bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral health and oral care in patients in a surgical context: A quantitative study comparing patients' and nurses' assessments
Authors: Edfeldt Katarina , Jangland Eva , Larsson Ingwall Linn , Wistedt Sandra‐Marie , Gunnarsson Anna‐Karin , Fröjd Camilla
Published: December 2023

Aims

To investigate fundamental care delivery regarding oral care in a surgical context, and to compare patients' self‐reported oral health with registered nurse assessments.

Design

A descriptive and comparative study, with a consecutive selection.

Methods

A patient oral health rating tool, including questions about performed oral care, was distributed to patients (n = 50), at four surgical wards in Sweden. The response rate was 72%. Oral health status was assessed by a registered nurse using the Revised Oral Assessment Guide (ROAG), and a comparison between patient and registered nurse assessment was performed by calculating Cohen's kappa coefficient and percentage agreement.

Results

Patients (38%) reported severe oral symptoms, mostly dry lips and not an adequate amount of saliva, and 80% were not offered help with oral care. ROAG assessments revealed that 74% had problems with oral health. Almost half of the patients (48%) needed assistance with oral care but only 10% received help. Registered nurses assessed the patient's oral health as worse than the patient's self‐assessment did.

Conclusion

There are deficiencies in fundamental care delivery regarding oral care in a surgical care context. Oral health assessments need to be performed by registered nurses. Routines for systematic oral assessments and for oral care need to be implemented by nurse managers to ensure that patients' fundamental care needs are fulfilled.

Implications for the Profession and Patient Care

Oral health assessments need to be performed regularly by registered nurses since it is insufficient that patients self‐assess their oral health. Nurse managers need to provide and implement routines for nurse assessments and oral care in surgical care contexts.

Impact

There are deficiencies in patients' oral health and oral care, and registered nurses need to perform oral health assessments. Nurse managers need to implement routines for registered nurse assessments and oral care.

Patient Contribution

Patients admitted to a surgical ward were included in the study after being screened for inclusion criteria. After participants signed informed consent, they filled in a questionnaire about oral health and oral care, and a registered nurse performed an oral health assessment.

Reporting Method

This study was carried out according to the STROBE checklist.
Care on the move: the gender care gap and intra‐EU mobility
Authors: MILLER NINA
Published: December 2023

The structure, interpretation, and implementation of the European Union (EU) free movement of persons rules mean that when one's circumstances involve caring responsibilities, the quality of one's rights and protections under EU law diminishes. The consequence of this, in the context of the gender care gap, is that women who are exercising their free movement rights and living in another EU member state are exposed to a disproportionately increased risk of legal and physical precarity, poverty, destitution, and exploitation. They face challenges in attaining and retaining rights and are at risk of falling through gaps that exist between legal rules. Furthermore, the gender care gap is not visible. The connection between the gender care gap and the EU free movement rules has not been made by EU policy makers and civil society; there is currently no strategy among EU civil society organizations to represent the lived experience of EU citizens and lobby the EU institutions for progress on gender equality in this regard.
‘Would any of them have suffered from a guilty conscience if they had won?’: Rudolf Wiethölter and post‐Second World War German law1
Authors: SICILIANO DOMENICO
Published: December 2023

This article reads the theory of law of the Frankfurter jurist Rudolf Wiethölter as an ambitious attempt to realize through law the indispensable radical democratization of post‐Second World War German society. The occasion was provided by the resurgence of critical theory and the subsequent and related emergence and affirmation of the student protest movement of 1968 at the Goethe University Frankfurt. Following the thread of the conflict/dialogue at the university with fellow philosopher Jürgen Habermas, the article brings into focus some stages in the evolution of Wiethölter's critical theory of law and of ‘true jurists’.
Benchmarking the nutrient composition and labelling practices of finger foods and snacks for older infants and young children across seven Southeast Asian countries
Authors: Pries Alissa M. , Bassetti Eleonora , White Jessica M. , Mulder Anzélle , Threapleton Diane , Blankenship Jessica
Published: December 2023

Ensuring consumption of nutrient‐dense, safe and appropriate complementary foods among older infants and young children (IYC) 6–36 months of age is critical for enabling optimal growth and development. The ubiquitous availability of and high demand for commercially packaged snack foods has culminated in a growing trend of snack food products specifically produced and promoted for older IYC. Commercially produced complementary foods (CPCF) that are finger foods/snacks often contain added sugars, excessive sodium content and high total sugar content, making them inappropriate for this young population. This study benchmarked the nutrient composition and labelling practices of CPCF finger foods/snacks available for purchase in seven countries in Southeast Asia. The study adapted a nutrient profiling model from the WHO Regional Office for Europe to determine the proportion of products suitable for promotion for older IYC. Of the total 606 products identified, 8.2% were automatically categorized as not suitable because they were confectionery items. Of the remaining 556 products assessed, over 85% failed to meet all nutrient composition requirements, with the presence of added sugars/sweeteners and excessive sodium and total sugar contents the primary reasons for failure. Products also demonstrated concerning labelling practices, with all of the products (98.6%) displaying an inappropriate claim on the label. These findings reveal major concerns with the nutrient composition and labelling practices of CPCF finger foods/snacks in the SEA region and should serve as an alarm bell for regulatory action. National binding legal measures, such as mandatory standards for composition and labelling are urgently needed.
Estimating gravity coefficients with multiple layers of heterogeneity
Authors: Kitenge Erick , Lahiri Sajal
Published: December 2023

