters Protected from SARS-CoV-2 Delta Variant Challenge after Two Doses of Adjuvanted SARS-CoV-2 Recombinant Spike Protein (S-2P) and One Dose of Beta S-2P
Authors: Kuo Tsun-Yung , Lien Chia En , Lin Yi-Jiun , Lin Meei-Yun , Wu Chung-Chin , Tang Wei-Hsuan , Campbell John D , Traquina Paula , Chuang Ya-Shan , Liu Luke Tzu-Chi , Cheng Jinyi , Chen Charles
Published: April 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern negatively impact the effectiveness of vaccines. In this study, we challenge hamsters with the delta variant after 2- or 3-dose inoculations with SARS-CoV-2 vaccines constructed from stabilized prefusion spike proteins (S-2P) of Wuhan (W) and beta (B) variants. Compared to 3 doses of W S-2P, 2 doses of W S-2P followed by a third dose of B S-2P induced the highest neutralizing antibody titer against live SARS-CoV-2 virus and enhanced neutralization of omicron variant pseudovirus. Reduced lung live virus titer and pathology suggested that all vaccination regimens protect hamsters from SARS-CoV-2 delta variant challenge.
Serial Homology and Segment Identity in the Arthropod Head
Authors: Lev Oren , Edgecombe Gregory D , Chipman Ariel D
Published: April 2022

Synopsis

The anterior-most unit of the crown-group arthropod body plan includes three segments, the pre-gnathal segments, that contain three neuromeres that together comprise the brain. Recent work on the development of this anterior region has shown that its three units exhibit many developmental differences to the more posterior segments, to the extent that they should not be considered serial homologs. Building on this revised understanding of the development of the pre-gnathal segments, we suggest a novel scenario for arthropod head evolution. We posit an expansion of an ancestral single-segmented head at the transition from Radiodonta to Deuteropoda in the arthropod stem group. The expanded head subdivided into three segmental units, each maintaining some of the structures of the ancestral head. This scenario is consistent with what we know of head evolution from the fossil record and helps reconcile some of the debates about early arthropod evolution.
Effectiveness and safety of colistin among older adults: a systematic review and meta-analysis
Authors: Margalit Ili , Prendki Virginie , Tishler Ori , Falcone Marco , Tiseo Giusy , Leibovici-Weissman Yaara , Paul Mical , Yahav Dafna ,   ESCMID Study Group for Infections in the Elderly (ESGIE)
Published: April 2022

Objectives

Limited data are available to guide colistin use in older adults (>65 years old). We aimed to assess the effectiveness and safety of colistin in this population.

Methods

Systematic review and meta-analysis of original data from randomized control trials, cohort studies and case–control studies assessing colistin regimens with various comparisons for any infection. Original data were obtained from corresponding authors of original studies. The primary outcome was all-cause 1 month mortality; secondary outcomes included clinical and microbiological outcomes and adverse events, including acute kidney injury. Two independent reviewers screened citations, extracted data and assessed risk of bias. ORs with 95% CIs were pooled.

Results

We included 38 publications (41 comparisons) reporting 2857 elderly individuals: 29 studies compared a colistin-based regimen versus another regimen (comparison 1) and 10 compared colistin monotherapy versus colistin combination (comparison 2). No significant difference in 1 month mortality was demonstrated between colistin and comparator (comparison 1, OR 1.13, 95% CI 0.80–1.60; comparison 2, OR 0.99, 95% CI 0.78–1.27). Clinical failure was significantly more likely with colistin-based therapy versus comparator (OR 1.52, 95% CI 1.13–2.06). Acute kidney injury was also significantly more common with colistin-based combinations versus other drugs (OR 3.81, 95% CI 2.14–6.77).

Conclusions

For older adults, colistin-based therapy resulted in no mortality difference, compared with other regimens, for any infection. Clinical failure and acute kidney injury were significantly more common with colistin-based regimens. Close renal function monitoring is needed while using colistin in older adults.
Consumer workarounds during the COVID-19 pandemic: analysis and technology implications using the SAMR framework
Authors: Yin Kathleen , Coiera Enrico , Jung Joshua , Rohilla Urvashi , Lau Annie Y S
Published: April 2022

Objective

To understand the nature of health consumer self-management workarounds during the COVID-19 pandemic; to classify these workarounds using the Substitution, Augmentation, Modification, and Redefinition (SAMR) framework; and to see how digital tools had assisted these workarounds.

Materials and Methods

We assessed 15 self-managing elderly patients with Type 2 diabetes, multiple chronic comorbidities, and low digital literacy. Interviews were conducted during COVID-19 lockdowns in May–June 2020 and participants were asked about how their self-management had differed from before. Each instance of change in self-management were identified as consumer workarounds and were classified using the SAMR framework to assess the extent of change. We also identified instances where digital technology assisted with workarounds.

Results

Consumer workarounds in all SAMR levels were observed. Substitution, describing change in work quality or how basic information was communicated, was easy to make and involved digital tools that replaced face-to-face communications, such as the telephone. Augmentation, describing changes in task mechanisms that enhanced functional value, did not include any digital tools. Modification, which significantly altered task content and context, involved more complicated changes such as making video calls. Redefinition workarounds created tasks not previously required, such as using Google Home to remotely babysit grandchildren, had transformed daily routines.

