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Influenzavirus is among the most relevant candidates for a next pandemic. We review here the phylogeny of former influenza pandemics, and discuss candidate lineages. After briefly reviewing the other existing antiviral options, we discuss in detail the evidences supporting the efficacy of passive immunotherapies against influenzavirus, with a focus on convalescent plasma. [ABSTRACT FROM AUTHOR]

This article discusses the use of robot-assisted retrograde intrarenal surgery (roboRIRS) for the treatment of urinary stones. The article explains that while flexible ureteroscopy (fURS) is commonly used for stone treatment, it has ergonomic limitations and can be challenging in complicated cases. The introduction of robotics in endourological interventions, such as roboRIRS, aims to improve surgical outcomes, ergonomics, and surgeon health. The article describes the ILY® robotic system, a compact trolley mini-console operated remotely by a wireless controller, which offers potential benefits in terms of ergonomics and reduced radiation exposure. The article presents a case series of six patients who underwent roboRIRS using the ILY robot, demonstrating its feasibility and safety. The authors suggest that further investigations are needed to evaluate the real-life benefits and cost-effectiveness of this technology. [Extracted from the article]

This article is a systematic review and meta-analysis of randomized controlled trials (RCTs) that assess the safety of COVID-19 convalescent plasma (CCP). The review found that CCP is generally safe, with rates of adverse reactions and serious adverse events similar between CCP recipients and controls. The analysis also showed that the incidence of treatment-related adverse reactions and venous and arterial thrombotic events was comparable between CCP and control groups. The review provides the largest analysis of CCP safety to date and aims to provide definitive answers on its safety. However, it is important to note that most of the included studies were judged to have a high or unclear risk of bias, and the evidence of safety was of low or moderate certainty. [Extracted from the article]

In the quest to produce artificial cells, one key challenge that remains to be solved is the recreation of a complex cellular membrane. Among the existing models, giant unilamellar vesicles (GUVs) are particularly interesting due to their intrinsic compartmentalisation ability and their resemblance in size and shape to eukaryotic cells. Many techniques have been developed to produce GUVs all having inherent advantages and disadvantages. Here, the authors show that fluorinated silica nanoparticles (FNPs) used to form Pickering emulsions in a fluorinated oil can destabilise lipid nanosystems to template the formation of GUVs. This technique enables GUV production across a broad spectrum of buffer conditions, while preventing the leakage of the encapsulated components into the oil phase. Furthermore, a simple centrifugation process is sufficient for the release of the emulsion‐trapped GUVs, bypassing the need to use emulsion‐destabilising chemicals. With fluorescent FNPs and transmission electron microscopy, the authors confirm that FNPs are efficiently removed, producing contaminant‐free GUVs. Further experiments assessing the lateral diffusion of lipids and unilamellarity of the GUVs demonstrate that they are comparable to GUVs produced via electroformation. Finally, the ability of incorporating transmembrane proteins is demonstrated, highlighting the potential of this method for the production of GUVs for artificial cell applications. [ABSTRACT FROM AUTHOR]

This COVID‐19 outpatient randomized controlled trials (RCTs) systematic review compares hospitalization outcomes amongst four treatment classes over pandemic period, geography, variants, and vaccine status. Outpatient RCTs with hospitalization endpoint were identified in Pubmed searches through May 2023, excluding RCTs <30 participants (PROSPERO‐CRD42022369181). Risk of bias was extracted from COVID‐19‐NMA, with odds ratio utilized for pooled comparison. Searches identified 281 studies with 61 published RCTs for 33 diverse interventions analyzed. RCTs were largely unvaccinated cohorts with at least one COVID‐19 hospitalization risk factor. Grouping by class, monoclonal antibodies (mAbs) (OR = 0.31 [95% CI = 0.24−0.40]) had highest hospital reduction efficacy, followed by COVID‐19 convalescent plasma (CCP) (OR = 0.69 [95% CI = 0.53−0.90]), small molecule antivirals (OR = 0.78 [95% CI = 0.48−1.33]), and repurposed drugs (OR = 0.82 [95% CI: 0.72−0.93]). Earlier in disease onset interventions performed better than later. This meta‐analysis allows approximate head‐to‐head comparisons of diverse outpatient interventions. Omicron sublineages (XBB and BQ.1.1) are resistant to mAbs Despite trial heterogeneity, this pooled comparison by intervention class indicated oral antivirals are the preferred outpatient treatment where available, but intravenous interventions from convalescent plasma to remdesivir are also effective and necessary in constrained medical resource settings or for acute and chronic COVID‐19 in the immunocompromised. [ABSTRACT FROM AUTHOR]

Introduction: Progressive multifocal leukoencephalopathy is a rare but often fatal complication of some multiple sclerosis treatments. Although it has mainly been associated with natalizumab treatment, its appearance with other immunosuppressive therapies has also been reported. Aims: The aim of this case report is to describe the development of progressive multifocal encephalopathy in a patient with relapsing–remitting multiple sclerosis treated with ocrelizumab without previous use of natalizumab. Conclusions: A summary of the presentation and disease course is provided, presented in the context of the current literature and likely pathophysiology. [ABSTRACT FROM AUTHOR]