We estimate a gravity model for 205 countries, with data from 1954 to 2014, allowing for multiple layers of heterogeneity. The first layer arises from the interactions between a set of traditional gravity variables. The second one comes from country pairs that differ in values of the binary time‐independent gravity variables. Further layers come from different income groups and regions. Our results show the importance of heterogeneities at various levels. For instance, landlockedness is less restrictive when trading partners are contiguous or colonially linked. We also find, for example, that the positive interaction between landlockedness and contiguity is more (less) pronounced when non‐high‐income countries import (export) or when Middle East and North Africa (MENA) countries import, and the negative interaction between landlockedness and language similarities is stronger when MENA countries export.
Spillovers from government policy during a crisis: Evidence from international trade during COVID‐19 lockdowns
Authors: Cardoso Miguel , Malloy Brandon
Published: December 2023

We examine how variation in the severity of government intervention in response to the COVID‐19 pandemic impacted trade, using a novel dataset on monthly bilateral trade flows between Canadian provinces and U.S. states. Our results show that differences in the collections of policy responses employed by states and provinces throughout the course of the pandemic have had a significant and heterogeneous impact in accounting for variation in changes in aggregate province‐state trade flows. Government interventions around workplace closures and gathering restrictions are associated with the largest drop in bilateral trade flows, especially when introduced by U.S. states and during periods when COVID‐19 case rates are rising, while many pandemic restrictions have no statistically significant impact on trade flows.
Factors associated with mortality in HIV‐TB co‐infected patients during and after the course of TB treatment in high‐burden settings, Mumbai, India: A cohort analysis
Authors: Acharya Shrikala , Karanjkar Vijaykumar , Bhamre Sunil P. , Palkar Amol , Rathod Dhirubhai , Setia Maninder Singh
Published: December 2023

Background

Knowledge of factors associated with TB mortality during treatment and post treatment will help us develop better monitoring and implementation strategies for TB control. We designed the present study to examine the factors associated with mortality in HIV‐TB co‐infected patients during and after the course of TB treatment.

Methods

This study is a cohort analysis of secondary data collected from 1804 HIV‐TB co‐infected individuals from 16 anti‐retroviral therapy (ART) centres affiliated with the Mumbai Districts AIDS Control Society, Mumbai, India. We used Kaplan Meier survival curves and hazard ratios to estimate the mortality in patients.

Results

The overall mortality rate in this cohort was 1.14 per 100 per month. The mortality proportion was 18% (95% CI: 16.1%, 20.1%) during treatment and 10.6% (95% CI: 8.9%, 12.5%) in the post‐treatment period. Mortality was significantly higher in those with a CD4 count 0–200 cells/mm3 (HR: 3.04, 95% CI: 2.13, 4.15; p < 0.001), and in patients who were ART naïve and referred to the ART centre with a diagnosis of TB (HR: 1.39, 95% CI: 1.06, 1.82; p = 0.016). Mortality was also significantly higher in the first 6 months after initiation of ART (HR: 1.36, 95% CI: 1.06, 1.75; p = 0.016). A decrease in the CD4 counts from initial levels at start of TB treatment to end of TB treatment was associated with higher mortality in the post‐treatment period.

Discussion

The overall mortality remains high; early identification of TB and HIV disease, and use of rapid point of care tests for diagnosis of TB are needed across all health care facilities. Post‐treatment follow‐up and monitoring is important in HIV‐TB co‐infected patients, and post‐treatment mortality should also be considered as one of the indicators for successful TB control programmes.
Tangential Shear Considerations
Authors:   Commentary Task Group
Published: December 2023

This paper presents the historical development of tangential shear considerations for concrete containments in the United States.

About forty years ago, the first major generation of concrete containments were under design in the United States. In general, the reinforced containments used both an orthogonal (hoop, vertical) and inclined (diagonal) reinforcing system. The orthogonal reinforcing was designed to resist membrane loads and the inclined system resisted the tangential shear. Prestressed containments allowed a concrete principal tension stress for various loading combinations which included earthquake loads.
Blast Tests on Pre-Stressed Concrete Slabs
Authors:   Commentary Task Group
Published: December 2023

