bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of SARS-CoV-2 Vaccines against Omicron Infection and Severe Events: A Systematic Review and Meta-Analysis of Test-Negative Design Studies
Authors: Song Shangchen , Madewell Zachary J. , Liu Mingjin , Longini Ira M. , Yang Yang
Published: February 2023

Background

Evaluating vaccine effectiveness (VE) of a full vaccine series and booster doses against COVID-19 is important for health decision-making.

Methods

We systematically searched papers that evaluated VE of SARS-CoV-2 vaccines on PubMed, Web of Science, Cochrane Library, Google Scholar, Embase, Scopus, and preprint servers (bioRxiv and medRxiv) published from November 26th, 2021 to June 27th, 2022 (for full doses and first booster), and to January 8th, 2023 (for the second booster). The pooled VE against Omicron-associated symptomatic or any infection as well as severe events are estimated in a meta-analysis framework.

Results

From 2,552 citations identified, a total of 42 were included. The vaccination of the first booster provided stronger protection against Omicron than the full doses alone, shown by the VE estimates of 53.1% (95% CI: 48.0−57.8) vs. 28.6% (95% CI: 18.5−37.4) against infection and 82.5% (95% CI: 77.8−86.2) vs. 57.3% (95% CI: 48.5−64.7) against severe disease. The second booster offered strong protection among adults within 60 days of vaccination against infection (VE=53.1%, 95% CI: 48.0−57.8) and severe disease (VE=87.3% (95% CI: 75.5-93.4), comparable to the first booster with corresponding VE estimates of 59.9% against infection and 84.8% against severe disease. The VEs of the booster doses against severe disease among adults sustained beyond 60 days, 77.6% (95% CI: 69.4−83.6) for the first and 85.9% (95% CI: 80.3−89.9) for the second booster. The VE against infection was less sustainable regardless of dose type. Pure mRNA vaccines provided comparable protection to partial mRNA vaccines, but both provided higher protection than non-mRNA vaccination.

Conclusion

One or two booster doses of current SARS-CoV-2 vaccines provide considerable protection against Omicron infection and substantial and sustainable protection against Omicron-induced severe clinical outcomes.

Funding

US CDC U01 CK000670
CHARACTERISTICS OF ACUTE PSYCHIATRIC DISORDERS IN PATIENTS WITH COVID-19 IN A THIRD-LEVEL HOSPITAL IN PERU
Authors: De La Cruz-Amador Marcionila Estelita , Aguirre-Quispe Wilfor , Apaza-Aceituno Edwin Genaro , Valdivia-Francia María Francesca
Published: February 2023

Objective

To describe the sociodemographic and clinical characteristics of acute psychiatric disorders in COVID-19 patients in an emergency department at a national reference psychiatry and mental health hospital.

Methods

A descriptive observational study was performed. Data were collected from medical records of patients admitted by emergency according to the International Classification of Diseases (ICD-11). The group of patients with a first acute psychiatric episode vs. patients with more than one acute psychiatric episode were compared.

Results

110 patients were included; 61.8% corresponded to the female sex and the mean age was 36 ± 12.3 years. 49.1% corresponded to schizophrenia, followed by acute polymorphic psychotic disorder (13.6%), bipolar disorder (10%), and depressive episodes (7.3%). Psychotic disorders and depressive episodes occurred in a higher percentage in the group with a first episode, 42.4% (p< 0.001), and 15.2% (p< 0.001), respectively. The episodes of schizophrenia were higher in the group of patients with previous episodes (63.6%).

Conclusions

A higher frequency of cases of acute psychotic disorder and depressive disorders was found as the first episode in patients with COVID-19 infection; however, within the group with previous episodes, greater predominance of patients with acute disorders due to schizophrenia was found.
Cost-effectiveness of use of 20-valent pneumococcal conjugate vaccine among adults in Germany
Authors: Kühne Felicitas , Achtert Katharina , Püschner Franziska , Urbanski-Rini Dominika , Schiller Juliane , Mahar Ernestine , Friedrich Josephine , Atwood Mark , Sprenger Ralf , Vietri Jeffrey , von Eiff Christof , Theilacker Christian
Published: February 2023

Objectives

Despite national recommendations for use of pneumococcal vaccines, rates of community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) remain high in Germany. New pneumococcal conjugate vaccines (PCVs) with expanded coverage have the potential to reduce the pneumococcal disease burden among adults.

Methods

Using a Markov model, we evaluated the lifetime outcomes/costs comparing 20-valent PCV (PCV20) with standard of care (SC) vaccination for prevention of CAP and IPD among adults aged ≥60 years and at-risk adults aged 18-59 years in Germany. PCV20 also was compared with sequential vaccination with 15-valent PCV (PCV15) followed by (→) PPSV23 in a scenario analysis.

Results

Over the course of a lifetime (82 years), use of PCV20 vs. SC would prevent 54,333 hospitalizations, 26,368 outpatient CAP cases, 10,946 disease-related deaths yield 74,694 additional life-years (LYs), while lowering total medical costs by 363.2M €. PCV20 remained cost saving (i.e., dominant) versus SC even in numerous sensitivity analyses. In the scenario analysis, PCV20 also showed to be cost-saving compared to using PCV15→PPSV23.

Conclusions

One dose of PCV20 among adults aged ≥60 years and adults aged 18-59 years with moderate- and high-risk conditions would substantially reduce pneumococcal disease, save lives, and be cost saving compared with SC.