Discussion and Conclusion

Health consumer workarounds need further investigation as health consumers also use workarounds to bypass barriers during self-management. The SAMR framework had classified the health consumer workarounds during COVID, but the framework needs further refinement to include more aspects of workarounds.
Thermal energy performance due to convection process of nanofluid in a porous medium due to split lid motion in a right triangular enclosure
Authors: Ullah M Zaka , Hussain S T , Haq Rizwan Ul , Alzahrani A Khamis , Mallawi Fouad
Published: April 2022

In the current phenomena, a study is carried out for the convection process of nanofluid within the porous media enclosed in a triangular permeable cavity. The heat generation effect within the nanofluid is developed when the two heat sources are applied through the split lids. To analyse the behaviour of nanofluids and steam lines, we have considered an elliptic (cold, adiabatic, and heated)-shaped obstacle that is placed inside the cavity. Mathematical modelling is carried out through continuity, momentum equation, and energy equations in the form of a system of non-linear partial differential equations. These equations are produced after incorporating the relations of viscosity, density, shapes of nanoparticle, and thermal conductivity for nanofluids Constraints are adjusted according to the forced convection due to the upper moving wall of the cavity. Four different cases of the upper double lid-driven wall are considered. All the emerging parameters, namely Reynolds number $( {25 \le {\rm{Re}} \le 750} ),$ heat generation $( { - {{10}^4} \le Q \le 40} ),\ $ nanoparticle volume fraction $\ ( {0 \le \phi \le 0.2} )$, and Darcy number ${10^{ - 5}} \le Da \le {10^{ - 3}}$, are analysed through variation of velocities, temperature profile, isotherms, and streamlines. Various cases at the surface of the inner elliptical obstacle provide significant contributions in the variation of heat transfer rate and velocity profiles. Nanoparticles provide a considerable increase in the heat transfer rate. The Darcy number shows the substantial variation in the formation of the isothermal region. An increase in heat generation parameter Q provides an improvement in temperature distribution inside the cavity and it also caused the formation of a single isothermal region around the heated obstacle.
Synonymous Variants: Necessary Nuance in Our Understanding of Cancer Drivers and Treatment Outcomes
Authors: Kaissarian Nayiri M , Meyer Douglas , Kimchi-Sarfaty Chava
Published: April 2022

Once called “silent mutations” and assumed to have no effect on protein structure and function, synonymous variants are now recognized to be drivers for some cancers. There have been significant advances in our understanding of the numerous mechanisms by which synonymous single nucleotide variants (sSNVs) can affect protein structure and function by affecting pre-mRNA splicing, mRNA expression, stability, folding, micro-RNA binding, translation kinetics, and co-translational folding. This review highlights the need for considering sSNVs in cancer biology to gain a better understanding of the genetic determinants of human cancers and to improve their diagnosis and treatment. We surveyed the literature for reports of sSNVs in cancer and found numerous studies on the consequences of sSNVs on gene function with supporting in vitro evidence. We also found reports of sSNVs that have statistically significant associations with specific cancer types but for which in vitro studies are lacking to support the reported associations. Additionally, we found reports of germline and somatic sSNVs that were observed in numerous clinical studies and for which in silico analysis predicts possible effects on gene function. We provide a review of these investigations and discuss necessary future studies to elucidate the mechanisms by which sSNVs disrupt protein function and play a role in tumorigeneses, cancer progression, and treatment efficacy. As splicing dysregulation is one of the most well-recognized mechanisms by which sSNVs impact protein function, we also include our own in silico analysis for predicting which sSNVs may disrupt pre-mRNA splicing.
Impacted common bile duct stone managed by hepaticoduodenostomy
Authors: Weledji Elroy Patrick , Mbengawo Ndiformuche Zikirou , Zouna Frank
Published: April 2022

A bypass procedure such as a hepaticoduodenostomy may be an alternative to the traditional choledochoduodenostomy in the management of the retained, impacted distal common bile duct stone especially in the presence of sepsis. In low-resource settings with lack of fluoroscopy, fibreoptic instruments (choledoscope) or radiologically guided wire baskets or balloons for stone retrieval, there are operative hazards in blindly exploring the common bile duct. We present herein a hepaticoduodenostomy performed for a retained, impacted distal common bile duct stone in a low-resource setting with a good outcome. This impacted stone had complicated an open cholecystectomy for acute cholecystitis by causing the dehiscence of the cystic duct stump as a result of distal biliary obstruction.
A Deployed Soldier Presenting With Dyspnea and Orthopnea Due to a Morgagni Hernia
Authors: McMahon Michael , Kniery Kevin , Wingard Daniel , Destree Craig , Brown Colin , Nessler Thomas G
Published: April 2022