The behaviour of reinforced concrete under blast loading is well understood. However, the behaviour of pre-stressed concrete under higher levels of pre-stressing, subjected to blast loading, has not been studied extensively. A blast testing program on pre-stressed, concrete slabs was established to define design acceptance criteria for pre-stressed concrete elements for nuclear structures. The American Society of Mechanical Engineers (ASME) testing program is a part of a code provision update put in place under the Joint Task Group ASME BPVC Section III Division 2 (Nuclear Concrete Containment) and ACI 349 (Nuclear Safety Related Structures). The paper presents six tests on pre-stressed concrete slabs with the same geometry (4.88m x 4.88m x 0.27 m) but with three different designs of the reinforcement and pre- stressing. The reinforcement ratio as well as the pre-stressing levels was chosen to reflect the design of existing nuclear containment buildings as well as the design of new builds currently under construction, or to be constructed in the near future. The pre-stressing for all slabs was introduced using post tensioning with grouted tendons. Two different levels of pre-stressing were introduced in the slabs: 5 MPa and 10 MPa, typical for nuclear containments. The slabs were reinforced with two different amounts of reinforcement: 95 kg/m3 and 220 kg/m3. The amount of distant ANFO explosive charge was defined to obtain different target levels of support rotations for each slab design. The main response mode observed in the tests was a flexural mode with brittle failure of the concrete under compression.
Genomic analyses reveal poaching hotspots and illegal trade in pangolins from Africa to Asia
Authors: Tinsman Jen C. , Gruppi Cristian , Bossu Christen M. , Prigge Tracey-Leigh , Harrigan Ryan J. , Zaunbrecher Virginia , Koepfli Klaus-Peter , LeBreton Matthew , Njabo Kevin , Wenda Cheng , Xing Shuang , Abernethy Katharine , Ades Gary , Akeredolu Excellence , Andrew Imuzei B. , Barrett Taneisha A. , Bernáthová Iva , Černá Bolfíková Barbora , Diffo Joseph L. , Difouo Fopa Ghislain , Ebong Lionel Esong , Godwill Ichu , Koumba Pambo Aurélie Flore , Labuschagne Kim , Nwobegahay Mbekem Julius , Momboua Brice R. , Mousset Moumbolou Carla L. , Ntie Stephan , Rose-Jeffreys Elizabeth , Simo Franklin T. , Sundar Keerthana , Swiacká Markéta , Takuo Jean Michel , Talla Valery N. K. , Tamoufe Ubald , Dingle Caroline , Ruegg Kristen , Bonebrake Timothy C. , Smith Thomas B.
Published: December 2023

The white-bellied pangolin (
Phataginus tricuspis
) is the world’s most trafficked mammal and is at risk of extinction. Reducing the illegal wildlife trade requires an understanding of its origins. Using a genomic approach for tracing confiscations and analyzing 111 samples collected from known geographic localities in Africa and 643 seized scales from Asia between 2012 and 2018, we found that poaching pressures shifted over time from West to Central Africa. Recently, Cameroon’s southern border has emerged as a site of intense poaching. Using data from seizures representing nearly 1 million African pangolins, we identified Nigeria as one important hub for trafficking, where scales are amassed and transshipped to markets in Asia. This origin-to-destination approach offers new opportunities to disrupt the illegal wildlife trade and to guide anti-trafficking measures.
What does it mean to trust a technology?
Authors: Stilgoe Jack
Published: December 2023

A
survey published in October 2023
revealed what seemed to be a paradox. Over the past decade, self-driving vehicles have improved immeasurably, but public trust in the technology is low and falling. Only 37% of Americans said they would be comfortable riding in a self- driving vehicle, down from 39% in 2022 and 41% in 2021. Those that have used the technology express more enthusiasm, but the rest have seemingly had their confidence shaken by the failure of the technology to live up to its hype.
Flagellar interference with plasmid uptake in biofilms: a joint experimental and modeling study
Authors: Røder Henriette Lyng , Christidi Eleni , Amador Cristina I. , Music Samra , Olesen Asmus Kalckar , Svensson Birte , Madsen Jonas Stenløkke , Herschend Jakob , Kreft Jan-Ulrich , Burmølle Mette
Published: December 2023

Plasmid conjugation is a key facilitator of horizontal gene transfer (HGT), and plasmids encoding antibiotic resistance drive the increasing prevalence of antibiotic resistance. In natural, engineered, and clinical environments, bacteria often grow in protective biofilms. Therefore, a better understanding of plasmid transfer in biofilms is needed. Our aim was to investigate plasmid transfer in a biofilm-adapted wrinkly colony mutant of
Xanthomonas retroflexus
(XRw) with enhanced matrix production and reduced motility. We found that XRw biofilms had an increased uptake of the broad host-range IncP-1ϵ plasmid pKJK5 compared to the wild type (WT). Proteomics revealed fewer flagellar-associated proteins in XRw, suggesting that flagella were responsible for reducing plasmid uptake. This was confirmed by the higher plasmid uptake of non-flagellated
fliM
mutants of the
X. retroflexus
wrinkly mutant as well as the wild type. Moreover, testing several flagellar mutants of
Pseudomonas putida
suggested that the flagellar effect was more general. We identified seven mechanisms with the potential to explain the flagellar effect and simulated them in an individual-based model. Two mechanisms could thus be eliminated (increased distances between cells and increased lag times due to flagella). Another mechanism identified as viable in the modeling was eliminated by further experiments. The possibility of steric hindrance of pilus movement and binding by flagella, reducing the frequency of contact and thus plasmid uptake, proved viable, and the three other viable mechanisms had a reduced probability of plasmid transfer in common. Our findings highlight the important yet complex effects of flagella during bacterial conjugation in biofilms.