HIGHLIGHTS

Pneumococcal disease causes significant morbidity and mortality among adults in Germany

New, higher valent vaccines have the potential to reduce disease burden and associated costs in vulnerable populations

ver a lifetime, 20-valent pneumococcal conjugate vaccine was found to be cost-saving compared with current standard of care for pneumococcal disease prevention among adults in Germany
WITHDRAWN: Exposure to an enriched environment improves colonic epithelial barrier integrity and attenuates mouse experimental colitis by modulating a Myc-driven gene regulatory network
Authors: Villaseñor-Toledo Tomás , Valle-Garcia David , Pop Romana T. , Osio-Becerro Víctor , Meza-Sosa Karla F , Serrano Carolina , Díaz de León-Guerrero Sol , Hernández-Pando Rogelio , Nava Porfirio , Kuijjer Marieke L. , Pérez-Martínez Leonor , Pedraza-Alva Gustavo
Published: February 2023

Withdrawal Statement

The authors have withdrawn their manuscript owing to erroneous labeling in two figures that have recently come to light. Experiments aiming to confirm the data presented are underway. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Inhibition ofhaao-1enhances oxidative stress response by activating hormetic redox signaling inC. elegans
Authors: Castro-Portuguez Raul , Raymond Kayla M. , Thullen Emma , Hendrickson Alana M. , Freitas Samuel , Hull Bradford , Meyers Jeremy B. , Thorns Niall , Gardea Emily A. , Dang Hope , Espejo Luis S. , Sutphin George L.
Published: February 2023

3-hydroxyanthranilate 3,4-dioxygenase (HAAO) is an intermediate enzyme in the conversion from tryptophan (TRP) to nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway. The kynurenine pathway is the sole‘de novo’NAD+biosynthetic pathway from ingested tryptophan. Inhibition of several enzymatic steps in the kynurenine pathway increases lifespan inDrosophila melanogaster, Saccharomyces cerevisiae, andCaenorhabditis elegans. Knockout or knockdown ofhaao-1, theC. elegansgene encoding HAAO, or supplementation of its substrate metabolite 3-hydroxyanthranilic acid (3HAA), has been shown to promote healthy lifespan extension; however, the underlying mechanism remains unknown. In the present study, we report thathaao-1knockdown induces oxidative stress resistance against several reactive oxygen species (ROS) inducing agents by activating the Nrf2/SKN-1 oxidative stress response pathway. An examination of the redox state of animals with reducedhaao-1suggests that activation of the Nrf2/SKN-1 pathway is mediated by shifting the balance toward generation of ROS, generating a hormetic effect. Our results identify a novel mechanism for an endogenous metabolite (3HAA) that activates the oxidative stress response. These results provide a conceptual basis by which modulation of the kynurenine pathway can promote healthy aging and enhanced stress resistance.

Graphical Abstract

Highlights

Knockdown ofhaao-1promotes oxidative stress resistance.

Knockdown ofhaao-1activates the Nrf2/SKN-1 oxidative stress response.

The shift in redox balance inhaao-1knockout animals suggests a hormetic mechanism for oxidative stress resistance.
Spatially localized expression of glutamate decarboxylasegadBinEscherichia coliO157:H7 microcolonies in hydrogel matrix
Authors: Martin Cédric Saint , Caccia Nelly , Darsonval Maud , Grégoire Marina , Combeau Arthur , Jubelin Grégory , Dubois-Brissonnet Florence , Leroy Sabine , Briandet Romain , Desvaux Mickaël
Published: February 2023

Functional diversity within isogenic spatially organized bacterial populations has been shown to trigger emergent community properties such as stress tolerance. Taking advantage of confocal laser scanning microscopy combined with a transcriptional fluorescent fusion reporting at single cell scale the expression of the glutamic acid decarboxylasegadBinE. coliO157:H7, it was possible to visualize for the first-time spatial patterns of bacterial gene expression in microcolonies grown in a gelled matrix. ThegadBgene is involved inE. colitolerance to acidic conditions and its strong over-expression was observed locally on the periphery of embedded microcolonies grown in acidic hydrogels. This spatialization ofgadBexpression did not correlate with live/dead populations that appeared randomly distributed in the colonies. While the planktonic population of the pathogens was eradicated by an exposition to a pH of 2 (HCl) for 4h, mimicking a stomachal acidic stress, bacteria grown in gel-microcolonies were poorly affected by this treatment, in particular in conditions wheregadBwas spatially overexpressed. Consequences of these results for food safety are further discussed.
A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia
Authors: Fischer Friedericke , Ernst Laurin , Frey Anna , Holstein Katrin , Prasad Deepti , Weichselberger Vanessa , Balaji Ramya , Classen Anne-Kathrin
Published: February 2023