Shortness of breath is an important complaint in the austere setting with a broad differential diagnosis. The difficulty of deployed patient movement and lack of diagnostic testing at treatment sites complicates its evaluation. This case highlights a young Soldier presenting with shortness of breath caused by a Morgagni hernia. A 25-year-old deployed male presented with a 1-month history of dyspnea with exertion and right-sided chest tightness. After initial diagnoses of bronchitis, later chest radiographs demonstrated a linear opacity in the right middle lobe (RML). The patient was transferred to a higher level of care where a chest computer tomography scan was consistent with Morgagni hernia. Morgagni hernias can present with a wide variety of clinical complaints, including gastrointestinal symptoms, dyspnea, and chest pain. A lack of familiarity among providers who care for adults and the nonspecific nature of the symptoms frequently cause a diagnostic delay in diagnosis. CXR is helpful in this diagnosis, although this case demonstrates that this hernia may appear similar to RML atelectasis or pneumonia.6 Computed tomography remains the modality of choice to confirm the diagnosis, as well as provide anatomical details and rule out complications. While most experts agree that Morgagni hernias should be surgically repaired, the optimal surgical technique remains uncertain.3 Despite its rarity, Morgagni hernia is important to consider in a broad range of clinical presentations. Its nonspecific symptoms, combined with radiographs that can mimic other disease entities, can lead to a delay in diagnosis, mistreatment, prolonged patient suffering, and complications.
Circular polarimetry of suspect wind-accreting magnetic pre-polars
Authors: Hakala Pasi , Parsons Steven G , Marsh Thomas R , Gänsicke Boris T , Ramsay Gavin , Schwope Axel , Hermes J J
Published: April 2022

We present results from a circular polarimetric survey of candidate detached magnetic white dwarf – M dwarf binaries obtained using the Nordic Optical Telescope, La Palma. We obtained phase resolved spectropolarimetry and imaging polarimetry of seven systems, five of which show clearly variable circular polarisation. The data indicate that these targets have white dwarfs with magnetic field strengths >80 MG. Our study reveals that cyclotron emission can dominate the optical luminosity at wavelengths corresponding to the cyclotron emission harmonics, even in systems where the white dwarfs are only wind-accreting. This implies that a very significant fraction of the stellar wind of the companion star is captured by the magnetic white dwarf reducing the magnetic braking in pre-cataclysmic variables (CVs). Furthermore, the polarimetric confirmation of several detached, wind-accreting magnetic systems provides observational constraints on the models of magnetic CV evolution and white dwarf magnetic field generation. We also find that the white dwarf magnetic field configuration in at least two of these systems appears to be very complex.
Pharmacokinetics, pharmacodynamics, and safety of single-dose subcutaneous sarilumab with or without methotrexate in Japanese patients with rheumatoid arthritis: Two single-dose studies
Authors: Ishii Tomonori , Sato Yukio , Munakata Yasuhiko , Kajiwara Miyuki , Takahashi Yoshinori , van Hoogstraten Hubert , Xu Christine , Kato Naoto , Takahashi Toshiya
Published: April 2022

Objectives

To assess the safety and pharmacokinetics (PK) of single-dose subcutaneous (SC) sarilumab or tocilizumab SC ± methotrexate (MTX) and to assess the pharmacodynamics (PD) of sarilumab SC or tocilizumab SC monotherapy in Japanese rheumatoid arthritis (RA) patients.

Methods

TDU13402 was a randomized, double-blind, placebo-controlled, single-ascending dose Phase 1 study (NCT01850680). Twenty-four patients (6 per treatment group) received sarilumab 50, 100, or 200 mg plus MTX or placebo (2 per cohort) on Day (D) 1; PK and safety were assessed through D57. PDY14191 was a randomized, open-label, single-dose study (NCT02404558). Thirty patients (15 per arm) received sarilumab 150 mg or tocilizumab 162 mg on D1; PK, PD, and safety were assessed through D43.

Results

TDU13402: mean serum sarilumab exposure increased in a greater than dose proportional manner from 50 to 200 mg dose with no clinically meaningful increase in treatment-emergent adverse events (TEAEs). PDY14191: PK profiles of single-dose sarilumab 150 mg or tocilizumab 162 mg were similar; some numerical differences in PD profiles and TEAEs were observed. Neutrophil count decrease/neutropenia was the most frequently reported TEAE with sarilumab treatment in both studies.

Conclusions

PK, PD, and safety profiles of single-dose sarilumab SC with/without MTX were consistent with results anticipated in Japanese patients with RA.
Dynamic and facilitated binding of topoisomerase accelerates topological relaxation
Authors: Michieletto Davide , Fosado Yair A G , Melas Elias , Baiesi Marco , Tubiana Luca , Orlandini Enzo
Published: April 2022

How type 2 Topoisomerase (TopoII) proteins relax and simplify the topology of DNA molecules is one of the most intriguing open questions in genome and DNA biophysics. Most of the existing models neglect the dynamics of TopoII which is expected of proteins searching their targets via facilitated diffusion. Here, we show that dynamic binding of TopoII speeds up the topological relaxation of knotted substrates by enhancing the search of the knotted arc. Intriguingly, this in turn implies that the timescale of topological relaxation is virtually independent of the substrate length. We then discover that considering binding biases due to facilitated diffusion on looped substrates steers the sampling of the topological space closer to the boundaries between different topoisomers yielding an optimally fast topological relaxation. We discuss our findings in the context of topological simplification in vitro and in vivo.
KmerKeys: a web resource for searching indexed genome assemblies and variants
Authors: Pavlichin Dmitri S , Lee HoJoon , Greer Stephanie U , Grimes Susan M , Weissman Tsachy , Ji Hanlee P
Published: April 2022

