bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of delay on culture of urine
Authors: Hindman R , Tronic B , Bartlett R
Published: June 2021

One hundred random urine specimens which were submitted for culture were planted using a calibrated loop within 2 h of collection and 2 and 4 h later after standing at room temperature. Colonies were counted after an 18- to 24-h incubation at 37 degrees C. Fifteen of the specimens demonstrated increases in counts exceeding 1 X log10; four increased from less than 10(5)/ml to greater than 10(5)/ml (three by the 4-h culture and a fourth by the 6-h culture), supporting the concept that delays of greater than 2 h in inoculating cultures may produce results which could cause errors in diagnosis.
Plaque reduction neutralization test for human cytomegalovirus based upon enhanced uptake of neutral red by virus-infected cells
Authors: Schmidt N J , Dennis J , Lennette E H
Published: June 2021

Foci of cells infected with human cytomegalovirus were noted to stain more intensely than uninfected cells with neutral red, and this provided the basis for development of a plaque assay and plaque reduction neutralization test for cytomegalovirus. Plaques demonstrable by neutral red staining could be counted at 8 days after infection; thus, results could be obtained earlier than for plaque assay systems based upon the viral cytopathic effect, a fewer manipulations were required for staining cell monolayers to demonstrate plaques. Certain variables affecting plaque size and numbers and antibody titers were defined. Addition of fresh guinea pig complement to the reaction mixtures markedly enhanced cytomegalovirus-neutralizing antibody titers of hyperimmune animal sera, but titers of human sera were enhanced only two-or fourfold.
Isolation and characterization of a bacteriophage specific for Neisseria perflava
Authors: Steinberg V I , Hart E J , Handley J , Goldberg I D
Published: June 2021

Six isolates from normal throat samples have been shown to contain phage active against Neisseria perflava. The phage isolates were similar in terms of host range, latent period, burst size, antigenic properties, morphology, and nucleic acid content. Neutralization studies with antisera demonstrated that the isolates exhibited a very high degree of serological relatedness. These results taken together suggested that the isolates represented a single strain of bacteriophage. This phage, which we have designated NP-1, exhibited a high degree of host specificity, attacking only one of the several strains of N. perflava tested and none of the other species tested. One-step growth experiments yielded minimum latent periods of approximately 35 min; average burst sizes varied from 34 to 63 plaque-forming units per cell. Electron micrographs revealed particles with heads averaging 75 nm in diameter and tails averaging 300 nm in length and 18 nm in diameter. The phage contained double-stranded DNA with a guanine plus cytosine content of 38%.
Solid-phase radioimmunoassay of rubella virus immunoglobulin G and immunoglobulin M antibodies
Authors: Kalimo K O , Meurman O H , Halonen P E , Ziola B R , Viljanen M K , Granfors K , Toivanen P
Published: June 2021

A solid-phase radioimmunoassay method has been developed for the detection of rubella virus-specific immunoglobulin G (IgG) and IgM antibodies in human serum specimens. Purified rubella virus was adsorbed onto polystyrene balls, and antibodies that attached to the virus-treated balls were detected by subsequent binding of 125I-labeled anti-human gamma or anti-human mu immunoglobulins. A total of 77 serum specimens were tested. Binding ratios between positive and negative sera were as high as 22 in the IgG assay but rarely exceeded 3 in the IgM assay. The sensitivity of the IgG assay was found to be 16 to 256 times higher than that of the rubella virus hemagglutination inhibition test. The IgG radioimmunoassay can be readily adopted for routine diagnostic use. The IgM radioimmunoassay, however, due to its lower sensitivity, must be modified before being routinely applied.
Preparation of typing antisera specific for O antigens of Pseudomonas aeruginosa
Authors: Duncan N H , Hinton N A , Penner J L , Duncan I B
Published: June 2021

Results of serotyping 966 clinical isolates of Pseudomonas aeruginosa showed that 72% agglutinated specifically in one or another of the 16 typing antisera, but 28% agglutinated in two or more and often in as many as 10 antisera; this polyagglutinability correlated with a high incidence of cross-reactivity among the antisera. Absorption of each typing antiserum with either cell suspensions of five O-type strains or with a suspension of a particular polyagglutinable strain (SMC 247) abolished cross-reactivity in the typing antisera without significantly reducing titers against the homologous strains. All but four of the polyagglutinable strains agglutinated specifically in one or another absorbed antisera. The cross-reactions of unabsorbed antisera were interpreted to have been caused by antibodies directed not against specific O antigens but against thermostable specificities that remain undefined.
Evaluation of reagin screen, a new serological test for syphilis
Authors: Dyckman J D , Wende R D , Gantenbein D , Williams R P
Published: June 2021

A total of 1,020 serum and plasma specimens were tested using the Venereal Disease Research Laboratory (VDRL), Rapid Plasma Reagin (RPR) card, Reagin Screen (RST) and Fluorescent Treponemal Antibody-Absorption (FTA-ABS) tests. In 257 normal patients, all screening tests were nonreactive; the FTA-ABS test was reactive for one patient. In 588 patients with treated and untreated syphilis, the RST results were 91.7% in agreement with the VDRL and RPR results. In 175 patients with diseases that cause biological false reactions, the RST was 94% in agreement with the other screening tests. The titer of the RST was within one dilution of the corresponding VDRL titer in 91.7% of the 360 speciments tested and within one dilution of the RPR titer in 96.9% of 358 specimens quantitated by both tests.
Application of freeze-dried, one-day-old chick erythrocytes to viral hemagglutination and hemagglutination-inhibition tests
Authors: Ito H , Iwasa S
Published: June 2021