Biohybrid systems can combine inorganic light‐harvesting materials and whole‐cell biocatalysts to utilize solar energy for the production of chemicals and fuels. Whole‐cell biocatalysts have an intrinsic self‐repair ability and are able to produce a wide variety of multicarbon chemicals in a sustainable way with metabolic engineering. Current whole‐cell biohybrid systems have a yet undefined electron transfer pathway between the light‐absorber and metabolic enzymes, limiting rational design. To enable engineering of efficient electron transfer pathways, covalent biohybrids consisting of graphitic nitrogen doped carbon dots (g‐N‐CDs) and the outer‐membrane decaheme protein, MtrC from Shewanella oneidensis MR‐1 are developed. MtrC is a subunit of the MtrCAB protein complex, which provides a direct conduit for bidirectional electron exchange across the bacterial outer membrane. The g‐N‐CDs are functionalized with a maleimide moiety by either carbodiimide chemistry or acyl chloride activation and coupled to a surface‐exposed cysteine of a Y657C MtrC mutant. MtrC∼g‐N‐CD biohybrids are characterized by native and denaturing gel electrophoresis, chromatography, microscopy, and fluorescence lifetime spectroscopy. In the presence of a sacrificial electron donor, visible light irradiation of the MtrC∼g‐N‐CD biohybrids results in reduced MtrC. The biohybrids may find application in photoinduced transmembrane electron transfer in S. oneidensis MR‐1 for chemical synthesis in the future. [ABSTRACT FROM AUTHOR]

There is much human disadvantage and unmet need in the world, including deficits in basic resources and services considered to be human rights, such as drinking water, sanitation and hygiene, healthy nutrition, access to basic healthcare, and a clean environment. Furthermore, there are substantive asymmetries in the distribution of key resources among peoples. These deficits and asymmetries can lead to local and regional crises among peoples competing for limited resources, which, in turn, can become sources of discontent and conflict. Such conflicts have the potential to escalate into regional wars and even lead to global instability. Ergo: in addition to moral and ethical imperatives to level up, to ensure that all peoples have basic resources and services essential for healthy living and to reduce inequalities, all nations have a self‐interest to pursue with determination all available avenues to promote peace through reducing sources of conflicts in the world. Microorganisms and pertinent microbial technologies have unique and exceptional abilities to provide, or contribute to the provision of, basic resources and services that are lacking in many parts of the world, and thereby address key deficits that might constitute sources of conflict. However, the deployment of such technologies to this end is seriously underexploited. Here, we highlight some of the key available and emerging technologies that demand greater consideration and exploitation in endeavours to eliminate unnecessary deprivations, enable healthy lives of all and remove preventable grounds for competition over limited resources that can escalate into conflicts in the world. We exhort central actors: microbiologists, funding agencies and philanthropic organisations, politicians worldwide and international governmental and non‐governmental organisations, to engage – in full partnership – with all relevant stakeholders, to 'weaponise' microbes and microbial technologies to fight resource deficits and asymmetries, in particular among the most vulnerable populations, and thereby create humanitarian conditions more conducive to harmony and peace. [ABSTRACT FROM AUTHOR]

Background: While the use of convalescent plasma (CP) in the ongoing COVID‐19 pandemic has been inconsistent, CP has the potential to reduce excess morbidity and mortality in future pandemics. Given constraints on CP supply, decisions surrounding the allocation of CP must be made. Study Design and Methods: Using a discrete‐time stochastic compartmental model, we simulated implementation of four potential allocation strategies: administering CP to individuals in early hospitalization with COVID‐19; administering CP to individuals in outpatient settings; administering CP to hospitalized individuals and administering any remaining CP to outpatient individuals and administering CP in both settings while prioritizing outpatient individuals. We examined the final size of SARS‐CoV‐2 infections, peak and cumulative hospitalizations, and cumulative deaths under each of the allocation scenarios over a 180‐day period. We compared the cost per weighted health benefit under each strategy. Results: Prioritizing administration to patients in early hospitalization, with remaining plasma administered in outpatient settings, resulted in the highest reduction in mortality, averting on average 15% more COVID‐19 deaths than administering to hospitalized individuals alone (95% CI [11%–18%]). Prioritizing administration to outpatients, with remaining plasma administered to hospitalized individuals, had the highest percentage of hospitalizations averted (22% [21%–23%] higher than administering to hospitalized individuals alone). Discussion: Convalescent plasma allocation strategy should be determined by the relative priority of averting deaths, infections, or hospitalizations. Under conditions considered, mixed allocation strategies (allocating CP to both outpatient and hospitalized individuals) resulted in a larger percentage of infections and deaths averted than administering CP in a single setting. [ABSTRACT FROM AUTHOR]