K-mers are short DNA sequences that are used for genome sequence analysis. Applications that use k-mers include genome assembly and alignment. However, the wider bioinformatic use of these short sequences has challenges related to the massive scale of genomic sequence data. A single human genome assembly has billions of k-mers. As a result, the computational requirements for analyzing k-mer information is enormous, particularly when involving complete genome assemblies. To address these issues, we developed a new indexing data structure based on a hash table tuned for the lookup of short sequence keys. This web application, referred to as KmerKeys, provides performant, rapid query speeds for cloud computation on genome assemblies. We enable fuzzy as well as exact sequence searches of assemblies. To enable robust and speedy performance, the website implements cache-friendly hash tables, memory mapping and massive parallel processing. Our method employs a scalable and efficient data structure that can be used to jointly index and search a large collection of human genome assembly information. One can include variant databases and their associated metadata such as the gnomAD population variant catalogue. This feature enables the incorporation of future genomic information into sequencing analysis. KmerKeys is freely accessible at https://kmerkeys.dgi-stanford.org.
Cell type identification in spatial transcriptomics data can be improved by leveraging cell-type-informative paired tissue images using a Bayesian probabilistic model
Authors: Zubair Asif , Chapple Richard H , Natarajan Sivaraman , Wright William C , Pan Min , Lee Hyeong-Min , Tillman Heather , Easton John , Geeleher Paul
Published: April 2022

Spatial transcriptomics technologies have recently emerged as a powerful tool for measuring spatially resolved gene expression directly in tissues sections, revealing cell types and their dysfunction in unprecedented detail. However, spatial transcriptomics technologies are limited in their ability to separate transcriptionally similar cell types and can suffer further difficulties identifying cell types in slide regions where transcript capture is low. Here, we describe a conceptually novel methodology that can computationally integrate spatial transcriptomics data with cell-type-informative paired tissue images, obtained from, for example, the reverse side of the same tissue section, to improve inferences of tissue cell type composition in spatial transcriptomics data. The underlying statistical approach is generalizable to any spatial transcriptomics protocol where informative paired tissue images can be obtained. We demonstrate a use case leveraging cell-type-specific immunofluorescence markers obtained on mouse brain tissue sections and a use case for leveraging the output of AI annotated H&E tissue images, which we used to markedly improve the identification of clinically relevant immune cell infiltration in breast cancer tissue. Thus, combining spatial transcriptomics data with paired tissue images has the potential to improve the identification of cell types and hence to improve the applications of spatial transcriptomics that rely on accurate cell type identification.
VRprofile2: detection of antibiotic resistance-associated mobilome in bacterial pathogens
Authors: Wang Meng , Goh Ying-Xian , Tai Cui , Wang Hui , Deng Zixin , Ou Hong-Yu
Published: April 2022

VRprofile2 is an updated pipeline that rapidly identifies diverse mobile genetic elements in bacterial genome sequences. Compared with the previous version, three major improvements were made. First, the user-friendly visualization could aid users in investigating the antibiotic resistance gene cassettes in conjunction with various mobile elements in the multiple resistance region with mosaic structure. VRprofile2 could compare the predicted mobile elements to the collected known mobile elements with similar architecture. A new mobilome indicator was proposed to give an overall estimation of the mobilome size in individual bacterial genomes. Second, the relationship between antibiotic resistance genes, mobile elements, and host strains would be efficiently examined with the aid of predicted strain's sequence typing, the incompatibility group and the transferability of plasmids. Finally, the updated back-end database, MobilomeDB2, now collected nearly a thousand active mobile elements retrieved from literature or based on prediction. The pre-computed results of the antibiotic resistance gene-carrying mobile elements of >5500 ESKAPEE genomes were also provided. We expect that VRprofile2 will provide better support for researchers interested in bacterial mobile elements and the dissemination of antibiotic resistance. VRprofile2 is freely available to all users without any login requirement at https://tool2-mml.sjtu.edu.cn/VRprofile.
Intraspecific de novo gene birth revealed by presence–absence variant genes in Caenorhabditis elegans
Authors: Lee Bo Yun , Kim Jun , Lee Junho
Published: April 2022

Genes embed their evolutionary history in the form of various alleles. Presence–absence variants (PAVs) are extreme cases of such alleles, where a gene present in one haplotype does not exist in another. Because PAVs may result from either birth or death of a gene, PAV genes and their alternative alleles, if available, can represent a basis for rapid intraspecific gene evolution. Using long-read sequencing technologies, this study traced the possible evolution of PAV genes in the PD1074 and CB4856 C. elegans strains as well as their alternative alleles in 14 other wild strains. We updated the CB4856 genome by filling 18 gaps and identified 46 genes and 7,460 isoforms from both strains not annotated previously. We verified 328 PAV genes, out of which 46 were C. elegans-specific. Among these possible newly born genes, 12 had alternative alleles in other wild strains; in particular, the alternative alleles of three genes showed signatures of active transposons. Alternative alleles of three other genes showed another type of signature reflected in accumulation of small insertions or deletions. Research on gene evolution using both species-specific PAV genes and their alternative alleles may provide new insights into the process of gene evolution.
Clinical Characteristics, Health Care Utilization, and Outcomes Among Patients in a Pilot Surveillance System for Invasive Mold Disease—Georgia, United States, 2017–2019
Authors: Gold Jeremy A W , Revis Andrew , Thomas Stepy , Perry Lewis , Blakney Rebekah A , Chambers Taylor , Bentz Meghan L , Berkow Elizabeth L , Lockhart Shawn R , Lysen Colleen , Nunnally Natalie S , Jordan Alexander , Kelly Hilary C , Montero Alejandro J , Farley Monica M , Oliver Nora T , Pouch Stephanie M , Webster Andrew S , Jackson Brendan R , Beer Karlyn D
Published: April 2022

Background

Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system.