Erythrocytes collected from 1-day-old chicks were stabilized by fixation with formaldehyde and by freeze-drying after treatment with carbon monoxide. Suspensions of freeze-dried erythrocytes in distilled water or physiological saline had a homogeneous bright reddish-purple color. Freeze-dried erythrocytes were compared with fresh erythrocytes for hemagglutination and hemagglutination-inhibition tests for various viruses including rubella, Japanese encephalitis, influenza, mumps, Newcastle disease, and Sendai viruses. After storage at 4 degrees C for 1 year or more, freeze-dried erythrocytes maintained their original appearance and sensitivity to hemagglutination antigens.
SXT and Taxo A Disks for Presumptive Identification of Group A and B Streptococci in Throat Cultures
Authors: Gunn Bruce A.
Published: June 2021

A bacitracin (0.04 units, BBL)-SXT (trimethoprim, 1.25 mg, plus sulfamethoxazole, 23.75 mg, BBL) susceptibility test was 94% accurate in presumptively identifying streptococci as either group A, B or not group A and B.
Characterization of bacteroides melaninogenicus
Authors: Harding G K , Sutter V L , Finegold S M , Bricknell K S
Published: June 2021

Fifty-eight human isolates of Bacteroides melaninogenicus, 42 from a variety of clinical infections and the rest from normal flora, were studied for pigment production and ultraviolet light fluorescence and by forty biochemical and other tests, including end-product analysis by gas-liquid chromatography. In a number of instances, tests were repeated several times and the results were reproducible. Agar plate dilution susceptibility tests were also performed to 12 antimicrobial agents. These 58 strains could be reliably placed into three groups, corresponding to the three subspecies described, based on seven characteristics. These included acid production in peptone-yeast-glucose medium, production of n-butyric acid from peptone-yeast-glucose medium, esculin hydrolysis, starch hydrolysis, indole production, effect on milk, and lipase production. Production of hydrogen gas in peptone-yeast-fructose medium may be another distinguishing characteristic. In general there was not much difference in the susceptibility of the three groups to the various antimicrobial agents tested. Two strains had a minimal inhibitory concentration of penicillin G of 16 and 32 U/ml, respectively. Three strains did not produce a black pigment in spite of prolonged incubation on blood-containing media.
Antagonistic action of Streptococcus salivarius and Streptococcus faecalis to Mycobacterium tuberculosis
Authors: Darling C L , Hart G D
Published: June 2021

Streptococcus salivarius and Streptococcus faecalis were found to inhibit the growth of Mycobacterium tuberculosis on Löwenstein-Jensen and Middlebrook 7H11 agars, but not on the latter medium when antibacterial drugs were added. S. faecalis was found to be more inhibitory than S. salivarius to 15 strains of M. tuberculosis. S. salivarius produced little or no inhibition of growth of Runyon group III organisms but was very antagonistic to Runyon group I mycobacteria.
Meningitis Due to
Haemophilus influenzae
Type e
Authors: Buck Larry L. , Douglas George W.
Published: June 2021

Haemophilus influenzae
type e was isolated from the cerebrospinal fluid and blood of an 8-month-old child with meningitis.
Effect of chilling on the survival of Bacteroides fragilis
Authors: Hagen J C , Wood W S , Hashimoto T
Published: June 2021

Factors affecting the susceptibility of Bacteroides fragilis subsp. fragilis to low temperature were examined. Predetermined numbers of cells were spread on agar media or suspended in enriched Trypticase soy broth and exposed to low temperature under both aerobic and anaerobic conditions. Exposure of 18-h growth of a freshly isolated B. fragilis strain to 4 degrees C aerobically or anaerobically resulted in a loss of at least 50% viability after 12 h. B. fragilis cells in early growth (6 h) were more tolerant to exposure at 4 degrees C than older cells (18 h). When the freshly isolated strain was repeatedly subcultured in the laboratory it was uniformly more cold tolerant than fresh clinical isolates. The incorporation of 1.0 M sucrose and 5 mM magnesium chloride into liquid media partially alleviated the lethal effects of cold temperature on B. fragilis subsp. fragilis.
Fluorescent pseudomonads capable of growth at 41 degrees C but distinct from Pseudomonas aeruginosa
Authors: Ajello G W , Hoadley A W
Published: June 2021

One hundred and twenty-seven apyocyanogenic fluorescent Pseudomonas strains capable of growth at 41 degrees C, but differing from Pseudomonas aeruginosa, were typed serologically and tested for pyocin production, antibiotic susceptibility, selected biochemical reactions, and utilization of selected substrates. Results were compared with those from 40 apyocyanogenic and 14 pyocyanin-producing strains of P. aeruginosa. Unidentified fluorescent Pseudomonas (UFP) strains generally were not agglutinated by P. aeruginosa antisera and showed little or no pyocin activity. In contrast to P. aeruginosa strains, UFP strains usually failed to oxidize D-gluconate or reduce nitrate to nitrogen gas. They could not use D-gluconate or D-mannitol as sole carbon source and were susceptible to kanamycin. The cellular fatty acid compositions of major UFP groups resembled those of the alcaligenes-stutzeri groups.
Sensitivity of a radioimmunoassay method for detection of certain viral antibodies in sera and cerebrospinal fluids
Authors: Forghani B , Schmidt N J , Lennette E H
Published: June 2021