Tissue-intrinsic error-correction mechanisms allow epithelial cells to detect aberrant neighboring cells and cause their removal from the tissue. The molecular mechanisms which grant cells the ability to compare their internal states is unknown. Here we demonstrate that comparison of cell identity, created by cell-fate-specifying transcription factors and patterning pathways, is conveyed through a specific set of cell surface molecules. We demonstrate that Drosophila imaginal discs express a range of cell surface molecules previously implicated in neuronal axon guidance processes, such as members of the Robo, Teneurin, Ephrin, Toll-like or atypical Cadherin families. Expression of these molecules is regulated by intrinsic fate-patterning pathways of the disc but also by aberrant expression of oncogenic RasV12. Importantly, mosaic clones deregulating individual cell surface molecules are sufficient to induce all hallmarks of ’interface surveillance’, a tissue-intrinsic error-correction mechanism previously shown to be induced by cells with aberrant activation of fate-patterning pathways. Specifically, cells with deregulated expression of Robo2 and Robo3 induce actomyosin enrichment, bilateral JNK signaling and apoptosis at mosaic clone interfaces in imaginal discs. Moreover, deregulation of Robo2 levels, which is normally expressed in a complex endogenous pattern, induces these interface surveillance hallmarks in a Robo2-pattern-specific manner. Taken together, our work indicates that these cell surface molecules mediate cell fate recognition in epithelial tissues and thereby contribute to the maintenance of epithelial health by initiating detection and removal of aberrant cells during development and adult tissue homeostasis.
Redox Regulation of m6A Methyltransferase METTL3 in Human β-cells Controls the Innate Immune Response in Type 1 Diabetes
Authors: De Jesus Dario F. , Zhang Zijie , Brown Natalie K. , Li Xiaolu , Gaffrey Matthew J. , Kahraman Sevim , Wei Jiangbo , Hu Jiang , Basile Giorgio , Xiao Ling , Rana Tariq M. , Mathews Clayton , Powers Alvin C. , Atkinson Mark A. , Eizirik Decio L. , Dhe-Paganon Sirano , Parent Audrey V. , Qian Wei-Jun , He Chuan , Kulkarni Rohit N.
Published: February 2023

Type 1 Diabetes (T1D) is characterized by autoimmune-mediated destruction of insulin-producing β-cells. Several observations have renewed interest in the innate immune system as an initiator of the disease process against β-cells. Here, we show that N6-Methyladenosine (m6A) is an adaptive β-cell safeguard mechanism that accelerates mRNA decay of the 2’-5’-oligoadenylate synthetase (OAS) genes to control the antiviral innate immune response at T1D onset. m6A writer methyltransferase 3 (METTL3) levels increase drastically in human and mouse β-cells at T1D onset but rapidly decline with disease progression. Treatment of human islets and EndoC-βH1 cells with pro-inflammatory cytokines interleukin-1 β and interferon α mimicked the METTL3 upregulation seen at T1D onset. Furthermore, m6A-sequencing revealed the m6A hypermethylation of several key innate immune mediators includingOAS1, OAS2,andOAS3in human islets and EndoC-βH1 cells challenged with cytokines. METTL3 silencing in human pseudoislets or EndoC-βH1 cells enhanced OAS levels by increasing its mRNA stability upon cytokine challenge. Consistently,in vivogene therapy, to prolong Mettl3 overexpression specifically in β-cells, delayed diabetes progression in the non-obese diabetic (NOD) mouse model of T1D by limiting the upregulation ofOaspointing to potential therapeutic relevance. Mechanistically, the accumulation of reactive oxygen species blocked METTL3 upregulation in response to cytokines, while physiological levels of nitric oxide promoted its expression in human islets. Furthermore, for the first time to our knowledge, we show that the cysteines in position C276 and C326 in the zinc finger domain of the METTL3 protein are sensitive to S-nitrosylation (SNO) and are significant for the METTL3 mediated regulation of OAS mRNA stability in human β-cells in response to cytokines. Collectively, we report that m6A regulates human and mouse β-cells to control the innate immune response during the onset of T1D and propose targeting METTL3 to prevent β-cell death in T1D.
Bipalium admarginatumde Beauchamp, 1933 (Platyhelminthes, Tricladida, Geoplanidae) in Malaysia, with molecular characterisation including the mitogenome
Authors: Michelle Soo Oi Yoon , Gastineau Romain , Verdon George , Winsor Leigh , Justine Jean-Lou
Published: February 2023

We present here the first observation ofBipalium admarginatumde Beauchamp, 1933 since its original description 90 years ago. Three specimens were found on Perhentian Kecil Island, off Terengganu State, Malaysia and photographed in the field, and two were collected. This report thus includes the first colour photographs published for this species, from a locality close to the type-locality, Tioman Island (which is ca. 200 km south of the locality in this study, on the east coast of Peninsula Malaysia). We describe the external morphology and colour pattern of the species, which correspond well to the original description, itself based only on two preserved specimens. We performed an in-depth molecular characterisation of the species, including its complete mitochondrial genome, the 18S sequence and elongation 1 alpha sequence. In addition, EF1a sequences were also retrieved for 5 additional geoplanid species. NotRNA-Thrcould be detected in the mitogenome ofB. admarginatum, a lack already reported in several species of geoplanids, but we found a 13 bp sequence that contains the anticodon loop and seems to be conserved among geoplanids and might thus possibly represent a non-canonical undetected tRNA. We discuss the difficulties encountered in trying to reconstruct the cluster of nuclear ribosomal genes, a problem already mentioned for other Triclads. Three phylogenies, based respectively on all mitochondrial proteins, 18S, and EF1a, were computed; the position ofB. admarginatumwithin the Bipaliinae was confirmed in each tree, as sister-group to various bipaliine species according to the sequences available for each tree.
A trait or a state - how consistent are tail biting phenotypes in pigs?
Authors: Chou Jen-Yun , D’Eath Rick B. , Sandercock Dale A. , O’Driscoll Keelin
Published: February 2023