Methods

During 2017–2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician’s diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases.

Results

Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n = 66 [63.5%]), mucormycosis (n = 8 [7.7%]), and fusariosis (n = 4 [3.8%]); the most frequently affected body sites were pulmonary (n = 66 [63.5%]), otorhinolaryngologic (n = 17 [16.3%]), and cutaneous/deep tissue (n = 9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit–level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients.

Conclusions

IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases.
Osteoradionecrosis of the craniotomy flap: a rare complication of stereotactic radiosurgery
Authors: Schlafstein Ashley , Shu Hui-Kuo
Published: April 2022

Osteoradionecrosis (ORN), ischemic necrosis of irradiated bone without evidence of persisting or recurrent tumor, is a known complication of radiation therapy. ORN of the skull has not been reported following stereotactic radiosurgery (SRS). We report two cases of ORN of the skull following SRS for recurrent meningiomas post-resection. Both patients developed ORN in their craniotomy flaps in areas that received high doses of radiation due to their proximity to the recurrent tumors. In each case, the ORN was asymptomatic and was detected on surveillance magnetic resonance imaging. Both patients were followed closely with imaging that ultimately revealed either stability or improvement in the ORN, confirming the diagnosis without the need for biopsy. The cases reveal a role for close imaging surveillance instead of immediate biopsy in patients with new enhancement involving bone in high-dose radiation treatment regions.
Strong site-specific association of pharyngeal cultures with the onset of psoriatic arthritis and psoriasis, regardless of pathogen
Authors: Thrastardottir Telma , Meer Elana , Hauksdottir Arna , Gudbjornsson Bjorn , Kristinsson Sigurdur Yngvi , Ogdie Alexis , Love Thorvardur Jon
Published: April 2022

Objectives

The objective of this study was to evaluate any association between culture site / culture result / pathogen and incident PsA or psoriasis.

Methods

Records of all samples sent for culture from a large population during a 3-year period were linked with nationwide registry data on diagnoses and death over a 15-year period. The main outcomes of interest were incident diagnoses of PsA and psoriasis, defined by International Classification of Diseases (ICD) codes. The effect of culture site, culture result (positive vs negative), and pathogen (Streptococcus vs negative culture) on the risk of developing PsA and psoriasis was calculated using Cox proportional hazards models adjusted for age and gender.

Results

A total of 313 235 bacterial cultures from 128 982 individuals were analysed. Comparing individuals with pharyngeal cultures to those with urine cultures, the hazard ratio for incident PsA was 8.78 [95% confidence interval (CI) 3.23, 23.91] and for incident psoriasis it was 8.00 (95% CI 5.28, 12.12). Most of the risk was concentrated in the first 50 days after the culture date. Increased risk was also found when comparing individuals with cultures from the pharynx with those with cultures from the nasopharynx and blood. An association with streptococci was not found, neither in the pharynx nor at any other site. A positive bacterial culture from any site was associated with reduced risk for both PsA and psoriasis.

Conclusion

There is a strong site-specific association between pharyngeal culture samples and an increased risk of PsA and psoriasis, regardless of the pathogen. This may indicate that the site of infection, rather than the pathogen, is associated with increased risk.
A number of legal principles have been reaffirmed in relation to section 47 applications arising from In The Matter The XYZ Trusts
Authors: Bernard Stephanie
Published: April 2022

In The Matter The XYZ Trusts is an important case because it confirmed a number of very useful legal principles. In relation to applications pursuant to section 47 of the Bermuda Trustee Act 1975, it confirmed that such applications may be used in series for the blessing of various stages of a large transaction, the test to be used when asking for the blessing of a momentous decision and that in relation to the variation of a trust it will not create a new settlement. Finally, it confirmed the Bermuda Court’s willingness to issue confidentiality orders in cases involving the administration of private trusts.
Three new clades of putative viral RNA-dependent RNA polymerases with rare or unique catalytic triads discovered in libraries of ORFans from powdery mildews and the yeast of oenological interest Starmerella bacillaris
Authors: Forgia Marco , Chiapello M , Daghino Stefania , Pacifico D , Crucitti D , Oliva D , Ayllon M , Turina M , Turina M
Published: April 2022