An indirect solid-phase radioimmunoassay (RIA) was applied to titration of serum and cerebrospinal fluid (CSF) antibodies against a variety of viruses including rubella, mumps, measles, herpes simplex, varicella-zoster, and vaccinia. The test used fixed, virus-infected cells as a source of antigen, and conditions for optimal production of viral antigen were determined for each virus-host cell system. In acute, uncomplicated viral infections, sera taken 2 to 5 days after onset generally had low homotypic RIA titers ranging from less than 1:100 to 1:500, whereas convalescent-phase titers ranged from 1:128,000 to 1:512,000. Rubella and measles antibody titers as high as 1:256,000 were demonstrated by RIA in CSF from patients with chronic panencephalitis, whereas homologous antibody titers of 1:4,000 were detected in CSF from acute mumps, herpes simplex, and varicella-zoster virus infections with central nervous system involvement. Some heterotypic antibody was demonstrable by RIA in CSF, but, with the exception of herpes simplex antibody in a mumps virus infection, titers were markedly lower than those to the infecting virus type. RIA generally demonstrated titers at least 1,000 times higher than those obtained by conventional assays such as complement fixation, hemagglutination inhibition, neutralization, and immunofluorescent staining.
Identification of an Intramolecular Switch That Controls the Interaction of Helicase nsp10 with Membrane-Associated nsp12 of Porcine Reproductive and Respiratory Syndrome Virus
Authors: Hu Yunhao , Ke Purui , Gao Peng , Zhang Yongning , Zhou Lei , Ge Xinna , Guo Xin , Han Jun , Yang Hanchun
Published: June 2021

Assembly of replication and transcription complexes (RTC) is a limiting step for viral RNA synthesis. The PRRSV RTC macromolecular complexes are comprised of mainly viral nonstructural replicase proteins (nsps), but how they come together remains elusive.
African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques
Authors: Crooks Chelsea M. , Weiler Andrea M. , Rybarczyk Sierra L. , Bliss Mason , Jaeger Anna S. , Murphy Megan E. , Simmons Heather A. , Mejia Andres , Fritsch Michael K. , Hayes Jennifer M. , Eickhoff Jens C. , Mitzey Ann M. , Razo Elaina , Braun Katarina M. , Brown Elizabeth A. , Yamamoto Keisuke , Shepherd Phoenix M. , Possell Amber , Weaver Kara , Antony Kathleen M. , Morgan Terry K. , Zeng Xiankun , Dudley Dawn M. , Peterson Eric , Schultz-Darken Nancy , O’Connor David H. , Mohr Emma L. , Golos Thaddeus G. , Aliota Matthew T. , Friedrich Thomas C.
Published: June 2021

ZIKV was first identified in 1947 in Africa, but most of our knowledge of ZIKV is based on studies of the distinct Asian genetic lineage, which caused the outbreak in the Americas in 2015 to 2016. In its most recent update, the WHO stated that improved understanding of African-lineage ZIKV pathogenesis during pregnancy must be a priority.
Large Clostridial Toxins: Mechanisms and Roles in Disease
Authors: Orrell Kathleen E. , Melnyk Roman A.
Published: June 2021

Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family includeClostridioides difficiletoxins TcdA and TcdB,Paeniclostridium sordelliitoxins TcsL and TcsH,Clostridium novyitoxin TcnA, andClostridium perfringenstoxin TpeL.
Macrophages in resistance to candidiasis
Authors: Vázquez-Torres A , Balish E
Published: June 2021

Candida albicans, an increasingly common opportunistic pathogenic fungus, frequently causes disease in immunodeficient but not immunocompetent hosts. Clarifying the role of the phagocytic cells that participate in resistance to candidiasis not only is basic to understanding how the host copes with this dimorphic pathogen but also will expedite the development of innovative prophylactic and therapeutic approaches for treating the multiple clinical presentations that candidiasis encompasses. In this review, we present evidence that a diverse population of mononuclear phagocytes, in different states of activation and differentiation and from a variety of host species, can phagocytize C. albicans blastoconidia via an array of opsonic and nonopsonic mechanisms and can kill C. albicans blastoconidia and hyphae by means of oxygen-dependent and -independent mechanisms. Reactive nitrogen intermediates should now be added to the well-established candidacidal reactive oxygen intermediates of macrophages. Furthermore, what were thought to be two independent pathways, i.e., nitric oxide and superoxide anion, have now been shown to combine to form a potent macrophage candidacidal molecule, peroxynitrite. In contrast to monocytes and neutrophils, which are important in resistance to early stages of C. albicans infections, more differentiated macrophages activated by cytokines such as gamma interferon participate in the acquired resistance of hosts with C. albicans-specific, cell-mediated immunity. Evidence presented in this review demonstrates that mononuclear phagocytes, in some instances in the absence of other professional phagocytes such as neutrophils, play an import role in resistance to systemic and mucosal candidiasis.
Mechanisms of Giardia lamblia differentiation into cysts
Authors: Luján H D , Mowatt M R , Nash T E
Published: June 2021