The physiological, psychological and behavioural traits of tail biting/bitten pigs have been widely studied, with most research focusing on identifying traits to predict tail biting phenotypes (biters, victims, or uninvolved ‘neutrals’). However, it is not clear if these traits persist once pigs are no longer involved in performing or receiving tail bites. This study investigated whether there was a difference in behavioural responses to a novel object test (NOT) between pigs which were tail biting performers (BITER), recipients (VICTIM), or not involved in the biting events (NEUTRAL). We then investigated whether these differences in responses were still evident six weeks later, when tail biting was less prevalent. We hypothesised that biters would exhibit more behaviours indicative of boldness, but also stress, than victims or neutrals, and that these differences would still be present later. A total of 120 undocked pigs (BITER, n = 48; VICTIM, N = 48; NEUTRAL, n = 24; 60 male, 60 female) were selected for testing. At the time of the first test (one week after pigs were moved into the finisher house at 12 weeks of age; T1), the prevalence of tail biting peaked. The same test was repeated six weeks later (T2) when biting had eased. Each pig was tested separately in a novel arena. After a minute of habituation, a brush head was introduced by dropping it down from above, at which point the 5 min test began. A saliva sample was taken immediately before the habituation (baseline) and after each test to evaluate cortisol concentration. Direct continuous behaviour observation was conducted. Overall, salivary cortisol concentrations were higher after than before the NOT (P< 0.001), although VICTIM pigs had a reduced elevation in cortisol after the test (P= 0.02) compared to BITER and NEUTRAL pigs in T2. Between phenotypes, baseline saliva cortisol concentrations were similar. BITER pigs approached the object quicker than VICTIM pigs (P = 0.01), but also had more high-pitched vocalisations (P < 0.01), but these differences observed in T1 were no longer present in T2. The results suggested that the NOT was sensitive to detect different levels of behavioural response; however, differences in BITER pigs’ behavioural responses were transient and did not persist once biting behaviour ceased. The long-term consequence of chronic stress caused by being tail bitten was manifested in VICTIM pigs’ blunted cortisol elevation six weeks later, after severe tail biting events.
Comparison of sporulation and germination conditions forClostridium perfringensstrains
Authors: Liggins Marc , Ramírez Norma Ramírez , Abel-Santos Ernesto
Published: February 2023

Clostridium perfringensis a spore forming, obligate anaerobe, Gram-positive bacterium that causes a range of diseases in humans and animals. The infectious form ofC. perfringensis the spore, a structure that is derived from the vegetative cell under conditions of nutrient deprivation. The first step inC. perfringenspathogenesis is the differentiation of spores into replicating bacteria. Previous work in analyzingC. perfringensspore germination has produced contradictory, strain-specific results. Hence, we analyzed the requirements for spore formation and germination in seven differentC. perfringensstrains. Our data showed thatC. perfringenssporulation conditions are strain specific, but germination responses are homogenous.C. perfringensspores can germinate using two distinct pathways. The first germination pathway (the amino acid-only pathway or AA) requires L-alanine, L-phenylalanine, and sodium ions (Na+) as co-germinants. L-arginine is not a required germinant but potentiates germination. The AA pathway is inhibited by aromatic amino acids and potassium ions (K+). Bicarbonate (HCO3-), on the other hand, bypasses potassium-mediated inhibition ofC. perfringensspore germination through the AA pathway. The second germination pathway (the bile salt and amino acid pathway or BA) is more promiscuous and is activated by several bile salts and amino acids. In contrast to the AA pathway, the BA pathway is insensitive to Na+, but can be activated by either K+or HCO3-. We hypothesize thatC. perfringensmay have evolved these two distinct germination pathways to ensure spore response to different host environments.

Manuscript contribution to the field

Clostridium perfringensis a ubiquitous bacterium that can infect a wide variety of animal hosts, including humans.C. perfringenscounts with a veritable arsenal of toxins that are differentially expressed depending on the host infected. Besides toxin production,C. perfringenscan also form dormant and resistant spores that serve as infective vehicles.C. perfringensspores need to germinate back into vegetative cells to cause disease. Befitting to its wide host range,C. perfringensspore germination seems to use strain specific. In this study, we tested the ability of sevenC. perfringensstrains to produce spores under different conditions. We also tested the requirements for spore germination. We found that whileC. perfringenssporulation was highly varied, the germination response for all strains could be divided into two distinct pathways. SinceC. perfringensspores need to germinate to cause infection, understanding the germination behavior could lead to approaches for the prevention of diseases in humans and veterinary animals.
Investigating insecticide susceptibility status of adult mosquitoes against some class of insecticides in Osogbo metropolis, Osun State, Nigeria
Authors: Raheem H. O. , Iwalewa Z. O. , Busari L. O. , Fasasi K. A. , Adeleke M. A.
Published: February 2023