IMPORTANCE

Biofilms are the dominant form of microbial life and bacteria living in biofilms are markedly different from their planktonic counterparts, yet the impact of the biofilm lifestyle on horizontal gene transfer (HGT) is still poorly understood. Horizontal gene transfer by conjugative plasmids is a major driver in bacterial evolution and adaptation, as exemplified by the troubling spread of antibiotic resistance. To either limit or promote plasmid prevalence and dissemination, we need a better understanding of plasmid transfer between bacterial cells, especially in biofilms. Here, we identified a new factor impacting the transfer of plasmids, flagella, which are required for many types of bacterial motility. We show that their absence or altered activity can lead to enhanced plasmid uptake in two bacterial species,
Xanthomonas retroflexus
and
Pseudomonas putida
. Moreover, we demonstrate the utility of mathematical modeling to eliminate hypothetical mechanisms.
Wastewater-based surveillance as a tool for public health action: SARS-CoV-2 and beyond
Authors: Parkins Michael D. , Lee Bonita E. , Acosta Nicole , Bautista Maria , Hubert Casey R. J. , Hrudey Steve E. , Frankowski Kevin , Pang Xiao-Li
Published: December 2023

Wastewater-based surveillance (WBS) has undergone dramatic advancement in the context of the coronavirus disease 2019 (COVID-19) pandemic. The power and potential of this platform technology were rapidly realized when it became evident that not only did WBS-measured SARS-CoV-2 RNA correlate strongly with COVID-19 clinical disease within monitored populations but also, in fact, it functioned as a leading indicator. Teams from across the globe rapidly innovated novel approaches by which wastewater could be collected from diverse sewersheds ranging from wastewater treatment plants (enabling community-level surveillance) to more granular locations including individual neighborhoods and high-risk buildings such as long-term care facilities (LTCF). Efficient processes enabled SARS-CoV-2 RNA extraction and concentration from the highly dilute wastewater matrix. Molecular and genomic tools to identify, quantify, and characterize SARS-CoV-2 and its various variants were adapted from clinical programs and applied to these mixed environmental systems. Novel data-sharing tools allowed this information to be mobilized and made immediately available to public health and government decision-makers and even the public, enabling evidence-informed decision-making based on local disease dynamics. WBS has since been recognized as a tool of transformative potential, providing near-real-time cost-effective, objective, comprehensive, and inclusive data on the changing prevalence of measured analytes across space and time in populations. However, as a consequence of rapid innovation from hundreds of teams simultaneously, tremendous heterogeneity currently exists in the SARS-CoV-2 WBS literature. This manuscript provides a state-of-the-art review of WBS as established with SARS-CoV-2 and details the current work underway expanding its scope to other infectious disease targets.
KSHV-encoded LANA bypasses transcriptional block through the stabilization of RNA Pol II in hypoxia
Authors: Bose Dipayan , Singh Rajnish Kumar , Robertson Erle S.
Published: December 2023

Hypoxia results from an insufficient supply of oxygen, which results in physiological stress in biological systems. Cells respond to this unfavorable condition by reducing critical cellular functions, which include replication, transcription, and translation. Oncogenic Kaposi sarcoma-associated virus (KSHV) undergoes lytic reactivation in hypoxic conditions. Furthermore, reactivation requires the synthesis of specific viral proteins, both structural and non-structural. Therefore, the virus manipulates the cellular microenvironment to ensure efficient functioning of the cellular transcription machinery, including RNA polymerase II (Pol II), by protecting it from hypoxia-mediated degradation. In this study, we demonstrated that hypoxia induces degradation of RNA Pol II via ubiquitination mediated by the NEDD4 E3 ligase, which results in transcription inhibition. However, in KSHV-infected cells during hypoxia, the virus-encoded latency-associated nuclear antigen interacts with NEDD4, inhibiting its E3 ubiquitin ligase activity and requires complex formation with hypoxia inducible factor HIF1α. This activity inhibits the polyubiquitination of RNA Pol II to maintain steady transcription levels necessary for the synthesis of the essential viral genes needed for successful lytic reactivation.

IMPORTANCE

Hypoxia can induce the reactivation of Kaposi sarcoma-associated virus (KSHV), which necessitates the synthesis of critical structural proteins. Despite the unfavorable energetic conditions of hypoxia, KSHV utilizes mechanisms to prevent the degradation of essential cellular machinery required for successful reactivation. Our study provides new insights on strategies employed by KSHV-infected cells to maintain steady-state transcription by overcoming hypoxia-mediated metabolic stress to enable successful reactivation. Our discovery that the interaction of latency-associated nuclear antigen with HIF1α and NEDD4 inhibits its polyubiquitination activity, which blocks the degradation of RNA Pol II during hypoxia, is a significant contribution to our understanding of KSHV biology. This newfound knowledge provides new leads in the development of novel therapies for KSHV-associated diseases.
Microbiota-accessible fiber activates short-chain fatty acid and bile acid metabolism to improve intestinal mucus barrier in broiler chickens
Authors: Yang Jiantao , Qin Kailong , Sun Yanpeng , Yang Xiaojun
Published: December 2023

Dietary polysaccharides are closely associated with gut microbiota and intestinal function homeostasis. This study aimed to investigate the mechanisms by which the β-glucan, arabinoxylan, and resistant starch selectively modulate gut microbiota and microbiota-derived metabolites to protect the intestinal mucus barrier in broiler chicken. In the present study, cecal microbiota samples from 21-day-old broilers were cultured
in vitro
with β-glucan, arabinoxylan, or resistant starch as the sole carbon source. We found that β-glucan, arabinoxylan and resistant starch alter community structure and selectively target the enrichment of
Bacteroides
,
Lactobacillus, Coprococcus
,
Butyricicoccus
,
Ruminococcus
and
Blautia
, respectively. Notably, supplementing fiber-deficient diets with arabinoxylan and resistant starch, but not with β-glucan, improved the intestinal mucus barrier by cecal microbiota enrichment and increase in the concentration of microbiota-derived short-chain fatty acids (SCFAs). In addition, we illustrated through bacterial cultures
in vitro
that the supplementation of arabinoxylan and resistant starch resulted in a change in bacterial biotransformation of secondary bile acids. Our findings provide insight into how arabinoxylan and resistant starch may selectively target gut microbiota and mediate the production of SCFAs and bile acid biotransformation to improve intestinal mucus barrier function.