Microbiologists have long been intrigued by the ability of parasitic organisms to adapt to changes in the environment. Since most parasites occupy several niches during their journey between vectors and hosts, they have developed adaptive responses which allow them to survive under adverse conditions. Therefore, the life cycles of protozoan and helminthic parasites are excellent models with which to study numerous mechanisms involved in cell differentiation, such as the regulation of gene expression, signal transduction pathways, and organelle biogenesis. Unfortunately, many of these studies are very difficult because the conditions needed to elicit developmental changes in parasites remain undetermined in most cases. Recently, several interesting findings were reported on the process of differentiation of Giardia lamblia trophozoites into cysts. G. lamblia is a flagellated protozoan that inhabits the upper small intestine of its vertebrate host and is a major cause of enteric disease worldwide. It belongs to the earliest identified lineage among eukaryotes and therefore offers a unique insight into the progression from primitive to more complex eukaryotic cells. The discovery of a specific stimulus that induces trophozoites to differentiate into cysts, the identification and characterization of encystation-specific molecules, the elucidation of novel biochemical pathways, and the development of useful reagents and techniques have made this parasite an excellent model with which to study differentiation in eukaryotic cells. In this review, we summarize the most recent fundings on several aspects of Giardia differentiation and discuss the significance of these findings within the context of current knowledge in the field.
Rolling-circle replication of bacterial plasmids
Authors: Khan S A
Published: June 2021

Many bacterial plasmids replicate by a rolling-circle (RC) mechanism. Their replication properties have many similarities to as well as significant differences from those of single-stranded DNA (ssDNA) coliphages, which also replicate by an RC mechanism. Studies on a large number of RC plasmids have revealed that they fall into several families based on homology in their initiator proteins and leading-strand origins. The leading-strand origins contain distinct sequences that are required for binding and nicking by the Rep proteins. Leading-strand origins also contain domains that are required for the initiation and termination of replication. RC plasmids generate ssDNA intermediates during replication, since their lagging-strand synthesis does not usually initiate until the leading strand has been almost fully synthesized. The leading- and lagging-strand origins are distinct, and the displaced leading-strand DNA is converted to the double-stranded form by using solely the host proteins. The Rep proteins encoded by RC plasmids contain specific domains that are involved in their origin binding and nicking activities. The replication and copy number of RC plasmids, in general, are regulated at the level of synthesis of their Rep proteins, which are usually rate limiting for replication. Some RC Rep proteins are known to be inactivated after supporting one round of replication. A number of in vitro replication systems have been developed for RC plasmids and have provided insight into the mechanism of plasmid RC replication.
Whole-Genome Sequencing and
De Novo
Assembly of Malassezia pachydermatis Isolated from the Ear Canal of a Dog with Otitis
Authors: D’Andreano S. , Viñes J. , Francino O.
Published: June 2021

We have
de novo
assembled the genome sequence of
Malassezia pachydermatis
isolated from a canine otitis sample with Nanopore-only long reads. With 99× coverage and 8.23 Mbp, the genome sequence was assembled in 10 contigs, with 6 of them corresponding to chromosomes, improving the scaffolding of previous genome assemblies for the species.
Progradational slope architecture and sediment distribution in outcrops of the mixed carbonate-siliciclastic Bone Spring Formation, Permian Basin, west Texas
Authors: Walker Wylie , Jobe Zane R. , Sarg J.F. , Wood Lesli
Published: June 2021

Sediment transport and distribution are the keys to understanding slope-building processes in mixed carbonate-siliciclastic sediment routing systems. The Permian Bone Spring Formation, Delaware Basin, west Texas, is such a mixed system and has been extensively studied in its distal (basinal) extent but is poorly constrained in its proximal upper-slope segment. Here, we define the stratigraphic architecture of proximal outcrops in Guadalupe Mountains National Park in order to delineate the shelf-slope dynamics of carbonate and siliciclastic sediment distribution and delivery to the basin. Upper-slope deposits are predominantly fine-grained carbonate lithologies, interbedded at various scales with terrigenous (i.e., siliciclastic and clay) hemipelagic and gravity-flow deposits. We identify ten slope-building clinothems varying from terrigenous-rich to carbonate-rich and truncated by slope detachment surfaces that record large-scale mass wasting of the shelf margin. X-ray fluorescence (XRF) data indicate that slope detachment surfaces contain elevated proportions of terrigenous sediment, suggesting that failure is triggered by changes in accommodation or sediment supply at the shelf margin. A well-exposed terrigenous-rich clinothem, identified here as the 1st Bone Spring Sand, provides evidence that carbonate and terrigenous sediments were deposited contemporaneously, suggesting that both autogenic and allogenic processes influenced sediment accumulation. The mixing of lithologies at multiple scales and the prevalence of mass wasting acted as primary controls on the stacking patterns of terrigenous and carbonate lithologies of the Bone Spring Formation, not only on the shelf margin and upper slope, but also in the distal, basinal deposits of the Delaware Basin.
Introduction: Active Margins in Transition—Magmatism and Tectonics through Time: An Issue in Honor of Arthur W. Snoke
Authors: McGrew Allen J. , Schwartz Joshua J.
Published: June 2021