The study evaluates the resistance and susceptibility of adult femaleAnopheles gambiaes. l.,Aedes aegyptiandCulex quinquefasciatusmosquitoes sourced within Osogbo metropolis, Osun State, Nigeria to four groups of insecticides [Permethrin, Deltamethrin, Pirimiphos-methyl and DDT (Dichlorodiphenyltrichloroethan)] and the distribution of their larval habitat within the metropolis. Mosquito larvae of the three genera were collected during the wet season and reared to adult stage in the laboratory. Emerged adult female mosquitoes were exposed to insecticide impregnated papers of the four insecticide groups for 60mins using WHO kits to determine the knock down rate (kdr). Thereafter, they were to holding tubes and left for 24hrs to assess their resistance and susceptibility according to the WHO protocol. Four types of larval habitats were identified (tires, ground pools, gutters and plastic containers).Anopheles gambiaes. l. showed the greatest resistance to Permethrin (49%) (p=0.04, p<0.05) while the highest susceptibility was recorded with Pirimiphos-methyl (69%) with the lowest against Permethrin (16%) (P=0.002; p<0.05). The greatest resistance ofA. aegyptiwas against OC-Control (45%) (p=0.031; p<0.05). Permethrin had the highest susceptibility (60%) againstA. aegyptiwhile OC-control had the lowest (11%) (p= 0.005; p< 0.05).Culex quinquefasciatushad a lesser resistance to OC-control (38%) as compared withAedes aegypti(45%). However, it was most least susceptible to Pirimiphos-methyl (52%) and DDT (17%) respectively (p=0.013; p<0.05). The susceptibility ofA. gambiaes. l. andC. quinquefasciatusto Pirimiphos-methyl andA. aegyptito Permethrin is an indication of the possibility of success if employed for vector control ofA. gambiaes. l.,C. quinquefasciatusandA. aegyptirespectively. This could be through their inclusion as active ingredients in insecticide treated nets (ITNs) and indoor residual spray (IRS) with a view to abating malaria and other life-threatening mosquito-borne diseases constituting global public health scourge.
Starvation induces extracellular accumulation of polyphosphate inDictyostelium discoideumto inhibit macropinocytosis, phagocytosis, and exocytosis
Authors: Rijal Ramesh , Ismail Issam , Jing Shiyu , Gomer Richard H.
Published: February 2023

Dictyostelium discoideumis a soil-dwelling unicellular eukaryote that accumulates extracellular polyphosphate (polyP). At high cell densities, when the cells are about to overgrow their food supply and starve, the corresponding high extracellular concentrations of polyP allow the cells to preemptively anticipate starvation, inhibit proliferation, and prime themselves to begin development. In this report, we show that starvedD. discoideumcells accumulate cell surface and extracellular polyP. Starvation reduces macropinocytosis, exocytosis, and phagocytosis, and we find that these effects require the G protein-coupled polyP receptor (GrlD) and two enzymes, Polyphosphate kinase 1 (Ppk1), which is required for synthesizing intracellular polyP, cell surface polyP, and some of the extracellular polyP, and Inositol hexakisphosphate kinase (I6kA), which is required for cell surface polyP and polyP binding to cells, and some of the extracellular polyP. PolyP reduces membrane fluidity, and we find that starvation reduces membrane fluidity, and this effect requires GrlD and Ppk1 but not I6kA. Together, these data suggest that in starved cells, extracellular polyP decreases membrane fluidity, possibly as a protective measure. In the starved cells, sensing polyP appears to decrease energy expenditure from ingestion, and decrease exocytosis, to both decrease energy expenditures and retain nutrients.
BEAM: a combinatorial recombinase toolbox for binary gene expression and mosaic analysis
Authors: Greig Luciano C. , Woodworth Mollie B. , Poulopoulos Alexandros , Lim Stephanie , Macklis Jeffrey D.
Published: February 2023

Genetic mosaic analysis, in which mutant cells reside intermingled with wild-type cells, is a powerful experimental approach, but has not been widely used in mice because existing genome-based strategies require complicated and protracted breeding schemes. We have developed an alternative approach termed BEAM (for Binary Expression Aleatory Mosaic) that relies on sparse recombinase activation to generate two genetically distinct, non-overlapping populations of cells for comparative analysis. Following delivery of DNA constructs by transfection or viral transduction, combinatorial recombinase activity generates two distinct populations of cells labeled with either green or red fluorescent protein. Any gene of interest can be mis-expressed or deleted in one population for comparison with intermingled control cells. We have extensively optimized and characterized this system bothin vitroandin vivo, and demonstrate its power for investigating cell autonomy, identifying temporally or spatially aberrant phenotypes, revealing changes in cell proliferation or death, and controlling for procedural variability.
Evaluation of SARS-CoV-2 isolation in cell culture from nasal/nasopharyngeal swabs or saliva specimens of patients with COVID-19
Authors: Yazawa Shunsuke , Yamazaki Emiko , Saga Yumiko , Itamochi Masae , Inasaki Noriko , Shimada Takahisa , Oishi Kazunori , Tani Hideki
Published: February 2023

It has been revealed that SARS-CoV-2 can be efficiently isolated from clinical specimens such as nasal/nasopharyngeal swabs or saliva in cultured cells. In this study, we examined the efficiency of viral isolation including SARS-CoV-2 mutant strains between nasal/nasopharyngeal swab or saliva specimens. Furthermore, we also examined the comparison of viral isolation rates by sample species using simulated specimens for COVID- 19. As a result, it was found that the isolation efficiency of SARS-CoV-2 in the saliva specimens was significantly lower than that in the nasal/nasopharyngeal swab specimens. In order to determine which component of saliva is responsible for the lower isolation rate of saliva specimens, we tested the abilities of lactoferrin, amylase, cathelicidin, and mucin, which are considered to be abundant in saliva, to inhibit the infection of SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Lactoferrin and amylase were found to inhibit SARS-CoV-2pv infection. In conclusion, even if the same number of viral genome copies was detected by the real-time RT-PCR test, infection of SARS-CoV-2 present in saliva is thought to be inhibited by inhibitory factors such as lactoferrin and amylase, compared to nasal/nasopharyngeal swab specimens.
A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141-DCs as the key cellular components in septic prognosis
Authors: Liang Qiao , Wang Lei , Xu Jing , Lin Anqi , Wu Yongzheng , Tao Qing , Zhang Bin , Min Haiyan , Song Shiyu , Gao Qian
Published: February 2023