IMPORTANCE

The intestinal mucus barrier, located at the interface of the intestinal epithelium and the microbiota, is the first line of defense against pathogenic microorganisms and environmental antigens. Dietary polysaccharides, which act as microbiota-accessible fiber, play a key role in the regulation of intestinal microbial communities. However, the mechanism via which dietary fiber affects the intestinal mucus barrier through targeted regulation of the gut microbiota is not clear. This study provides fundamental evidence for the benefits of dietary fiber supplementation in broiler chickens through improvement in the intestinal mucus barrier by targeted regulation of the gut ecosystem. Our findings suggest that the microbiota-accessible fiber-gut microbiota-short-chain fatty acid/bile acid axis plays a key role in regulating intestinal function.
Hierarchic regulation of a metabolic pathway: H-NS, CRP, and SsrB control
myo
-inositol utilization by
Salmonella enterica
Authors: Felsl Angela , Brokatzky Dominik , Kröger Carsten , Heermann Ralf , Fuchs Thilo M.
Published: December 2023

The metabolic island GEI4417/4436 of
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) enables the degradation of
myo
-inositol (MI) as the sole carbon and energy source. The island encodes two regulatory factors, the autoregulated repressor IolR that inhibits the transcription of most
iol
genes in the absence of MI, and the activator ReiD that induces the expression of an
iol
gene operon that is not controlled by IolR. In this study, we investigated the putative role of global regulators in the control of MI utilization by
S
. Typhimurium. The histone-like nucleoid structuring protein H-NS is demonstrated here to interact with 16 regions of GEI4417/4436 and to silence the transcriptional activity of the promoters P

reiD

and P

iolE

, thus controlling the expression of genes initial for MI degradation. The cAMP-binding regulatory protein (CRP) is shown to bind numerous promoters in GEI4417/4436 and is required for the growth of
S
. Typhimurium strain 14028 in a minimal medium with MI. The binding kinetics of H-NS and CRP toward promoters of GEI4417/4436 were quantified by surface resonance spectroscopy, showing that H-NS weakly binds to promoters of initial genes and that CRP has a high affinity to promoters of all genes essential for MI utilization. Furthermore, three promoters of the metabolic island were identified here to belong to the virulon of the two-component system SsrA/SsrB of salmonellae as demonstrated by electrophoretic mobility shift assays and the use of chromosomal luciferase reporter fusions.

IMPORTANCE

The capacity to utilize myo-inositol (MI) as sole carbon and energy source is widespread among bacteria, among them the intestinal pathogen
S
. Typhimurium. This study elucidates the complex and hierarchical regulation that underlies the utilization of MI by
S
. Typhimurium under substrate limitation. A total of seven regulatory factors have been identified so far, allowing the pathogen an environment-dependent, efficient, and fine-tuned regulation of a metabolic property that provides growth advantages in different environments.
Analysis of antiviral drug properties of thymidine kinase of herpes B virus using recombinant herpes simplex virus 1
Authors: Nguyen Phu Hoang Anh , Fukushi Shuetsu , Yamada Souichi , Harada Shizuko , Yoshikawa Tomoki , Kinoshita Hitomi , Kawahara Madoka , Ogawa Takuma , Ebihara Hideki , Moi Meng Ling , Saijo Masayuki
Published: December 2023

Zoonotic infection by herpes B virus (BV) causes severe neurological disease, which in the absence of appropriate treatment can have a mortality rate of 80%. Long-term administration of acyclovir or ganciclovir is the recommended prophylactic treatment option for BV infections. However, the emergence of acyclovir- and/or ganciclovir-resistant BV may become a major problem. Here, we examined the ability of BV thymidine kinase (TK) from monkeys (mBVTK) and humans (hBVTK) to acquire resistance to acyclovir and ganciclovir. The sequences of mBVTK and hBVTK differ by two amino acids. We constructed and expressed four HSV-1-based recombinant viruses (HSV-1_mBVTK, HSV-1_hBVTK, HSV-1_VZVTK, and HSV_HSV-1TK) in which the HSV-1TK gene was deleted and the TK gene of monkey BV, human BV, varicella-zoster virus, and HSV-1 was inserted, respectively. We then tested the sensitivity of these recombinant viruses to acyclovir, ganciclovir, penciclovir, and brivudine. HSV-1_HSV-1TK and wild-type HSV-1 were more susceptible to ganciclovir, acyclovir, and penciclovir than HSV-1_VZVTK, HSV-1_hBVTK, and HSV-1_mBVTK. Both HSV-1_hBVTK and HSV-1_mBVTK exhibited similar sensitivity profiles against all tested drugs: both were susceptible to acyclovir, ganciclovir, and penciclovir but resistant to brivudine. In addition, we forced HSV-1_hBVTK to replicate under selective pressure from acyclovir or ganciclovir and then examined the ability of the BV TK gene to develop drug resistance. Investigation of the drug-resistant HSV-1_hBVTK gene revealed the absence of amino acid substitutions in BV TK, suggesting that the development of acyclovir- or ganciclovir-resistant BV through mutations in the TK gene is a rare occurrence in this experimental system.