The evolution of active margins through time is the record of plate tectonics as inscribed on the continents. This themed issue honors the eclectic contributions of Arthur W. Snoke (Fig. 1) to the study of active margins with a series of papers that amply demonstrate the broad scope of active margin tectonics and the diverse methods that tectonic geologists employ to decipher their histories. Taken together, this set of papers illustrates the diversity of boundary conditions that guide the development of active margins and the key parameters that regulate their evolution in time and space.
Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS
Authors: Kirichenko E. Yu. , Skatchkov S. N. , Ermakov A. M.
Published: June 2021

Abstract—

Numerous data obtained in the last 20 years indicate that all parts of the mature central nervous system, from the retina and olfactory bulb to the spinal cord and brain, contain cells connected by gap junctions (GJs). The morphological basis of the GJs is a group of joined membrane hemichannels called connexons, the subunit of each connexon is the protein connexin. In the central nervous system, connexins show specificity and certain types of them are expressed either in neurons or in glial cells. Connexins and GJs of neurons, combining certain types of inhibitory hippocampal and neocortical neuronal ensembles, provide synchronization of local impulse and rhythmic activity, thalamocortical conduction, control of excitatory connections, which reflects their important role in the processes of perception, concentration of attention and consolidation of memory, both on the cellular and at the system level. Connexins of glial cells are ubiquitously expressed in the brain, and the GJs formed by them provide molecular signaling and metabolic cooperation and play a certain role in the processes of neuronal migration during brain development, myelination, tissue homeostasis, and apoptosis. At the same time, mutations in the genes of glial connexins, as well as a deficiency of these proteins, are associated with such diseases as congenital neuropathies, hearing loss, skin diseases, and brain tumors. This review summarizes the existing data of numerous molecular, electrophysiological, pharmacological, and morphological studies aimed at progress in the study of the physiological and pathophysiological significance of glial and neuronal connexins and GJs for the central nervous system.
Chemotherapy with paclitaxel for recalcitrant molluscum contagiosum in an HIV-infected patient
Authors: Ugarte Shannon , Mehrmal Sino , Knopf Kevin
Published: June 2021

Molluscum contagiosum (MC) is a viral skin infection seen in children, sexually active adults and immunocompromised populations. It is usually a self-limiting illness that typically spontaneously resolves without therapeutic intervention. However, when the papules are extensive or refractory causing complications or aesthetic issues, multiple treatment modalities exist to relieve symptoms, limit spread and decrease the social stigma associated with visible lesions. Treatment is especially important in HIV/AIDS infected populations, where prevalence is estimated between 5% and 18% and susceptibility to larger, widespread and recalcitrant lesions involving atypical distributions is more common. We evaluated a 38-year-old woman with a history of AIDS (CD4+ T cell count <25 cells/µL) and poor adherence with antiretroviral therapy who presented with a 9-month history of persistent, progressively worsening facial and truncal umbilicated papules consistent with recalcitrant MC refractory to cidofovir injections. She was successfully treated with paclitaxel with complete resolution of the lesions after four cycles without adverse effects.
Big food and the World Health Organization: a qualitative study of industry attempts to influence global-level non-communicable disease policy
Authors: Lauber Kathrin , Rutter Harry , Gilmore Anna B
Published: June 2021

Introduction

There is an urgent need for effective action to address the over 10 million annual deaths attributable to unhealthy diets. Food industry interference with policies aimed at reducing non-communicable diseases (NCDs) is widely documented at the national level but remains under-researched at the global level. Thus, this study explores how ultra-processed food industry actors have attempted to influence NCD policy at WHO.

Methods

A combination of inductive and deductive thematic coding of internal industry documents, academic literature and interviews with key informants from international organisations and global civil society was used to identify action-based strategies ultra-processed food industry actors employ to influence global-level policy.

Results

Ultra-processed food industry actors have attempted to influence WHO and its policies through three main action-based strategies: coalition management, involvement in policy formulation, and information management. Coalition management includes the creation and use of overt alliances between corporations—business associations—and more covert science-focused and policy-focused intermediaries, the hiring of former WHO staff and attempted co-option of civil society organisations. Industry involvement in policy formulation is operationalised largely through the lobbying of Member States to support industry positions, and business associations gaining access to WHO through formal consultations and hearings. Information management involves funding and disseminating research favourable to commercial interests, and challenging unfavourable evidence.

Conclusion

We provide novel insights into how ultra-processed food industry actors shape global-level NCD policy and identify a clear need to guard against commercial interference to advance NCD policy. In their approach, the political behaviour of multinational food corporations bears similarities to that of the tobacco industry. Increased awareness of, and safeguarding against, commercial interference at the national as well as the global level have the potential to strengthen the crucial work of WHO.
Warwick-India-Canada (WIC) global mental health group: rationale, design and protocol
Authors: Singh Swaran P , Mohan Mohapradeep , Iyer Srividya N , Meyer Caroline , Currie Graeme , Shah Jai , Madan Jason , Birchwood Max , Sood Mamta , Ramachandran Padmavati , Chadda Rakesh K , Lilford Richard J , Rangaswamy Thara , Furtado Vivek
Published: June 2021

Introduction

The primary aim of the National Institute of Health Research-funded global health research group, Warwick-India-Canada (WIC), is to reduce the burden of psychotic disorders in India. India has a large pool of undetected and untreated patients with psychosis and a treatment gap exceeding 75%. Evidence-based packages of care have been piloted, but delivery of treatments still remains a challenge. Even when patients access treatment, there is minimal to no continuity of care. The overarching ambition of WIC programme is to improve patient outcomes through (1) developing culturally tailored clinical interventions, (2) early identification and timely treatment of individuals with mental illness and (3) improving access to care by exploiting the potential of digital technologies.