Background: It is important to maintain the safety of blood products by avoiding the transfusion of units with known and novel viral pathogens. It is unknown whether COVID‐19 convalescent plasma (CCP) may contain pathogenic viruses (either newly acquired or reactivated) that are not routinely screened for by blood centers. Methods: The DNA virome was characterized in potential CCP donors (n = 30) using viral genome specific PCR primers to identify DNA plasma virome members of the Herpesviridae [Epstein Barr Virus (EBV), cytomegalovirus (CMV), human herpesvirus 6A/B, human herpesvirus 7] and Anelloviridae [Torque teno viruses (TTV), Torque teno mini viruses (TTMV), and Torque teno midi viruses (TTMDV)] families. In addition, the RNA plasma virome was characterized using unbiased metagenomic sequencing. Sequencing was done on a HiSeq2500 using high output mode with a read length of 2X100 bp. The sequencing reads were taxonomically classified using Kraken2. CMV and EBV seroprevalence were evaluated using a chemiluminescent immunoassay. Results: TTV and TTMDV were detected in 12 (40%) and 4 (13%) of the 30 study participants, respectively; TTMDV was always associated with infection with TTV. We did not observe TTMV DNAemia. Despite CMV and EBV seroprevalences of 33.3% and 93.3%, respectively, we did not detect Herpesviridae DNA among the study participants. Metagenomic sequencing did not reveal any human RNA viruses in CCP, including no evidence of circulating SARS‐CoV‐2. Discussion: There was no evidence of pathogenic viruses, whether newly acquired or reactivated, in CCP despite the presence of non‐pathogenic Anelloviridae. These results confirm the growing safety data supporting CCP. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N2O) is a potent greenhouse and ozone‐reactive gas for which emissions are growing rapidly due to increasingly intensive agriculture. Synthetic catalysts for N2O decomposition typically contain precious metals and/or operate at elevated temperatures driving a desire for more sustainable alternatives. Here we demonstrate self‐assembly of liposomal microreactors enabling catalytic reduction of N2O to the climate neutral product N2. Photoexcitation of graphitic N‐doped carbon dots delivers electrons to encapsulated N2O Reductase enzymes via a lipid‐soluble biomolecular wire provided by the MtrCAB protein complex. Within the microreactor, electron transfer from MtrCAB to N2O Reductase is facilitated by the general redox mediator methyl viologen. The liposomal microreactors use only earth‐abundant elements to catalyze N2O removal in ambient, aqueous conditions. [ABSTRACT FROM AUTHOR]

The three‐dimensional structure of the enzymes provides very relevant information on the arrangement of the catalytic machinery and structural elements gating the active site pocket. The recent success of the neural network Alphafold2 in predicting the folded structure of proteins from the primary sequence with high levels of accuracy has revolutionized the protein design field. However, the application of Alphafold2 for understanding and engineering function directly from the obtained single static picture is not straightforward. Indeed, understanding enzymatic function requires the exploration of the ensemble of thermally accessible conformations that enzymes adopt in solution. In the present study, we evaluate the potential of Alphafold2 in assessing the effect of the mutations on the conformational landscape of the beta subunit of tryptophan synthase (TrpB). Specifically, we develop a template‐based Alphafold2 approach for estimating the conformational heterogeneity of several TrpB enzymes, which is needed for enhanced stand‐alone activity. Our results show the potential of Alphafold2, especially if combined with molecular dynamics simulations, for elucidating the changes induced by mutation in the conformational landscapes at a rather reduced computational cost, thus revealing its plausible application in computational enzyme design. [ABSTRACT FROM AUTHOR]

Dexamethasone is another inexpensive generic drug that reduces COVID-19 mortality in patients who require oxygen treatment with or without mechanical ventilation.13 It is not effective in those not receiving respiratory support. ACE inhibitors, ARBs, COVID-19, generic drugs, next pandemic, statins, treatment In an earlier study, combination statin/ACE inhibitor treatment was associated with reduced inflammatory biomarkers in patients with coronary artery bypass surgery.20 1 TABLEObservational studies of the reduction in 28-30-day COVID-19 mortality following inhospital statin treatment and statin withdrawal. Keywords: ACE inhibitors; ARBs; COVID-19; generic drugs; next pandemic; statins; treatment EN ACE inhibitors ARBs COVID-19 generic drugs next pandemic statins treatment 1 4 4 08/17/22 20220801 NES 220801 Scientists are concerned about the origins of SARS-CoV-2, which has caused a devastating global pandemic. [Extracted from the article]

Summary: As human activity in space continues to increase, understanding how biological assets respond to spaceflight conditions is becoming more important. Spaceflight conditions include exposure to ionizing radiation, microgravity, spacecraft vibrations and hypervelocity; all of which can affect the viability of biological organisms. Previous studies have shown that melanin‐producing fungi are capable of surviving the vacuum of space and Mars‐simulated conditions in Low Earth Orbit. This survival has been associated in part with the protective effects of melanin, but a comparison of fungal viability in the presence or absence of melanin following spaceflight has never been tested. In this study, we evaluated the protective effects of melanin by comparing the viability of melanized and non‐melanized clones of Cryptococcus neoformans yeasts following a roundtrip to the International Space Station. Yeast colonies were placed inside two MixStix silicone tubes; one stayed on Earth and the other was transported inside for 29 days before returning to Earth. Post‐flight analysis based on colony‐forming unit numbers shows that melanized yeast viability was 50% higher than non‐melanized yeasts, while no difference was observed between the Earth‐bound control samples. The results suggest that fungal melanin could increase the lifespan of biological assets in space. [ABSTRACT FROM AUTHOR]

Viral clearance is likely the best way to assess the efficacy of antibody‐based therapies. Although antibodies can mediate a variety of effects that include modulation of inflammation, the demonstration of viral clearance provides an accessible and measurable parameter that can be used to evaluate efficacy and determine dosing. Therefore, it is important to ascertain the ability of monoclonal antibodies and convalescent plasma to effect viral clearance. For COVID‐19, which is caused by the respiratory virus SARS‐CoV‐2, the most common assay to assess viral clearance is via a nasopharyngeal swab (NPS). However, assessment of antibody efficacy by sampling this site may be misleading because it may not be as accessible to serum antibodies as respiratory secretions or circulating blood. Adding to the complexity of assessing the efficacy of administered antibody, particularly in randomised controlled trials (RCTs) that enroled patients at different times after the onset of COVID‐19 symptoms, viral clearance may also be mediated by endogenous antibody. In this article we critically review available data on viral clearance in RCTs, matched control studies, case series and case reports of antibody therapies in an attempt to identify variables that contribute to antibody efficacy and suggest optimal strategies for future studies. [ABSTRACT FROM AUTHOR]