Differential body responses to various stresses, infectious or noninfectious, govern clinical outcomes ranging from asymptoma to death. However, the common molecular and cellular nature of the stress responsome across different stimuli is not described. In this study, we compared the expression behaviors between burns and COVID-19 infection by choosing the transcriptome of peripheral blood from related patients as the analytic target since the blood cells reflect the systemic landscape of immune homeostasis. We identified an immune co-stimulator (CD86)-centered network, named stress-response core (SRC), which coordinated multiple immune processes and was robust in membership and highly related to the clinical traits in both burns and COVID-19. An independent whole blood single-cell RNA sequencing of COVID-19 patients demonstrated that the monocyte-dendritic cell (Mono-DC) wing was the major cellular source of the SRC, among which the higher expression of the SRC in the monocyte was associated with the asymptomatic COVID-19 patients, while the quantity-restricted and function-defected CD1C-CD141-DCs were recognized as the key signature which linked to bad consequences in COVID-19. Specifically, the proportion of the CD1C-CD141-DCs and their SRC expression levels were step-wise reduced along with worse clinic conditions while the sub-cluster of CD1C-CD141-DCs of the critical COVID-19 patients was characterized of IFN signaling quiescence, high mitochondrial metabolism and immune-communication inactivation. Thus, our study identified an expression-synchronized and function-focused gene network which was decreased under burns and COVID-19 stress and argued the CD1C-CD141-DC as the prognosis-related cell population which might serve as a new target of diagnosis and therapy.
Crystal structures of 4-(2/3-methoxyphenoxy)phthalonitrile
Authors: Erzunov Dmitry , Rassolova Anastasia , Rumyantsev Roman , Maizlish Vladimir , Tikhomirova Tatiana , Vashurin Arthur
Published: February 2023

The syntheses and crystal structures are reported of 4-phenoxy-substituted phthalonitriles with methoxy groups in the ortho- and meta-positions of the terminal benzene rings, respectively, namely, 4-(2-methoxyphenoxy)phthalonitrile and 4-(3-methoxyphenoxy)phthalonitrile, both C15H10N2O2. The https://journals.iucr.org/e/issues/2023/03/00/molecular structure was determined using the single-crystal X-ray diffraction method. It is shown that short contacts play a more decisive role in the molecular packing compared to van der Waals interactions.
Warming undermines emergence success in a threatened alpine stonefly: A multi‐trait perspective on vulnerability to climate change
Authors: Shah Alisha A. , Hotaling Scott , Lapsansky Anthony B. , Malison Rachel L. , Birrell Jackson H. , Keeley Tylor , Giersch J. Joseph , Tronstad Lusha M. , Woods H. Arthur
Published: February 2023

Vulnerability to warming is often assessed using short‐term metrics such as the critical thermal maximum (CTMAX), which represents an organism's ability to survive extreme heat. However, the long‐term effects of sub‐lethal warming are an essential link to fitness in the wild, and these effects are not adequately captured by metrics like CTMAX.

The meltwater stonefly,Lednia tumana, is endemic to high‐elevation streams of Glacier National Park, MT, USA, and has long been considered acutely vulnerable to climate‐change‐associated stream warming. As a result, in 2019, it was listed as Threatened under the U.S. Endangered Species Act. This presumed vulnerability to warming was challenged by a recent study showing that nymphs can withstand short‐term exposure to temperatures as high as ~27°C. But whether they also tolerate exposure to chronic, long‐term warming remained unclear.

By measuring fitness‐related traits at several ecologically relevant temperatures over several weeks, we show thatL. tumanacannot complete its life‐cycle at temperatures only a few degrees above what some populations currently experience.

The temperature at which growth rate was maximized appears to have a detrimental impact on other key traits (survival, emergence success and wing development), thus extending our understanding ofL. tumana's vulnerability to climate change.

Our results call into question the use of CTMAXas a sole metric of thermal sensitivity for a species, while highlighting the power and complexity of multi‐trait approaches to assessing vulnerability.

Read the freePlain Language Summaryfor this article on the Journal blog.
Withdrawn: ‘Downregulation of circPPFIA1 elevates radiosensitivity via miR‐1299–mediated TXNRD1 inhibition in oesophageal squamous cell carcinoma’, Weihui Yu, Ke Ning, Jincheng Xiao, Qiwen Bai and Chenyang Guo. (https://onlinelibrary.wiley.com/doi/10.1111/1440‐1681.13751).
Authors: Yu Weihui , Ning Ke , Bai Qiwen , Guo Chenyang
Published: February 2023

The above article, published online on 16 February 2023 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the journal Editor in Chief, Yang Yang, and John Wiley & Sons Ltd. The withdrawal has been agreed following no response from the authors to requests to sign the journal's publishing license agreement.
Change from within: Shia Seminarians' Responses to Contemporary Religious and Social Challenges
Authors: Akbar Ali
Published: February 2023