Methods and analysis

This multicentre, multicomponent research programme, comprising five work packages and two cross-cutting themes, is being conducted at two sites in India: Schizophrenia Research Foundation, Chennai (South India) and All India Institute of Medical Sciences, New Delhi (North India). WIC will (1) develop and evaluate evidence-informed interventions for early and first-episode psychosis; (2) determine pathways of care for early psychosis; (3) investigate the efficacy and cost-effectiveness of community care models, including digital and mobile technologies; (4) develop strategies to reduce the burden of mental illnesses among youth; (5) assess the economic burden of psychosis on patients and their carers; and (6) determine the feasibility of an early intervention in psychosis programme in India.

Ethics and dissemination

This study was approved by the University of Warwick’s Biomedical and Scientific Research Ethics Committee (reference: REGO-2018-2208), Coventry, UK and research ethics committees of all participating organisations. Research findings will be disseminated through peer-reviewed scientific publications, presentations at learnt societies and visual media.
What risks to sustainability are identified throughout care bundle implementation and how can they be addressed? A mixed methods case study
Authors: Lennox Laura , Eftychiou Linda , Matthew Dionne , Dowell Jackie , Winn Trish
Published: June 2021

Objectives

Despite national guidance on how to identify and treat heart failure (HF), variation in HF care persists across UK hospitals. Care bundles have been proposed as a mechanism to deliver reliable optimal care for patients; however, specific challenges to sustain care bundles in practice have been highlighted. With few studies providing insight into how to design or implement care bundles to optimise sustainability, there is little direction for practitioners seeking to ensure long-term impact of their initiatives. This study explores the sustainability risks encountered throughout the implementation of a HF care bundle (HFCB) and describes how these challenges were addressed by a multidisciplinary team (MDT) to enhance sustainability over time.

Design

A longitudinal mixed method case study examined the HFCB improvement initiative from September 2015 to August 2018. A standardised sustainability tool was used to collect perceptions of sustainability risks and actions throughout the initiative. Observations, key-informant interviews and documentary analysis were conducted to gain in-depth understanding of how the MDT influenced sustainability through specific actions. A qualitative database was developed using a consolidated sustainability framework to conduct thematic analysis. Sustainability outcomes were explored 1-year post funding to ascertain progress towards sustainment.

Results

The MDT identified six sustainability challenges for the HFCB: infrastructure limitations, coding reliability, delivery consistency, organisational fit, resource stability and demonstrating impact. The MDT undertook multiple actions to enhance sustainability, including: (1) developing a business case to address infrastructure limitations; (2) incorporating staff feedback to increase bundle usability; (3) establishing consistent training; (4) increasing reliability of baseline data; (5) embedding monitoring and communication; and (6) integrating the bundle into current practices.

Conclusion

Through the description of challenges, actions and learning from the MDT, this study provides practical lessons for practitioners and researchers seeking to embed and sustain care bundles in practice.
Long-term impact of a single interprofessional education high-fidelity simulation experience: a pilot study
Authors: Gunaldo Tina , Rosenbaum Cornelius , Davis Alison
Published: June 2021

The interprofessional education (IPE) simulation literature lacks research assessing long-term IPE outcomes. During the 2018-19 and 2019-20 academic year, third year and fourth year medical students, respectively, engaged in an IPE simulation experience focused on cardiopulmonary resuscitation. Students completed the Interprofessional Collaborative Competencies Attainment Survey. There was a statistically significant positive change (p<0.05) in student perceptions of their interprofessional collaborative skills immediately following a single IPE simulation activity for both third and fourth year students. However, a statistically significant decline in means was noted from third year post-questions to fourth year pre-questions. A single annual IPE simulation activity may not be sufficient to support students in building confidence in their collaborative skills without regression.
Phase II clinical trial using anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) consolidation therapy for HER2 negative (0–2+) metastatic breast cancer
Authors: Lum Lawrence G. , Al-Kadhimi Zaid , Deol Abhinav , Kondadasula Vidya , Schalk Dana , Tomashewski Elyse , Steele Patricia , Fields Kristie , Giroux Melissa , Liu Qin , Flaherty Lawrence , Simon Michael , Thakur Archana
Published: June 2021

Background

Metastatic human epidermal growth receptor II (HER2) negative breast cancer remains incurable. Our phase I study showed that anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) may be effective against HER2-tumors. This phase II trial evaluates the efficacy and immune responses of HER2 BATs given to patients with metastatic HER2-estrogen and/or progesterone receptor positive (HR+) and triple negative breast cancer (TNBC) as immune consolidation after chemotherapy. The primary objective of this study was to increase the traditional median time to progression after failure of first-line therapy of 2–4 months with the secondary endpoints of increasing overall survival (OS) and immune responses.

Methods

HER2- metastatic breast cancer (MBC) patients received 3 weekly infusions of HER2 BATs and a boost after 12 weeks.