The synthesis of primary anilines via sustainable methods remains a challenge in organic synthesis. We report a photocatalytic protocol for the selective synthesis of primary anilines via cross‐coupling of a wide range of aryl/heteroaryl halides with sodium azide using a photocatalyst powder consisting of nickel(II) deposited on mesoporous carbon nitride (Ni‐mpg‐CNx). This heterogeneous photocatalyst contains a high surface area with a visible light‐absorbing and adaptive "built‐in" solid‐state ligand for the integrated catalytic Ni site. The method displays a high functional group tolerance, requires mild reaction conditions, and benefits from easy recovery and reuse of the photocatalyst powder. Thereby, it overcomes the need of complex ligand scaffolds required in homogeneous catalysis, precious metals and elevated temperatures/pressures in existing protocols of primary anilines synthesis. The reported heterogeneous Ni‐mpg‐CNx holds potential for applications in the academic and industrial synthesis of anilines and exploration of other photocatalytic transformations. [ABSTRACT FROM AUTHOR]

COVID‐19 convalescent plasma (CCP) was among the few frontline therapies used to treat COVID‐19. After large randomized controlled trials (RCTs) relying on late use in hospitalized patients and/or low antibody titres failed to meet their predefined primary endpoint, the infectious disease community reduced usage of CCP in favour of monoclonal antibodies. Consequently, there are CCP stocks at most transfusion centres worldwide, although scattered usage continues. Further, better designed RCTs are also being launched. The urgent question here is: should we use CCP units collected months before given the largely changed viral variant landscape? We review here in vitro evidence that discourages usage of such CCP units against Delta and other variants of concern. CCP collections should be continued in order to update the armamentarium of therapeutics against vaccine breakthrough infections or in unvaccinated patients and is especially relevant in next‐generation RCTs. [ABSTRACT FROM AUTHOR]

Patients transfused with at least two CCP units (patients nos 1-4 and patients nos 7 and 8) cleared the virus faster (median 21 days vs 32 days) than patients receiving only one CCP unit (patients nos 5 and 6). Keywords: COVID-19 convalescent plasma; immunocompromised; neutralizing antibodies; rituximab EN COVID-19 convalescent plasma immunocompromised neutralizing antibodies rituximab e22 e24 3 01/16/23 20230115 NES 230115 We read with interest the recent paper by Gachoud et al., shedding light on plasma anti-spike immunoglobulin G (IgG) level kinetics in 36 immunocompromised COVID-19 patients (mostly unvaccinated and seronegative) transfused with plasma at the time of the alpha variant of concern (VOC).[1] Seventeen patients received four 200-ml units of convalescent plasma (CP) over 48 h, while 19 patients received two 200-ml units of two-dose mRNA vaccine plasma [either putatively COVID-19-naïve (VP) or COVID-19-experienced (CP/VP, a.k.a. "hybrid" plasma or VaxCCP)] over 24 h. The authors show that, in 17 patients previously treated with anti-CD20 monoclonal antibodies within the last 12 months, who represent a difficult-to-treat COVID-19 patient population, post-transfusion plasma anti-spike IgG levels are lower than in 19 untreated immunocompromised patients. [Extracted from the article]

Immunocompromised patients represent the most problematic cohort of coronavirus disease 2019 (COVID-19) management nowadays, given the inability of most to mount a protective antibody response after vaccination. Current guidelines recommend a repeat dose every 6 months.[1] This makes it impossible to assess a vaccine-elicited endogenous anti-Spike antibody response on the background of Evusheld™. Discriminating endogenous vaccine-elicited anti-Spike antibody responses from exogenous anti-Spike monoclonal antibodies: The case of Evusheld. [Extracted from the article]

In this study, we combine in situ spectroelectrochemistry coupled with electron paramagnetic resonance (EPR) and X‐ray absorption spectroscopies (XAS) to investigate a molecular Ru‐based water oxidation catalyst bearing a polypyridinic backbone [RuII(OH2)(Py2Metacn)]2+. Although high valent key intermediate species arising in catalytic cycles of this family of compounds have remain elusive due to the lack of additional anionic ligands that could potentially stabilize them, mechanistic studies performed on this system proposed a water nucleophilic attack (WNA) mechanism for the O−O bond formation. Employing in situ experimental conditions and complementary spectroscopic techniques allowed to observe intermediates that provide support for a WNA mechanism, including for the first time a Ru(V) oxo intermediate based on the Py2Metacn ligand, in agreement with the previously proposed mechanism. [ABSTRACT FROM AUTHOR]