This article demonstrates how some contemporary scholars, operating from within the traditional Shiʿi establishment, have paved the way for new interpretations of Islam in general and Shiʿism in particular. To do so, the article focuses on three specific themes: the notion of the (im)purity of non‐Muslims, rulings on apostasy and precepts related to women's rights. Following a brief explanation of the history of Shiʿism, the article addresses each of three aforementioned themes in turn. In each section, the article explains how the relevant theme was approached by earlier religious scholars, and how it has been treated differently by some contemporary reformist Shiʿi clerics. While not claiming the trends of thought instigated by some contemporary ʿulamāʾ are entirely homogeneous with liberal ideas about human rights, this article provides examples of Shiʿi legal standpoints being reformed to meet the challenges of the contemporary world.
The Missing Generation: Grandparents and Agency in Early Modern England
Authors: CAPP BERNARD
Published: February 2023

Grandparents have been largely overlooked in the otherwise rich historiography of the family in early modern England. This article shows how many were able to play significant roles in family life, in both emotional and practical terms. Some forged close bonds with their young grandchildren, or took them in for a period to relieve hard‐pressed parents, while others were willing to raise and educate the orphaned. Some also provided moral or religious guidance, assuming responsibilities conventionally assigned to godparents, and in some cases even challenging parental decisions of which they disapproved. Grandchildren were almost always remembered in wills, with testators also careful to protect the interests of any potentially at risk. The article then turns to explore the role of grandparents acting as welfare providers, whether voluntarily or through a court order, for grandchildren left as orphans or born to unmarried mothers. It assesses the often contentious issue of grandparents’ moral and legal responsibilities under the parish relief system established by the Poor Law in 1601, and disputes between the paternal and maternal kin. Finally, the article touches briefly on grandparents as repositories of information, whose memories and experience could be of value to their community as well as to their own families.
A needle in a haystack: A new metabarcoding approach to survey diversity at the species level of Arcellinida (Amoebozoa: Tubulinea)
Authors: González‐Miguéns Rubén , Cano Emilio , Guillén‐Oterino Antonio , Quesada Antonio , Lahr Daniel J. G. , Tenorio‐Rodríguez Daniel , de Salvador‐Velasco David , Velázquez David , Carrasco‐Braganza María Isabel , Patterson R. Timothy , Lara Enrique , Singer David
Published: February 2023

Environmental DNA‐based diversity studies have increased in popularity with the development of high throughput sequencing technologies. This permits the potential simultaneous retrieval of vast amounts of molecular data from many different organisms and species, thus contributing to a wide range of biological disciplines. Environmental DNA protocols designed for protists often focused on the highly conserved small subunit of the ribosome gene, that does not permit species‐level assignments. On the other hand, eDNA protocols aiming at species‐level assignments allow a fine level ecological resolution and reproducible results. These protocols are currently applied to organisms living in marine and shallow lotic freshwater ecosystems, often in a bioindication purpose. Therefore, in this study, we present a species‐level eDNA protocol designed to explore diversity of Arcellinida (Amoebozoa: Tubulinea) testate amoebae taxa that is based on mitochondrial cytochrome oxidase subunit I (COI). These organisms are widespread in lentic water bodies and soil ecosystems. We applied this protocol to 42 samples from peatlands, estuaries and soil environments, recovering all the infraorders in Glutinoconcha (with COI data), except for Hyalospheniformes. Our results revealed an unsuspected diversity in morphologically homogeneous groups such as Cylindrothecina, Excentrostoma or Sphaerothecina. With this protocol we expect to revolutionize the design of modern distributional Arcellinida surveys. Our approach involves a rapid and cost‐effective analysis of testate amoeba diversity living in contrasted ecosystems. Therefore, the order Arcellinida has the potential to be established as a model group for a wide range of theoretical and applied studies.
Disseminated Mycobacterium chelonae infection complicating rheumatoid arthritis: A case report and review of the literature
Authors: Pham James P. , Boot Madison , Stefani Maurizio , Chapman Scott , Byrne Anthony , Abdel‐Shaheed Christina , Girgis Laila
Published: February 2023

Introduction

Rheumatoid arthritis (RA) may predispose patients to opportunistic infections—either from innate immune dysregulation, or as a result of immunosuppressant use to treat the RA. Particularly concerning opportunistic infections are those caused by non‐tuberculous mycobacterial (NTM) organisms, the incidence of which has been increasing in epidemiological studies. Despite this, guidelines on the management of patients with RA who develop NTM infections are scarce, particularly with respect to immunosuppressant regimen modulation and duration of antibiotic therapy.

Case Report

Herein, we present a case of disseminated Mycobacterium chelonae infection, manifesting as arthralgia and cutaneous nodules.

Discussion

In addition, a review of the literature was conducted to Preferred Reporting Items for Systemic Reviews and Meta‐Analyses guidelines to identify similar cases in the literature—revealing that all RA‐associated M. Chelonae infections occurred in immunosuppressed patients (the majority with corticosteroids or tumor necrosis factor inhibitors), and considerable heterogeneity in management approaches. Further research regarding risk factors, preventative approaches and best management of such NTM infections in vulnerable patients with RA is required in order to establish consensus guidelines and consistency.
Pretreatment changes in drinking: A test of a tailored treatment approach
Authors: Stasiewicz Paul R. , Bradizza Clara M. , Lucke Joseph F. , Zhao Junru , Dermen Kurt H. , Linn Braden K. , Slosman Kim S. , LaBarre Charles
Published: February 2023

Background

Pretreatment reductions in drinking are well documented and have been demonstrated to predict posttreatment drinking outcomes. Making use of the predictive value of pretreatment change has great appeal in settings that place a premium on efficient clinical decisions regarding appropriate type and intensity of treatment.