IMPORTANCE

Zoonotic infection of humans with herpes B virus (BV) causes severe neurological diseases. Acyclovir (ACV) and ganciclovir (GCV), most frequently used as anti-herpes drugs, are recommended for prophylaxis and therapy in human BV infection. In this study, we examined the property of BV thymidine kinase (TK) against anti-herpes drugs using a recombinant herpes simplex virus type 1 (HSV-1) carrying BV TK gene. We found that HSV-1 carrying BV TK was similarly sensitive to GCV as HSV-1 carrying varicella zoster virus TK. In addition, we demonstrated that BV TK was not mutated in the GCV- and ACV-resistant HSV-1 carrying BV TK, suggesting that ACV- or GCV-resistant BV might be rare during treatment with these antiviral drugs. These data can provide a new insight into the properties of BV TK in terms of the development of drug resistance.
Clinical impact of metagenomic next-generation sequencing of peripheral blood for the diagnosis of invasive mucormycosis: a single-center retrospective study
Authors: Wang Wei , Yao Yake , Li Xi , Zhang Shanshan , Zeng Zhu , Zhou Hua , Yang Qing
Published: December 2023

This study aims to assess the usefulness of peripheral blood metagenomic next-generation sequencing (mNGS) in diagnosing invasive mucormycosis (IM). We conducted a retrospective analysis of clinical data from 73 patients with mucorales sequences detected by peripheral blood mNGS at the First Affiliated Hospital, Zhejiang University School of Medicine, between February 2021 and December 2022. We examined data on risk factors, clinical symptoms, imaging characteristics, pathogenic findings, clinical diagnoses, and treatment outcomes. Among the 73 patients with mucorales sequences detected by peripheral blood mNGS, 7 cases were confirmed, 12 were probable, 34 were possible, and 20 were false positives, based on the diagnostic criteria for IM. Among the 34 possible cases, patients exhibited risk factors, clinical symptoms, imaging features, and prognoses consistent with IM. In 7 out of the 12 probable cases, the same mucorale nucleic acid was found in peripheral blood mNGS samples collected at an average interval of 8.1 days. In the remaining 20 patients, mucorales nucleic acid was detected in peripheral blood mNGS, but they lacked risk factors or clinical features of mucorales infection and lacked other pathological evidence, leading to a judgment of false positive. The positive predictive value of peripheral blood mNGS for diagnosing invasive mucormycosis in the cases studied was 72.6%. Peripheral blood mNGS testing provides valuable insights for diagnosing invasive mucormycosis. However, it should be used in conjunction with risk factors, clinical features, and other pathogenic test results to make a comprehensive assessment.

IMPORTANCE

Given the high fatality rates, prompt and accurate identification of the fungal culprit is crucial, emphasizing the need for invasive mucormycosis. Unfortunately, mucormycosis lacks definitive biomarkers, depending primarily on smears, cultures, or pathology, all necessitating invasive specimen collection from the infection site. However, obtaining valid specimens early in critically ill patients poses substantial risks and challenges. Whether peripheral blood metagenomic next-generation sequencing (mNGS) can enhance early mucormycosis diagnosis, especially when direct specimen collection from the infection site is challenging, is warranted. This is a large-scale clinical study conducted to evaluate the utility and clinical impact of mNGS of peripheral blood for the diagnosis of invasive mucormycosis. We believe our study provided both novelty in translational medicine and a great value for the medical community to understand the strengths and limitations of mNGS of peripheral blood as a new diagnostic tool for the diagnosis and management of invasive mucormycosis.
Spermine enhances the activity of anti-tuberculosis drugs
Authors: Sao Emani Carine , Reiling Norbert
Published: December 2023

The discovery of molecules that could shorten the treatment period of tuberculosis (TB) holds the promise of improving the current regimen. Polyamines are organic polycationic alkylamines found in millimolar concentrations in all living cells. Spermine (Spm) is a polyamine that was shown (more than 70 years ago) to be toxic to
Mycobacterium tuberculosis
(M.tb). In this study, we used various biochemical assays to assess the mechanism of action of Spm. Furthermore, using various drug susceptibility testing methods, we investigated the ability of Spm to enhance the activity of first-line TB drugs, isoniazid (INH) and rifampicin (RIF), as well as second-line TB drugs, para-aminosalicylic acid (PAS) and bedaquiline (BDQ). Our findings revealed that at toxic concentrations, Spm induced the formation of reactive oxygen species (ROS), a reaction that was influenced by the pH and the iron concentration of the media. Furthermore, the generation of ROS by Spm was associated with increased ferric iron and NADP levels. Moreover, the ROS produced by Spm synergized with the ROS generated by the lipophilic peroxide cumene hydroperoxide (CuOOH), as well as with the ROS generated by RIF and PAS, while enhancing their antimycobacterial activity. Additionally, we found that Spm enhanced the combined activity of INH and RIF against M.tb. Lastly, Spm was also able to enhance the activity of BDQ due to another mechanism of action. This study provides data and findings that would fuel future studies on the suitability of Spm as a potential adjunct TB therapy. The enhanced antimycobacterial activity of TB drugs in combination with Spm could offer promising new avenues for improving TB treatment outcomes.