Decades of studies on antibody structure led to the tenet that the V region binds antigens while the C region interacts with immune effectors. In some antibodies, however, the C region affects affinity and/or specificity for the antigen. One example is the 3E5 monoclonal murine IgG family, in which the mIgG3 isotype has different fine specificity to the Cryptococcus neoformans capsule polysaccharide than the other mIgG isotypes despite their identical variable sequences. Our group serendipitously found another pair of mIgG1/mIgG3 antibodies based on the 2H1 hybridoma to the C. neoformans capsule that recapitulated the differences observed with 3E5. In this work, we report the molecular basis of the constant domain effects on antigen binding using recombinant antibodies. As with 3E5, immunofluorescence experiments show a punctate pattern for 2H1‐mIgG3 and an annular pattern for 2H1‐mIgG1; these binding patterns have been associated with protective efficacy in murine cryptococcosis. Also as observed with 3E5, 2H1‐mIgG3 bound on ELISA to both acetylated and non‐acetylated capsular polysaccharide, whereas 2H1‐mIgG1 only bound well to the acetylated form, consistent with differences in fine specificity. In engineering hybrid mIgG1/mIgG3 antibodies, we found that switching the 2H1‐mIgG3 hinge for its mIgG1 counterpart changed the immunofluorescence pattern to annular, but a 2H1‐mIgG1 antibody with an mIgG3 hinge still had an annular pattern. The hinge is thus necessary but not sufficient for these changes in binding to the antigen. This important role for the constant region in antigen binding could affect antibody biology and engineering. [ABSTRACT FROM AUTHOR]

The functionalization of aryl C(sp2)−H bonds is a useful strategy for the late‐stage modification of biologically active molecules, especially for the regioselective introduction of azole heterocycles to prepare medicinally‐relevant compounds. Herein, we describe a practical photocatalytic transformation using a mesoporous carbon nitride (mpg‐CNx) photocatalyst, which enables the efficient azolation of various arenes through direct oxidation. The method exhibits a broad substrate scope and is amenable to the late‐stage functionalization of several pharmaceuticals. Due to the heterogeneous nature and high photocatalytic stability of mpg‐CNx, the catalyst can be easily recovered and reused leading to greener and more sustainable routes, using either batch or flow processing, to prepare these important compounds of interest in pharmaceutical and agrochemical research. [ABSTRACT FROM AUTHOR]

Predictive biomarkers of trabectedin represent an unmet need in advanced soft‐tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR‐related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six‐gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high‐risk gene signature group showed a significantly worse progression‐free survival compared with patients in the low‐risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy. [ABSTRACT FROM AUTHOR]

Background: Biofilm formation on biotic and abiotic surfaces is finely regulated by genetic factors but also by oxygen concentration, pH, temperature and other environmental factors, already extensively explored for bacterial biofilms. Much less is known about fungal biofilm, that is considered a virulence factor for Candida pathogenic species among the few fungal species able to grow and survive at high temperatures such as 37°C as well as those induced by fever. The resistance to high temperatures coupled with the ability to form biofilm are threatening factors of these fungal species that could severely impact at an epidemiological level. Objectives: In this framework, we decided to study the thermal tolerance of biofilms formed by three medical relevant species such as Candida albicans and two non‐Candida albicans Candida species. Methods: Thirty nosocomial strains were investigated for their ability to adhere and grow in proximity and over body temperature (from 31 to 43°C), mimicking different environmental conditions or severe febrile‐like reactions. Results: Candida sessile cells reacted to different temperatures showing a strain‐specific response. It was observed that the attachment and growth respond differently to the temperature and that mechanism of adhesion has different outputs at high temperature than the growth. Conclusions: This strain‐dependent response is probably instrumental to guarantee the best success to cells for the infection, attachment and growth to occur. These observations reinforce the concept of temperature as a major trigger in the evolution of these species especially in this period of increasing environmental temperatures and excessive domestic heating. [ABSTRACT FROM AUTHOR]

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID‐19), including among patients with innate or acquired immunosuppression. However, the association between COVID‐19‐associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched‐control registry study of 143 COVID‐19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID‐19 patients with immunosuppression. We review clinical features and treatment protocols of COVID‐19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID‐19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune‐deficient and immune‐suppressed patients with COVID‐19 warrants further investigation. [ABSTRACT FROM AUTHOR]

Background and Objectives: ABO blood group may affect risk of SARS‐CoV‐2 infection and/or severity of COVID‐19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS‐CoV‐2 vary by ABO blood group. Materials and Methods: Among eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti‐SARS‐CoV‐2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non‐parametric Kruskal–Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS‐CoV‐2 diagnosis. Results: Of the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti‐spike IgA or anti‐spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1–3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4‐1·0], P = 0·053). Conclusion: Eligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID‐19 severity are needed. [ABSTRACT FROM AUTHOR]

Doege-Potter syndrome is a rare hypoglycemic paraneoplastic disorder. This case describes that severe and symptomatic hypoglycemia can occasionally be due to a rare malignant neoplasm, and the differential diagnosis of malignancy should not be overlooked in this setting. [ABSTRACT FROM AUTHOR]

Ni‐deposited mesoporous graphitic carbon nitride (Ni‐mpg‐CNx) is introduced as an inexpensive, robust, easily synthesizable and recyclable material that functions as an integrated dual photocatalytic system. This material overcomes the need of expensive photosensitizers, organic ligands and additives as well as limitations of catalyst deactivation in the existing photo/Ni dual catalytic cross‐coupling reactions. The dual catalytic Ni‐mpg‐CNx is demonstrated for C–O coupling between aryl halides and aliphatic alcohols under mild condition. The reaction affords the ether product in good‐to‐excellent yields (60–92 %) with broad substrate scope, including heteroaryl and aryl halides bearing electron‐withdrawing, ‐donating and neutral groups. The heterogeneous Ni‐mpg‐CNx can be easily recovered from the reaction mixture and reused over multiple cycles without loss of activity. The findings highlight exciting opportunities for dual catalysis promoted by a fully heterogeneous system. [ABSTRACT FROM AUTHOR]