High throughput sequencing allowed the discovery of many new viruses and viral organizations increasing our comprehension of virus origin and evolution. Most RNA viruses are currently characterized through similarity searches of annotated virus databases. This approach limits the possibility to detect completely new virus-encoded proteins with no detectable similarities to existing ones, i.e. ORFan proteins. A strong indication of the ORFan viral origin in a metatranscriptome is the lack of DNA corresponding to an assembled RNA sequence in the biological sample. Furthermore, sequence homology among ORFans and evidence of co-occurrence of these ORFans in specific host individuals provides further indication of a viral origin. Here, we use this theoretical framework to report the finding of three conserved clades of protein-coding RNA segments without a corresponding DNA in fungi. Protein sequence and structural alignment suggest these proteins are distantly related to viral RNA-dependent RNA polymerases (RdRP). In these new putative viral RdRP clades, no GDD catalytic triad is present, but the most common putative catalytic triad is NDD and a clade with GDQ, a triad previously unreported at that site. SDD, HDD, and ADD are also represented. For most members of these three clades, we were able to associate a second genomic segment, coding for a protein of unknown function. We provisionally named this new group of viruses ormycovirus. Interestingly, all the members of one of these sub-clades (gammaormycovirus) accumulate more minus sense RNA than plus sense RNA during infection.
Burnout Research at a Crossroads
Authors: Cunningham Tim , Pappas Sharon H.
Published: April 2022

We have enough evidence that burnout exists—let's investigate solutions.
Maintaining the Watch
Authors: Morris Kristine
Published: April 2022

One nurse's struggle to care for an aging parent.
Persistent But Not Transient Acute Kidney Injury Was Associated With Lower Transplant-Free Survival in Patients With Acute Liver Failure: A Multicenter Cohort Study*
Authors: Cardoso Filipe S. , Fidalgo Pedro , Bagshaw Sean M. , Gottfried Michelle , Tujios Shannan , Olson Jody C. , Lee William M. , Karvellas Constantine J. ,   for the U.S. Acute Liver Failure Study Group
Published: April 2022

OBJECTIVES:

Acute liver failure (ALF) is an orphan disease often complicated by acute kidney injury (AKI). We assessed the impact of transient versus persistent AKI on survival in patients with ALF.

DESIGN:

International multicenter retrospective cohort.

SETTING:

U.S. ALF Study Group prospective registry.

PATIENTS:

Patients with greater than or equal to 18 years and ALF in the registry from 1998 to 2016 were included. Patients with less than 3 days of follow-up, without kidney function evaluation on day 3, or with cirrhosis were excluded.

INTERVENTIONS:

AKI was defined by Kidney Disease Improving Global Outcomes guidelines on day 1. Kidney recovery was defined on day 3 as transient AKI, by a return to no-AKI within 48 hours or persistent AKI if no such recovery or renal replacement therapy (RRT) was observed. Primary outcome was transplant-free survival (TFS) at 21 days.

MEASUREMENTS AND MAIN RESULTS:

Among 1,071 patients with ALF, 339 (31.7%) were males, and median (interquartile range) age was 39 years (29–51 yr). Acetaminophen-related ALF was found in 497 patients (46.4%). On day 1, 485 of 1,071 patients (45.3%) had grade 3–4 hepatic encephalopathy (HE), 500 of 1,070 (46.7%) required invasive mechanical ventilation (IMV), 197 of 1,070 (18.4%) were on vasopressors, and 221 of 1,071 (20.6%) received RRT. On day 1, 673 of 1,071 patients (62.8%) had AKI. On day 3, 72 of 1,071 patients (6.7%) had transient AKI, 601 of 1,071 (56.1%) had persistent AKI, 71 of 1,071 (6.6%) had late onset AKI, and 327 of 1,071 (30.5%) remained without AKI. Following adjustment for confounders (age, sex, race, etiology, HE grade, use of IMV and vasopressors, international normalized ratio, and year), although persistent acute kidney injury (adjusted odds ratio [aOR] [95% CI] 0.62 [0.44–0.88]) or late onset AKI (aOR [95% CI] 0.48 [0.26–0.89]) was associated with lower TFS, transient AKI was not (aOR [95% CI] 1.89 [0.99–3.64]).

CONCLUSIONS:

In a multicenter cohort of patients with ALF, persistent but not transient AKI was independently associated with lower short-term TFS.
Toxoplasma gondii Infection and Aggression in Autistic Children
Authors: Hamid Najmeh , Azizy Boshra , Hamidinejad Hossein
Published: April 2022

Background:

Toxoplasmosis is an infectious disease caused by the obligatory intracellular parasite Toxoplasma gondii. The main aim of this study was to evaluate a possible relationship between aggression in autistic children with infection by T. gondii.

Methods:

The research design was an analytical (comparative) cross sectional study. The participants included (N = 100) subjects (50 autistic and 50 normal children) between 3 and 12 years old. They were matched for age, socioeconomic status, lack of physical and mental illness. The instruments were preschool aggression scale and enzyme-linked immunosorbent assay procedure to essay the blood sample test. Five milliliters of blood samples were collected to assess the presence of T. gondii infection.

Results:

The results showed that autistic children had a higher rate of infection by T. gondii than normal children. Furthermore, children infected with T. gondii were more aggressive than the noninfected group.