IMPORTANCE

This is the first study that attempted to demonstrate the mechanisms of reactive oxygen species (ROS) generation by spermine (Spm) in
Mycobacterium tuberculosis
(M.tb). Furthermore, this is the first study to demonstrate that it is able to enhance the activity of currently available and World Health Organization (WHO)-approved tuberculosis (TB) drugs. Spermine can easily be obtained since it is already found in our diet. Moreover, as opposed to conventional antibiotics, it is less toxic to humans since it is found in millimolar concentrations in the body. Finally, with the difficulty of curing TB with conventional antibiotics, this study suggests that less toxic molecules, such as Spm, could in a long-term perspective be incorporated in a TB regimen to boost the treatment.
Effects of variation in sample storage conditions and swab order on 16S vaginal microbiome analyses
Authors: Kumar Tanya , Bryant MacKenzie , Cantrell Kalen , Song Se Jin , McDonald Daniel , Tubb Helena M. , Farmer Sawyer , Lewis Amanda , Lukacz Emily S. , Brubaker Linda , Knight Rob
Published: December 2023

Technical bias is a pressing issue in microbiome research, and variability can be introduced at any stage from sample collection to figure generation. In this study, we aim to reduce biases in studying the human vaginal microbiome by examining the impact of sample storage buffer and multiple swabbing events using 16S rRNA gene amplicon sequencing data generated from vaginal swabs. We show that AssayAssure Genelock, a clinically relevant preservative for urine samples, is effective in preserving vaginal samples for microbiome studies. When comparing Genelock to 95% (vol/vol) ethanol and no preservative (air only), host variability explained more variance in both weighted and unweighted UniFrac measurements than the preservation method. We further examined the impact of three successive self-swabbing events, as the relatively low biomass nature of vaginal samples can inherently introduce bias. It is important to know if taking multiple swabs can provide replicable results and thus allow for additional technical replicates and an increased sample size. We found that up to three swabbing events do not introduce bias when examining the presence or absence of taxa but can explain 3% of the variability in the amount of taxa calculated. A study with more participants is warranted to provide further validation of these findings, but in producing this pilot study, we aim to continue laying the groundwork so that universally standardized and accessible studies can be created.

IMPORTANCE

The composition of the human vaginal microbiome has been linked to a variety of medical conditions including yeast infection, bacterial vaginosis, and sexually transmitted infection. The vaginal microbiome is becoming increasingly acknowledged as a key factor in personal health, and it is essential to establish methods to collect and process accurate samples with self-collection techniques to allow large, population-based studies. In this study, we investigate if using AssayAssure Genelock, a nucleic acid preservative, introduces microbial biases in self-collected vaginal samples. To our knowledge, we also contribute some of the first evidence regarding the impacts of multiple swabs taken at one time point. Vaginal samples have relatively low biomass, so the ability to collect multiple swabs from a unique participant at a single time would greatly improve the replicability and data available for future studies. This will hopefully lay the groundwork to gain a more complete and accurate understanding of the vaginal microbiome.
Structural evolution of the North Himalaya domes as revealed by crustal-scale seismic-reflection surveying
Authors: Shi Zhuoxuan , Gao Rui , Lu Zhanwu , Li Wenhui , Li Hongqiang , Liang Hongda , Qi Rui , Deng Xiaofan , Dong Xinyu
Published: December 2023

As the typical products of collisional orogeny, gneiss domes are important geological units with which to decipher the crustal deformation and evolutionary history of continental collision. However, their formation mechanisms remain poorly understood. This issue is well illustrated by the debate surrounding the origin of the North Himalaya gneiss dome zone, which has been attributed to middle-crustal channel flow, thrust-duplex development, extensional detachment faulting, or diapiric flow related to partial crustal melting. These models predict different internal structures within individual domes that can be tested by high-resolution seismic imaging. Here, we present newly acquired seismic-reflection data collected along an ~120-km-long north-south traverse across the central segment of the North Himalaya gneiss dome zone. Analysis and interpretation of the seismic data constrained by surface geology observations imply that (1) the subducting Indian lower crust is decoupled from the deformed middle and upper crust in the North Himalaya, (2) a crustal-scale stack of antiformal duplexes with a structural thickness of ~35 km defines the cores of the gneiss domes imaged by the seismic survey, and (3) highly reflective, sheetlike bodies imaged in our seismic profile are best interpreted as leucocratic intrusions developed synchronously during gneiss dome development. As a whole, our work suggests that the North Himalaya gneiss dome zone was created by coeval crustal shortening and partial melting of orogenic crust.
Supplemental Material: A global database of Mars-relevant hydrovolcanic environments on Earth with potential biosignature preservation
Authors: Ryan Catheryn H. , al. et
Published: December 2023

 Includes an expanded database with age, composition, setting, location, and structure name(s) for 45 volcanic fields; GIS data compatible with Esri ArcGIS Pro and Google Earth data of all 716 volcanic structures in database; map attribute table with location data for all 716 structures; and compiled major element geochemistry and FeOtotal versus SiO2 and total-alkali silica charts for all volcanic fields where data is available.  
Assessing the influence of abdominal compression on time to return of circulation during resuscitation of asphyxiated newborn lambs: a randomised preclinical study
Authors: Polglase Graeme R , Hwang Colin , Blank Douglas A , Badurdeen Shiraz , Crossley Kelly J , Kluckow Martin , Gill Andrew W , Camm Emily , Galinsky Robert , Brian Yoveena , Hooper Stuart B , Roberts Calum T
Published: December 2023

Objective

During neonatal resuscitation, the return of spontaneous circulation (ROSC) can be achieved using epinephrine which optimises coronary perfusion by increasing diastolic pressure. Abdominal compression (AC) applied during resuscitation could potentially increase diastolic pressure and therefore help achieve ROSC. We assessed the use of AC during resuscitation of asystolic newborn lambs, with and without epinephrine.