By early 2021, over 25,000 units of CCP were transfused every week in the United States (US) to patients with COVID-197 under conditions that varied in regard to the patient's disease severity, timing of the transfusion, and the number of units transfused. Keywords: blood center operations; FFP transfusion; transfusion practices (adult) EN blood center operations FFP transfusion transfusion practices (adult) 1313 1323 11 04/10/21 20210401 NES 210401 INTRODUCTION Convalescent plasma (CP) has been used as passive immunotherapy for the prevention and treatment of infectious diseases for more than 100 years.1,2 The lack of proven therapies during the early months of the COVID-19 pandemic, a favorable safety profile3,4 and early evidence for efficacy in adults5,6 led to the widespread use of CCP. In addition, there are specific patient populations who could possibly benefit, including pediatric patients, pregnant women, immunosuppressed patients, and other populations at high risk for development of severe or critical COVID-19 disease. As COVID cases surge, the supply of CCP has been outstripped by demand, resulting in the need for more thoughtful use so that transfusions are limited to patients for whom CCP is likely to be effective. [Extracted from the article]

Among the thermophilic fishes that have become established in the north‐western Mediterranean as a consequence of sea warming, the yellowmouth barracuda (Sphyraena viridensis Cuvier, 1829) appears to be one of the most successful and abundant in the coastal rocky environment, having increasingly become the object of recreational and commercial exploitation in the study area. Lure‐fishing sessions were carried out from May 2016 to November 2018 in the Catalan Sea (NE Spain) at dawn and dusk, with the aim of providing new insight into the behavioural, spatial and feeding ecology and vulnerability to angling of this poorly known species. Generalized mixed‐effects linear models showed that S. viridensis is a crepuscular inshore dweller, whose vulnerability to angling is significantly influenced by solar and lunar light intensities, being highest in the pre‐spawn and spawning periods. Asymmetries between dawn and dusk activity patterns were detected, evidently related to a drop in aggressiveness at dusk following the spawning period. The simple study design adopted may be applied to other contexts, aiming to the recognition of several levels of fish vulnerability to angling. [ABSTRACT FROM AUTHOR]

The intracellular pathogen concept classifies pathogenic microbes on the basis of their site of replication and dependence on host cells. This concept played a fundamental role in establishing the field of cellular microbiology, founded in part by Dr. Pascale Cossart, whose seminal contributions are honored in this issue of Molecular Microbiology. The recognition that microbes can access and replicate in privileged compartments within host cells has led to many new and fruitful lines of investigation into the biology of the cell and mechanisms of cell‐mediated immunity. However, like any scientific concept, the intracellular pathogen concept can become a dogma that constrains thinking and oversimplifies complex and dynamic host–pathogen interactions. Growing evidence has blurred the distinction between "intracellular" and "extracellular" pathogens and demonstrated that many pathogens can exist both within and outside of cells. Although the intracellular pathogen concept remains useful, it should not be viewed as a rigid classification of pathogenic microbes, which exhibit remarkable variation and complexity in their behavior in the host. [ABSTRACT FROM AUTHOR]

COVID-19 convalescent plasma for the treatment of immunocompromised patients: a systematic review. medRxiv. 2021. https://doi.org/10.1101/2021.12.24.21268317 10 Focosi D, Tuccori M. Prescription of anti-spike monoclonal antibodies in COVID-19 patients with resistant SARS-CoV-2 variants in Italy. Keywords: convalescent plasma; COVID-19; oncohematology; SARS-CoV-2 EN convalescent plasma COVID-19 oncohematology SARS-CoV-2 208 209 2 02/03/23 20230201 NES 230201 DATA AVAILABILITY STATEMENT Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. [Extracted from the article]

Summary: The biological functions of fungal extracellular vesicles (EVs) or exosomes have been mostly determined on the basis of the assumption that they are vehicles of trans‐cell wall transport and molecular export. The possibility that fungal cells can bind to and internalize EVs remained largely unaddressed. Recent studies, however, demonstrated that fungal cells can internalize host‐derived and/or fungal EVs through processes that profoundly modify their regular physiology. To illustrate this novel view, we discuss (i) the uptake of plant EVs by phytopathogenic fungi culminating in growth defects and virulence attenuation, (ii) the influence of EV internalization in prion transmission and biofilm formation in yeast cells, and (iii) the EV‐mediated transfer of virulence in isolates of Cryptococcus gattii. These recent observations indicate that the functions exerted by EVs in fungal cells result from previously unknown mechanisms of bidirectional transport, opening new venues for the investigation of how EVs impact fungal physiology. The traffic of extracellular vesicles in fungal cells is bidirectional. It has been known for a decade that fungal cells can package molecules inside vesicles for further extracellular release. Recent studies, however, have demonstrated that fungal cells can also internalize extracellular vesicles through processes that result in fundamental biological responses. [ABSTRACT FROM AUTHOR]