Results

This phase II study included 24 HER2-HR+ and 8 TNBC patients who received a mean of 3.75 and 2.4 lines of prior chemotherapy, respectively. Eight of 32 evaluable patients were stable at 4 months after the first infusion. There were no dose limiting toxicities. Tumor markers decreased in 13 of 23 (56.5%) patients who had tumor markers. The median OS was 13.1 (95% CI 8.6 to 17.4), 15.2 (95% CI 8.6 to 19.8), and 12.3 (95% CI 2.1 to 17.8) months for the entire group, HER2-HR+, and TNBC patients, respectively. Median OS for patients with chemotherapy-sensitive and chemotherapy-resistant disease after chemotherapy was 14.6 (9.6–21.8) and 8.6 (3.3–17.3) months, respectively. There were statistically significant increases in interferon-γ immunospots, Th1cytokines, Th2cytokines, and chemokines after HER2 BATs infusions.

Conclusions

In heavily pretreated HER2-patients, immune consolidation with HER2 BATs after chemotherapy appears to increase the proportion of patients who were stable at 4 months and the median OS for both groups as well as increased adaptive and innate antitumor responses. Future studies combining HER2 BATs with checkpoint inhibitors or other immunomodulators may improve clinical outcomes.
Mesoporous silica nanoparticles inflame tumors to overcome anti-PD-1 resistance through TLR4-NFκB axis
Authors: Sun Mayu , Gu Pengfei , Yang Yang , Yu Luodan , Jiang Zheshun , Li Jingquan , Le Yingying , Chen Yu , Ba Qian , Wang Hui
Published: June 2021

Background

The clinical benefits of antiprogrammed cell death protein 1 (PD-1) therapy are compromised by resistance in immunologically cold tumors. Convergence of immunotherapy and bioengineering is potential to overcome the resistance. Mesoporous silica nanoparticles (MSNs) are considered the most promising inorganic biological nanomaterials for clinical transformation, however, the fundamental influence of MSNs on immunotherapy is unclear. In this study, we aimed to investigate the role of MSNs in tumor resensitization and explore the feasibility of MSNs combined with anti-PD-1 in cancer therapy.

Methods

Intrinsic and acquired resistant tumors, as well as spontaneous and secondary tumor recurrence models, were used to evaluate the influence of MSNs and the synergistical effect with anti-PD-1 therapy. The roles of CD8+ cytotoxic T-lymphocytes (CTLs) and macrophages were assessed in Rag-1-/- mice, ovalbumin/OT-1 TCR transgenic T-cell system, and other blocking mice models. Mechanistic studies were processed by transcriptomics analysis and conducted in primary cells, in vitro coculture systems, and Toll-like receptor 4 (TLR4) knockout mice.

Results

Both granular and rod-shaped MSNs efficiently overcame tumor resistance with dependence on diameter and aspect ratio. Only once injection of MSNs in prior to anti-PD-1 markedly improved the treatment efficacy, protective immunity, and prognosis. MSNs per se boosted infiltration of CTLs as the early event (days 2–3); and synergistically with anti-PD-1 therapy, MSNs rapidly established a T cell-inflamed microenvironment with abundant high-activated (interferon-γ/tumor necrosis factor-α/Perforin/GranzymeB) and low-exhausted (PD-1/lymphocyte-activation gene 3 (LAG-3)/T-cell immunoglobulin and mucin-domain containing-3 (TIM-3)) CTLs. Chemokines Ccl5/Cxcl9/Cxcl10, which were produced predominantly by macrophages, promoted MSNs-induced CTLs infiltration. MSNs led to high Ccl5/Cxcl9/Cxcl10 production in vitro and in mice through regulating TLR4-NFκB axis. Blocking TLR4-NFκB axis in macrophages or CTLs infiltration abrogated MSNs-induced resensitization to anti-PD-1 therapy.

Conclusions

MSNs efficiently and rapidly inflame immunologically cold tumors and resensitize them to anti-PD-1 therapy through TLR4-NFκB-Ccl5/Cxcl9/Cxcl10 axis. MSNs-based theranostic agents can serve as sensitizers for patients with resistant tumors to improve immunotherapy.
Implications of mRNA-based SARS-CoV-2 vaccination for cancer patients
Authors: Romano Emanuela , Pascolo Steve , Ott Patrick
Published: June 2021

SARS-CoV-2 infection and the resulting COVID-19 have afflicted millions of people in an ongoing worldwide pandemic. Safe and effective vaccination is needed urgently to protect not only the general population but also vulnerable subjects such as patients with cancer. Currently approved mRNA-based SARS-CoV-2 vaccines seem suitable for patients with cancer based on their mode of action, efficacy, and favorable safety profile reported in the general population. Here, we provide an overview of mRNA-based vaccines including their safety and efficacy. Extrapolating from insights gained from a different preventable viral infection, we review existing data on immunity against influenza A and B vaccines in patients with cancer. Finally, we discuss COVID-19 vaccination in light of the challenges specific to patients with cancer, such as factors that may hinder protective SARS-CoV-2 immune responses in the context of compromised immunity and the use of immune-suppressive or immune-modulating drugs.
Swimming capability of target fish from eight hydropower stations in China relative to fishway design
Authors: Shi Xiaotao , Ke Senfan , Tu Zhiying , Wang Yongmeng , Tan Junjun , Guo Wentao
Published: June 2021