Methods

This study investigates whether different types and intensities of treatment are appropriate and beneficial for individuals entering treatment for an alcohol use disorder (AUD; N = 201) who make more vs. less pretreatment change in their drinking during a 2‐month pretreatment period. Based on an algorithm derived from pilot research, we derived two independent pretreatment change arms that we called Substantial Change and Minimal Change. Each arm was a parallel, sequentially randomized design consisting of a treatment group and an active control. The Substantial Change arm compared six sessions of relapse prevention treatment (RPT) with 12 sessions of cognitive behavioral therapy for AUD (CBT) as an active control. Both CBT and RPT occurred over a 12‐week period. The Minimal Change arm compared 12 sessions of an integrated motivational intervention combined with CBT (MI/CBT) with 12 sessions of CBT as an active control. The outcome variables were changes in number of days abstinent (NDA) and number of days heavy drinking (NDH) per week.

Results

For the Substantial Change arm, a noninferiority analysis revealed that six sessions of RPT were noninferior to 12 sessions of CBT at each posttreatment assessment for both NDA and NDH. For the Minimal Change arm, a superiority analysis failed to detect that MI/CBT was superior to CBT at any posttreatment assessment for both NDA and NDH.

Conclusions

In the substantial change arm, results suggest that offering a less intensive initial treatment, like RPT, may lower costs and conserve clinical resources. In the Minimal Change arm, results indicate the need to continue searching for a treatment or treatment enhancements to improve alcohol outcomes.
Latent classes of neurodevelopmental profiles and needs in children and adolescents with prenatal alcohol exposure
Authors: McLachlan Kaitlyn , Minhas Meenu , Ritter Chantel , Kennedy Kathleen , Joly Vannesa , Faitakis Martina , Cook Jocelynn , Unsworth Kathy , MacKillop James , Pei Jacqueline
Published: February 2023

Background

Fetal alcohol spectrum disorder (FASD) resulting from prenatal alcohol exposure (PAE) is a common neurodevelopmental disorder, but substantial interindividual heterogeneity complicates timely and accurate assessment, diagnosis, and intervention. The current study aimed to identify classes of children and adolescents with PAE assessed for FASD according to their pattern of significant neurodevelopmental functioning across 10 domains using latent class analysis (LCA), and to characterize these subgroups across clinical features.

Methods

Data from the Canadian National FASD Database, a large ongoing repository of anonymized clinical data received from diagnostic clinics across Canada, was analyzed using a retrospective cross‐sectional cohort design. The sample included 1440 children and adolescents ages 6 to 17 years (M = 11.0, SD = 3.5, 41.7% female) with confirmed PAE assessed for FASD between 2016 and 2020.

Results

Results revealed an optimal four‐class solution. The Global needs group was characterized by high overall neurodevelopmental impairment considered severe in nature. The Regulation and Cognitive needs groups presented with moderate but substantively distinguishable patterns of significant neurodevelopmental impairment. The Attention needs group was characterized by relatively low probabilities of significant neurodevelopmental impairment. Both the Global and Regulation needs groups also presented with the highest probabilities of clinical needs, further signifying potential substantive differences in assessment and intervention needs across classes.

Conclusions

Four relatively distinct subgroups were present in a large heterogeneous sample of children and adolescents with PAE assessed for FASD in Canada. These findings may inform clinical services by guiding clinicians to identify distinct service pathways for these subgroups, potentially increasing access to a more personalized treatment approach and improving outcomes.
Early‐onset recurrent panniculitis as a phenotype of NLRC4‐associated autoinflammatory syndrome: Characterization of pathogenicity of the p.Ser445ProNLRC4 variant
Authors: Gil‐Lianes Javier , Gariup Giuseppe , Iranzo‐Fernández Pilar , Mensa‐Vilaró Anna , Peñín‐Franch Alejandro , Hurtado‐Navarro Laura , Pelegrin Pablo , Aróstegui Juan I.
Published: February 2023

Monoallelic NLRC4 gain‐of‐function variants cause an inflammasomopathy with diverse clinical forms including infantile enterocolitis, recurrent macrophage activation syndrome, cold‐induced urticaria‐like lesions (or familial‐cold autoinflammatory syndrome, FCAS4), and painful subcutaneous nodules. Here, we identified a large family with six consecutive generations affected. Genetic analyses detected the heterozygous p.Ser445Pro NLRC4 variant in three patients, which has been previously reported in a Dutch family with FCAS4. We aimed to describe the clinicopathological features and the functional consequences of the detected NLRC4 variant. Patients presented an early‐onset (3 months–6 years) inflammatory disease characterized by recurrent panniculitis, fever and arthralgia. Histopathological examination showed perivascular and interstitial lymphohistiocytic infiltrates in the dermis and mixed panniculitis. Functional analysis supported the conclusion that the p.Ser445Pro NLRC4 variant leads to a constitutive activation of NLRC4‐inflammasome and increased plasma levels of IL‐18. Prompt recognition of early‐onset panniculitis through clinicopathological examination and laboratory biomarkers may allow targeted therapies.