Abstract: The conformational landscape of Bacillus megaterium epoxide hydrolase (BmEH) and how it is altered by mutations that confer the enzyme the ability to accept bulky epoxide substrates has been investigated. Extensive molecular dynamics (MD) simulations coupled to active site volume calculations have unveiled relevant features of the enzyme conformational dynamics and function. Our long‐timescale MD simulations identify key conformational states not previously observed by means of X‐ray crystallography and short MD simulations that present the loop containing one of the catalytic residues, Asp239, in a wide‐open conformation, which is likely involved in the binding of the epoxide substrate. Introduction of mutations M145S and F128A dramatically alters the conformational landscape of the enzyme. These singly mutated variants can accept bulky epoxide substrates due to the disorder induced by mutation in the α‐helix containing the catalytic Tyr144 and some parts of the lid domain. These changes impact the enzyme active site, which is substantially wider and more complementary to the bulky pharmacologically relevant epoxide substrates. [ABSTRACT FROM AUTHOR]

Aims CD274 ( PDL1) and JAK2 (9p24.1) gene amplifications have been recently described in pulmonary carcinomas in association with programmed death-ligand 1 ( PD-L1) expression. Furthermore, PTEN loss has been explored preclinically in relation to PD-L1 expression. Our aim was to determine whether these genomic alterations affect PD-L1 expression levels in non-small-cell lung cancer. Methods and results PD-L1 and PTEN expression determined by immunohistochemistry ( IHC), and CD274, JAK2 and PTEN copy number alterations ( CNAs) determined by fluorescence in-situ hybridisation, were studied in 171 pulmonary carcinoma specimens. PD-L1 expression was positive in 40 cases (23.3%), and CD274 amplification was present in 14 tumours (8.8%). Concordance between both events was found in 12 of 14 amplified cases ( P = 0.0001). We found nine JAK2-amplified cases (5.7%), seven with PD-L1 expression ( P = 0.0006). Moreover, six of the seven cases had JAK2 and CD274 coamplification (9p24.1 genomic amplification). Remarkably, the average PD-L1 IHC score was higher in these amplified cases (230 versus 80; P = 0.001). Non-statistical associations were observed between PD-L1 expression and PTEN loss and PTEN deletions. Conclusions We describe a subset of patients (8.2%) who had 9p24.1 amplifications resulting in high expression of PD-L1. Our results provide evidence for genomic up-regulation of PD-L1 expression in non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Pathogen reduction technologies need to evaluate Fc-mediated antibody functions Hence, we urge all PRT suppliers to test the phagocytic, complement activating, and ADCC function of antibodies before and after PRT to ascertain the effect of any of these methods. We read with interest the recent article by Bagri et al reporting no detrimental effects of Intercept® on anti-SARS-CoV-2 antibodies in COVID-19 convalescent plasma (CCP) in terms of antigen binding, neutralizing, and epitope microarrays.1 We commend the investigators for the careful work done in their study. [Extracted from the article]

Microbial melanins provide a biocompatible and scalable approach for bioremediation and radioprotection technologies due to their physicochemical properties. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) infection is considered a necessary step for the development of cervical cancer, and >95% of all cervical cancers have detectable HPV sequences. The authors of this report recently demonstrated the efficacy of radioimmunotherapy (RIT) targeting viral oncoprotein E6 in the treatment of experimental cervical cancer. They hypothesized that the pretreatment of tumor cells with various agents that cause cell death and/or elevation of E6 levels would increase the accumulation of radiolabeled antibodies to E6 in cervical tumors.Methods: HPV type 16 (HPV-16)-positive CasKi cells were treated in vitro with up to 6 grays of external radiation, or with the proteasome inhibitor MG-132, or with unlabeled anti-E6 antibody C1P5; and cell death was assessed. The biodistribution of (188)Re-labeled C1P5 antibody was determined in both control and radiation MG-132-treated CasKi tumor-bearing nude mice.Results: (188)Re-C1P5 antibody demonstrated tumor specificity, very low uptake, and fast clearance from the major organs. The amount of tumor uptake was enhanced by MG-132 but was unaffected by pretreatment with radiation. In addition, in vitro studies demonstrated an unanticipated effect of unlabeled antibody on the amount of cell death, a finding that was suggested by the authors' previous in vivo studies in a CasKi tumor model.Conclusions: The current results indicated that pretreatment of cervical tumors with the proteasome inhibitor MG-132 and with unlabeled antibody to E6 can serve as a means to generate nonviable cancer cells and to elevate the levels of target oncoproteins in the cells for increasing the accumulation of targeted radiolabeled antibodies in tumors. These results favor the further development of RIT for cervical cancers targeting viral antigens. [ABSTRACT FROM AUTHOR]

A new family of ruthenium complexes based on the N-pentadentate ligand Py2 Metacn (N-methyl-N',N''-bis(2-picolyl)-1,4,7-triazacyclononane) has been synthesised and its catalytic activity has been studied in the water-oxidation (WO) reaction. We have used chemical oxidants (ceric ammonium nitrate and NaIO4) to generate the WO intermediates [RuII(OH2)(Py2 Metacn)]2+, [RuIII(OH²)(Py2 Metacn)]3+, [RuIII(OH)(Py2 Metacn)]2+ and [RuIV(O)(Py2 Metacn)]2+, which have been characterised spectroscopically. Their relative redox and pH stability in water has been studied by using UV/Vis and NMR spectroscopies, HRMS and spectroelectrochemistry. [RuIV(O)(Py2 Metacn)]2+ has a long half-life (>48 h) in water. The catalytic cycle of WO has been elucidated by using kinetic, spectroscopic, 18O-labelling and theoretical studies, and the conclusion is that the rate-determining step is a single-site water nucleophilic attack on a metal-oxo species. Moreover, [RuIV(O)(Py2 Metacn)]2+ is proposed to be the resting state under catalytic conditions. By monitoring CeIV consumption, we found that the O2 evolution rate is redoxcontrolled and independent of the initial concentration of CeIV. Based on these facts, we propose herein that [RuIV(O)(Py2 Metacn)]2+ is oxidised to [RuV(O)(Py2 Metacn)]2+ prior to attack by a water molecule to give [RuIII(OOH)(Py2 Metacn)]2+. Finally, it is shown that the difference in WO reactivity between the homologous iron and ruthenium [M(OH2)(Py2 Metacn)]2+ (M=Ru, Fe) complexes is due to the difference in the redox stability of the key MV(O) intermediate. These results contribute to a better understanding of the WO mechanism and the differences between iron and ruthenium complexes in WO reactions. [ABSTRACT FROM AUTHOR]