The four major Chinese carp (MC), Schizothorax fish species (SF), and Cobitidae fish species (CF) are the most important target fish species in China. The swimming behaviour study of three target fish groups is the key to Chinese fishway designs. The 20 min critical swimming speed (Ucrit-20 min) and endurance of the target fish species in relation to body length, swimming speed, and water temperature were estimated using multiple linear regression. The results indicated that both fish body length and water temperature had a significant effect on swimming capability. Performance comparisons indicated that SF were remarkably strong swimmer. CF possess slightly greater swimming capability than MC. The entrance velocity of the upstream fishway should be greater than Ucrit-20 min, but less than maximum swimming speed to make the flow out of the fishway noticeable. The maximum swimming distance could be estimated using endurance model at flow velocity of 1.2 m·s–1. For the downstream-migrating juvenile fish, it was suggested that the flow velocity of turbine intake should be less than maximum sustained speed avoiding entering turbine.
Electronic wavefunction with maximally entangled MPS representation
Authors: Graswald Benedikt R. , Friesecke Gero
Published: June 2021

We present an example of an electronic wavefunction with maximally entangled MPS representation, in the sense that the bond dimension is maximal and cannot be lowered by any re-ordering of the underlying one-body basis. Our construction works for any number of electrons and orbitals.
The breakthrough of a quantum chemist by classical dynamics: Martin Karplus and the birth of computer simulations of chemical reactions
Authors: Macuglia Daniele , Roux Benoît , Ciccotti Giovanni
Published: June 2021

1964–1965 was an early, crucial period in Martin Karplus’ research—a time when, rather unexpectedly, he approached the problem of reactive collisions using a quasiclassical approximation with the aid of computer technologies. This marked a substantial departure from the quantum-chemical studies of nuclear magnetic resonance that had, until then, dominated his work. The historical perspective outlined by George Schatz, as well Karplus’ own biography, partly frames the contours of this remarkable period in the history of theoretical chemistry. Yet, the available historical literature is not sufficiently complete to allow us to understand Karplus’ transition from nuclear magnetic resonance to reaction dynamics. In this article, we discuss the intellectual ground on which Karplus operated around 1964, further commenting on the relevance of his quantum and quasiclassical studies and pondering how Karplus’ approach eventually led to his interest in the simulation of complex biomolecules.
Coupled network analysis revealing global monthly scale co-variability patterns between sea-surface temperatures and precipitation in dependence on the ENSO state
Authors: Ekhtiari Nikoo , Ciemer Catrin , Kirsch Catrin , Donner Reik V.
Published: June 2021

The Earth’s climate is a complex system characterized by multi-scale nonlinear interrelationships between different subsystems like atmosphere and ocean. Among others, the mutual interdependence between sea surface temperatures (SST) and precipitation (PCP) has important implications for ecosystems and societies in vast parts of the globe but is still far from being completely understood. In this context, the globally most relevant coupled ocean–atmosphere phenomenon is the El Niño–Southern Oscillation (ENSO), which strongly affects large-scale SST variability as well as PCP patterns all around the globe. Although significant achievements have been made to foster our understanding of ENSO’s global teleconnections and climate impacts, there are many processes associated with ocean–atmosphere interactions in the tropics and extratropics, as well as remote effects of SST changes on PCP patterns that have not yet been unveiled or fully understood. In this work, we employ coupled climate network analysis for characterizing dominating global co-variability patterns between SST and PCP at monthly timescales. Our analysis uncovers characteristic seasonal patterns associated with both local and remote statistical linkages and demonstrates their dependence on the type of the current ENSO phase (El Niño, La Niña or neutral phase). Thereby, our results allow identifying local interactions as well as teleconnections between SST variations and global precipitation patterns.
Neohesperidin Induces Cell Cycle Arrest, Apoptosis, and Autophagy via the ROS/JNK Signaling Pathway in Human Osteosarcoma Cells
Authors: Wang Shubin , Li Zongguang , Liu Wei , Wei Guojun , Yu Naichun , Ji Guangrong
Published: June 2021

Neohesperidin has anti-oxidative and anti-inflammatory properties and exerts extensive therapeutic effects on various cancers. In this study, the osteosarcoma cell lines were exposed to different concentrations of neohesperidin. Cell proliferation and viability were assessed by CCK-8 and colony-formation assays. The role of neohesperidin in cell cycle progression and apoptosis were analyzed by flow cytometry and western blotting. To identify autophagosomes and autolysosomes, we used a tandem GFP-mRFP-LC3B lentiviral construct. In addition, autophagy was evaluated by examining autophagosome formation using transmission electron microscopy. Intracellular reactive oxygen species (ROS) production was detected by fluorescence microscopy and flow cytometry. Subsequently, the activation of the ROS/JNK signaling pathway was investigated. Neohesperidin could inhibit proliferation and induce apoptosis in SJSA and HOS cells. The formation of autophagosomes indicated that autophagy occurred in neohesperidin-treated cells and the apoptotic effect of neohesperidin was significantly increased after the use of autophagy inhibitors. Subsequently, we found that neohesperidin-induced apoptosis and autophagy were related to the increase in ROS generation and were significantly inhibited by GSH. Moreover, neohesperidin induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of JNK with SP600125 attenuated neohesperidin-induced apoptosis and autophagy simultaneously. Our data indicated that neohesperidin caused G2/M phase arrest and induced apoptosis and autophagy by activating the ROS/JNK pathway in human osteosarcoma cells, suggesting that neohesperidin is a potential drug candidate for the treatment of osteosarcomas.