Conclusions:

In autistic children, T. gondii infection was significantly higher than in the normal group. Also, autistic children who were infected with the parasite were more aggressive.
Subsartorius Fascial Plane Hydrodissection as Novel Treatment for Hunter's Canal Syndrome
Authors: Eliot Hu Yao-Wen , Ridings Catherine
Published: April 2022

Saphenous entrapment neuropathy in the distal thigh most commonly occurs at Hunter's canal and is characterized by neurologic symptoms distal to the midthigh in the saphenous nerve distribution. Presented is a 23-year-old active duty female service member with left medial knee pain worse with knee flexion and extension. Evaluation raised suspicion for saphenous nerve entrapment at Hunter's canal, and ultrasound-guided subsartorius fascial plane hydrodissection was performed in addition to focused rehabilitation of the adductor and core musculature. No reports of this treatment have been published to date. This case introduces ultrasound-guided subsartorius fascial plane hydrodissection as novel treatment in Hunter's canal syndrome.
Incremental Effects of Subsequent Concussions on Cognitive Symptoms in the Sport Concussion Assessment Tool
Authors: Chen Jian , Oddson Bruce , Skrinar Hannah
Published: April 2022

Objective:

Patients who are fully recovered from a concussion may still be more vulnerable in the face of subsequent concussions. This study examines symptoms associated with repeated concussions in young and otherwise healthy adults.

Design:

Cross sectional.

Setting:

Institutional study at a university setting.

Participants:

University students with a history of concussion.

Independent Variables:

Participants were grouped based on numbers of concussions.

Main Outcome Measures:

The impact of incremental concussion on symptom clusters in Sport Concussion Assessment Tools 5 and Spearman ranking correlation coefficients between symptom clusters.

Results:

One hundred thirty-five participants reported having had 1 concussion, 63 reported 2 concussions, 50 reported 3 concussions, and 43 reported 4 to 6 concussions. Total severity scores over the range of concussion number (1, 2, 3, and greater than 3) did not show a clear incremental effect. However, average scores of cognitive symptoms rose with each subsequent concussion (P ≤ 0.05). The largest incremental effect observed was that of second concussions on emotional symptom scores (t = 5.85, P < 0.01). Symptoms in the emotional and cognitive clusters were the most correlated regardless of the number of reported concussions; the correlations were lowest with symptoms associated with sensitivity to light or noise.

Conclusions:

The incremental rise of cognitive symptom scores with each concussion affirms the importance of cognitive impairment in concussion assessment and implies a cumulative brain vulnerability that persists even after symptom resolution. The cognitive-emotional symptom clusters may reflect underlying concussion-induced impairments in the corticostriatothalamocortical (CSTC) networks, although sensitivity symptoms are potentially attributable to different neural correlates.
Outcome and Determinants of Neutropenic Enterocolitis in Pediatric Cancer Patients
Authors: Sahoo Debasish , Seth Rachna , Chaudhry Rama , Naranje Priyanka , Ahuja Vineet , Dwivedi Sada N. , Gupta Aditya K. , Meena Jagdish P.
Published: April 2022

Background:

Neutropenic enterocolitis (NEC) is a dreaded complication of chemotherapy. There is scant literature regarding incidence, clinical features, and determinants. The understanding of gut dysbiosis in NEC and pediatric cancer is evolving.

Methods:

Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for NEC with contrast-enhanced computed tomography abdomen. Clinical, imaging, and laboratory features were analyzed. Fecal samples were analyzed for fecal calprotectin by sandwich enzyme-linked immunoassay and gut microbiota by conventional culture and compared with healthy controls and children without NEC.

Results:

NEC was diagnosed in 44 children based on clinical and imaging features with incidence of 7.4% (4 had recurrent episodes). Common manifestations included fever (98%), pain abdomen (88%), and diarrhea (83%). Hypoalbuminemia was observed in 78% of patients. Large bowel involvement (94%) with diffuse bowel involvement (63%) and pancolitis (64%) were common. Fecal calprotectin was significantly elevated in NEC group than non-NEC group and healthy controls (median: 87, 53, and 42 µg/g, respectively). A higher degree of gut dysbiosis was observed in children with NEC with higher isolation of Bacteroides and infrequent isolation of Lactobacilli. Mortality rate of 23% was observed. Only the presence of free fluid predicted higher mortality. Though levels of fecal calprotectin and gut dysbiosis were higher in NEC, they did not increase mortality. Isolation of Bacteroides and absence of Lactobacilli predicted a longer duration of intravenous alimentation.

Conclusions:

NEC caused significant morbidity and mortality in pediatric cancer patients. Gut dysbiosis was significantly higher in NEC group suggesting a role in pathogenesis and influencing outcome. This highlights the role of targeted interventions towards gut dysbiosis like prebiotics and probiotics.
Hematologic Complications Associated With Intra-arterial Chemotherapy for Retinoblastoma Treatment: A Single Institution Experience
Authors: Sanati-Mehrizy Ali , Ghosh Taumoha , Peterson Eric , Starke Robert M. , Harbour J. William , Corrales-Medina Fernando F.
Published: April 2022