Methods

Near-term fetal lambs were instrumented for physiological monitoring and after delivery, asphyxiated until asystole. Resuscitation was commenced with ventilation followed by chest compressions. Lambs were randomly allocated to: intravenous epinephrine (20 µg/kg, n=9), intravenous epinephrine+continuous AC (n=8), intravenous saline placebo (5 mL/kg, n=6) and intravenous saline+AC (n=9). After three allocated treatment doses, rescue intravenous epinephrine was administered if ROSC had not occurred. Time to achieve ROSC was the primary outcome. Lambs achieving ROSC were ventilated and monitored for 60 min before euthanasia. Brain histology was assessed for micro-haemorrhage.

Results

Use of AC did not influence mean time to achieve ROSC (epinephrine lambs 177 s vs epinephrine+AC lambs 179 s, saline lambs 602 s vs saline+AC lambs 585 s) or rate of ROSC (nine of nine lambs, eight of eight lambs, one of six lambs and two of eight lambs, respectively). Application of AC was associated with higher diastolic blood pressure (mean value >10 mm Hg), mean and systolic blood pressure and carotid blood flow during resuscitation. Cortex and deep grey matter micro-haemorrhage was more frequent in AC lambs.

Conclusion

Use of AC during resuscitation increased diastolic blood pressure, but did not impact time to ROSC.
Cryptogenic pyogenic liver abscess caused byFusobacterium necrophorumin an immunocompetent patient
Authors: Salehi Omar , Chen Andrew , Cevik Jevan
Published: December 2023

Pyogenic liver abscesses are potentially fatal conditions that require prompt treatment with drainage and appropriate antimicrobial therapy.Fusobacterium necrophorumis a gram-negative rod that is found in the oral cavity, gastrointestinal tract and female genital tract. It is an extremely rare cause of liver abscess, particularly in the absence of risk factors or exposures. We describe an unusual case of a cryptogenicF. necrophorumhepatic abscess without a clear source despite extensive investigation in a young, immunocompetent patient without known risk factors or exposures for such an infection.
Diagnostic and prognostic role of synovial tissue analysis in juvenile idiopathic arthritis: a monocentric study
Authors: Costi Stefania , Armiraglio Elisabetta , Pregnolato Francesca , Chighizola Cecilia Beatrice , Marino Achille , Randelli Pietro Simone , Parafioriti Antonina , Caporali Roberto
Published: December 2023

Objectives

This study investigates the diagnostic role of synovial tissue analysis in children presenting with arthritis and assesses its prognostic significance to predict clinical outcome in juvenile idiopathic arthritis (JIA).

Methods

Synovial samples of paediatric patients undergoing synovial biopsy between 1995 and 2020 were analysed histologically and immunohistochemically. Relationships between histological/immunohistochemical parameters and clinical variables were assessed.

Results

Synovial biopsy was performed for diagnosis in 65 cases allowing to correctly classify 79% of patients.

At histological analysis on 42 JIA samples, any difference in the number of synovial lining layers, subsynovial elementary lesions, fibrin deposit, Krenn Synovitis Score, inflammatory infiltrate score and pattern emerged between JIA subsets or on treatment exposure. Synovial tissue analysis predicted outcome: higher number of synovial layers predicted worse disease course (>4 flares during follow-up; 4.5 vs 3.0, p=0.035), even after adjusting for age at diagnosis and observation time (OR 2.2, p=0.007); subjects who had switched>2 biological disease-modifying antirheumatic drugs had higher prevalence of subsynovial elementary lesions (55.6% vs 10.3%, p=0.005) and fibrin deposits in synovial lining (60.0% vs 22.6%, p=0.049), even after adjustment for observation time and age at diagnosis (OR 8.1, p=0.047). At immunohistochemistry on 31 JIA samples, higher CD3 expression was described in polyarticular compared with oligoarticular subset (p=0.040). Patients with severe disease course had higher CD20+ rate (OR 7, p=0.023), regardless of JIA subset and treatment exposure.

Conclusions

Synovial tissue analysis might support the clinicians in the diagnostic approach of paediatric patients presenting with arthritis and guide the clinical management in JIA.
Seeking Out the Stakeholders: Building Coalitions to Address Cultural (In)equity through Arts-based, Community-engaged Research
Authors: Wertz Olivia M. , Workman Kandi , Carlson Erin Brock
Published: December 2023

Artists are an important, but under-recognized, aspect of rural community growth. This research article details a collaborative project between a statewide arts organization and academic researchers in West Virginia designed to document the needs of under-represented artists across the state. We share our theoretical approach that meshes stakeholder and standpoint theory and our research approach that uses participatory and arts-based methods such as asset-mapping and collage-based listening sessions. Ultimately, we provide a model for others interested in research projects that explicitly prioritize coalition-building throughout a project and demonstrate how cultural (in)equity shapes multiple facets of community life.