Oxide-derived copper (OD-Cu) electrodes exhibit unprecedented CO reduction performance towards liquid fuels, producing ethanol and acetate with >50 % Faradaic efficiency at −0.3 V (vs. RHE). By using static headspace-gas chromatography for liquid phase analysis, we identify acetaldehyde as a minor product and key intermediate in the electroreduction of CO to ethanol on OD-Cu electrodes. Acetaldehyde is produced with a Faradaic efficiency of ≈5 % at −0.33 V (vs. RHE). We show that acetaldehyde forms at low steady-state concentrations, and that free acetaldehyde is difficult to detect in alkaline solutions using NMR spectroscopy, requiring alternative methods for detection and quantification. Our results represent an important step towards understanding the CO reduction mechanism on OD-Cu electrodes. [ABSTRACT FROM AUTHOR]

In maize (Zea mays), as well as in other crops, transposable elements (TEs) constitute a great proportion of the genome. Chromatin modifications play a vital role in establishing transposon silencing and perpetuating the acquired repressive state. Nucleosomes associated with TEs are enriched for dimethylation of histone H3 at lysine 9 and 27 (H3K9me2 and H3K27me2, respectively), signals of repressive chromatin. Here, we describe a chromatin protein, ZmMBD101, involved in the regulation ofMutator (Mu) genes in maize. ZmMBD101 is localized to the nucleus and contains a methyl-CpG-binding domain (MBD) and a zinc finger CW (CW) domain. Transgenic lines with reduced levels of ZmMBD101 transcript present enhanced induction of Mu genes when plants are irradiated with UV-B. Chromatin immunoprecipitation analysis with H3K9me2 and H3K27me2 antibodies indicated that ZmMBD101 is required to maintain the levels of these histone repressive marks at Muterminal inverted repeats (TIRs) under UV-B conditions. Although Mutator inactivity is associated with DNA methylation, cytosine methylation at Mu TIRs is not affected in ZmMBD101 deficient plants. Several plant proteins are predicted to share the simple CW-MBDdomain architecture present in ZmMBD101. We hypothesize that plant CW-MBDproteins may alsofunction to protect plant genomes from deleterious transposition. [ABSTRACT FROM AUTHOR]

Oculomasticatory myorhythmia (OMM) is a hyperkinetic movement disorder, considered a rhythmic form of segmental myoclonus,1 consisting of repetitive, rhythmic and synchronous contractions of ocular and oromandibular muscles. Oculomasticatory Myorhythmia, an Underrecognized Yet Key Finding for the Topographic and Etiological Diagnosis in Patients with Rhombencephalitis. Final diagnosis was rhombencephalitis secondary to WD. Intravenous ampicillin (2 g/4 hours) treatment was completed for 4 weeks, with progressive motor improvement (being able to walk with a walker) and OMM resolution, persisting 20 months later. [Extracted from the article]

The structural and elemental configuration of a high-performing Pd-Hg electrocatalyst for oxygen reduction to hydrogen peroxide has been studied by means of high-resolution scanning transmission electron microscopy. Pd-Hg nanoparticles are shown to have a crystalline core-shell structure, with a Pd core and a Pd-Hg ordered alloy shell. The ordered shell is responsible for the high oxygen reduction selectivity to H2O2. [ABSTRACT FROM AUTHOR]

The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic's endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. [ABSTRACT FROM AUTHOR]

Aim Predicting the impact of climate change on marine ecosystems or how fish and other species are adapting to rising sea temperatures is still subject to much uncertainty, despite considerable progress in recent years. In this study we assess whether our understanding of the impact of sea warming on marine fish can be enhanced with an interdisciplinary approach that collates data from fisheries, fishermen and scientific research. By doing this, we aim to shed light on the major changes in the abundance and diversity of warm and cold water fish in recent decades in relation to sea warming. Location This study was conducted in the north-western Mediterranean, where the impacts of global warming are particularly critical because range shifts are physically constrained. Methods We collected and combined statistical data from fisheries, the traditional ecological knowledge of fishermen ( TEK), reproductive data (histological gonad analyses and ichthyoplankton surveys) and extensive research into the relevant literature (including systematic catalogues and museum collections and their databases). Results We have found that changes in the abundance of fish have followed a particular spatio-temporal sequence, with three different phases of colonization in the case of warm-water species (occasional occurrence, common presence and establishment), and three phases of regression (abundance reduction, range contraction and disappearance from the catch) in the case of cold-water species. Main conclusions Overall, the results show that this multidisciplinary approach, combining qualitative and quantitative information from different sources, provides new insight into the observed changes in fish diversity and abundance in relation to climate change. [ABSTRACT FROM AUTHOR]