Retinoblastoma (RB) is the most common intraocular pediatric malignancy. Advancements in intra-arterial chemotherapy (IAC) for treatment of RB have resulted in dramatic improvement in eye salvage rates. Data regarding IAC outcomes and associated hematologic toxicities are limited. The objective of this retrospective study was to analyze baseline characteristics, efficacy, and hematologic complications associated with IAC treatment in children with RB at a single international referral institution. Ninety-five sessions of IAC were performed in 28 patients. Mean age at RB diagnosis was 12.5 months (SD, 9.2 mo). Fourteen patients had bilateral RB. IAC agents included melphalan, carboplatin, and topotecan. The most common regimens were triple-agent IAC and single-agent melphalan (66.3% and 15.8%, respectively). Median number of IAC sessions was 3 (mean: 3.39, range: 1 to 9). Eye salvage rate was 83.7% with an overall survival rate of 100% at a median follow-up of 29 months (mean: 29.8 mo, range: 1 to 63 mo). A total of 26 patients (92.9%) experienced at least 1 hematologic toxicity during their treatment course Prevalence of neutropenia, anemia, and thrombocytopenia were 89.3%, 85.7%, and 25%, respectively. While IAC is effective in salvaging most eyes with advanced intraocular RB, over half of patients experienced clinically significant neutropenia and anemia. Clinicians should be vigilant in monitoring patients for IAC-related complications.
Prevalence of Corneal Topographic Patterns in Ectatic Corneal Diseases
Authors: Shah Zalak , Singh Shwetambari , Shilpy Neha , Purohit Dipali
Published: April 2022

SIGNIFICANCE

The article highlights various topographic patterns and their prevalence in a large spectrum of ectatic corneal diseases (ECDs). Knowledge of these patterns can help clinicians for quicker diagnosis and selection of appropriate contact lens design.

PURPOSE

This study aimed to determine various corneal topography patterns and their prevalence in patients with ECDs who visited a tertiary eye hospital in western India.

METHODS

Keratoconus, pellucid marginal degeneration, keratoglobus, and post–refractive surgery progressive corneal ectasia are considered under ECDs. This cross-sectional retrospective study reviewed records of 632 consecutive patients with clinical ECDs at their first presentation. The right eye was considered for pattern analysis. In cases with suspected or forme fruste ectasia in the right eye, the fellow eye was considered. A sagittal map with standard scale of Atlas 9000 topographer (Carl Zeiss Meditec AG, Jena, Germany) was used for pattern analysis. They were classified into 18 categories and grouped under five groups. The prevalence of these patterns was calculated and assessed with 95% confidence interval (CI).

RESULTS

The mean ± SD age of patients was 23.6 ± 8.2 years. The highest prevalence was of asymmetric patterns (39.6% [95% CI, 35.7 to 43.5%]; asymmetric bowtie [AB] with steepest radial axis index [SRAX], 18.8%; AB with inferior steep, 16.0%; AB with superior steep [SS], 3.2%; symmetric bowtie with SRAX, 1.6%) and of central or paracentral patterns (28.6% [95% CI, 25.1 to 32.3%]; inferior steep, 12.2%; heart, 7.4%; oval, 4.1%; symmetric bowtie, 2.4%; round, 1.6%; irregular, 0.9%) followed by advanced patterns (17.3% [95% CI, 14.4 to 20.4%; nonmeasurable, 5.4%; globus, 4.9%; indiscriminate, 7.0%). The peripheral patterns were 11.7% (95% CI, 9.3 to 14.4%) (claw, 6.3%; junctional, 3.2%; butterfly, 1.9%; SS, 0.3%). Rare patterns were 2.8% (95% CI, 1.7 to 4.5%) (superior [junctional, claw, and heart], AB with SS with SRAX, and AB with SRAX located temporally).

CONCLUSIONS

Asymmetric and central or paracentral are the most common patterns in our study. The higher prevalence of advanced patterns indicates the need for earlier diagnosis of ECDs in our population. The peripheral patterns also have significant prevalence.
Late-Onset Pyloric Stenosis and Intussusception With Final Diagnosis of Food Proteins’ Hypersensitivity in Schaaf-Yang Syndrome: A Case Report
Authors: Mari Alessandra , Sartorio Marco Ugo Andrea , Degrassi Irene , D’Auria Enza , Fiori Laura , Dilillo Dario , Agostinelli Marta , Pendezza Erica , Bosetti Alessandra , Maestri Luciano , Pelizzo Gloria , Zuccotti Gian Vincenzo , Verduci Elvira
Published: April 2022

Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder whose clinical spectrum includes neurodevelopment delay, dysmorphic features, and gastrointestinal symptoms such as feeding difficulties, gastroesophageal reflux, and chronic constipation. Given the small number of patients diagnosed with this syndrome, our aim is to describe novel clinical features that have not yet been reported. The patient we are describing is a 14-year-old male affected by a severe form of SYS. Initial clinical presentation included respiratory distress at birth, feeding difficulties, and neurodevelopmental delay. Since the age of 8 months, he had been tube fed with a semi-elemental formula, and this was well tolerated. At 9 years of age, the pathological mutation (variant p.Val701fs in MAGEL2 gene) associated with SYS was diagnosed. At 13 years of age, he presented severe gastrointestinal symptoms associated to progressive feeding difficulties. He also suffered from recurrent pancreatitis, late-onset pyloric stenosis and intussusception. Histology showed duodenal villous atrophy with a negative serology for celiac disease. Food protein’s hypersensitivity was diagnosed and symptoms resolved after starting an elemental formula.