bluuebunny/crossref_metadata_2025 huggingface dataset:
Identify, screen and treat via electronic pathway: a semiautomated approach to retriaging a liver clinic waitlist
Authors: Flanagan Eliza , Pianko Stephen , Ho Cindy , Saxby Edward , Grant Julianne , Bell Sally , Stuart Rhonda , Le Suong
Published: July 2024

Background

Long specialist outpatient waiting lists are a source of clinical risk. Triage assignment is based on subjective assessment of referrals and fails to account for dynamic changes in disease status while patients await clinical review.

Aims

To pilot an innovative triage method using a trifold approach to conduct noninvasive assessment of fibrosis and to determine the feasibility of reflex hepatitis C virus (HCV) polymerase chain reaction (PCR) testing.

Methods

A total of 1006 patients awaiting an initial liver clinic appointment at a tertiary Australian hospital were sent a short message service (SMS) requesting a blood test be completed. The first 60 patients received an SMS only, and the subsequent 946 patients also received a phone call from a Liver Care Guide (LCG), a nonclinician employed to increase patient engagement. Liver fibrosis assessment through noninvasive testing was performed using an aspartate aminotransferase to platelet ratio index (APRI) and fibrosis‐4 (FIB4) score. Patients with an APRI ≥1, FIB4 ≥3.25 or positive HCV PCR were retriaged to Category 1.

Results

Four hundred ninety (49%) patients completed testing and 40 (4%) were triaged to Category 1. Subanalyses demonstrated increased response rates with LCG input (P = 0.012). Retriaged patients had been on the waitlist for a median of 216 days, exceeding initial category recommendations.

Conclusion

This study successfully implemented a semiautomated strategy that prioritises patients with probable advanced liver disease or active HCV, demonstrating enhanced patient engagement with LCG support. It highlights the burden of patients referred for specialist care and the need for innovative strategies for monitoring and objective risk stratification.
A new maximum age observed within the family Labridae, ballan wrasse Labrus bergylta
Authors: Pritchard Calum J. , Stendal Marthe M. R. , Treasurer Jim , Halvorsen Kim T. , Skiftesvik Anne B.
Published: July 2024

Ballan wrasse Labrus bergylta is the largest species of wrasse inhabiting European waters and one of the longest‐living species within the family Labridae. A large specimen was caught off the coast of Skjerjehamn, western Norway (total length = 410 mm; weight = 1274 g). The age of the specimen was determined to be 34 years old based on the analysis of its opercula bones. This specimen establishes a new maximum age for ballan wrasse, 5 years older than the previously observed maximum age.
The evidence from in vitro primary fibroblasts and a randomized, double‐blind, placebo‐controlled clinical trial of tuna collagen peptides intake on skin health
Authors: Morakul Boontida , Teeranachaideekul Veerawat , Wongrakpanich Amaraporn , Leanpolchareanchai Jiraporn
Published: July 2024

Background

Collagen peptides from various sources demonstrate benefits in health and well‐being both in vitro and in clinical trials. However, there is a scarce study of collagen peptides from Tuna on skin health.

Aims

To investigate the impact of collagen peptides derived from Tuna (Katsuwonus pelamis and Thunnus albacares) on skin health, utilizing in vitro biological studies and a randomized controlled trial.

Methods

In vitro biological studies on human dermal primary fibroblasts were evaluated in terms of collagen and elastin synthesis and senescent cell inhibition. A randomized, placebo‐controlled, double‐blind clinical trial was conducted on 72 women who were randomly assigned to receive either tuna collagen peptides (n = 36) or a placebo (n = 36) orally for 8 weeks and 2 weeks post‐ingestion by measuring skin hydration, transepidermal water loss (TEWL), skin elasticity, and skin density.

Results

In vitro biological effects demonstrated dose‐dependent positive results in increasing collagen and elastin synthesis and reducing senescent cells. The effects on collagen and senescent cells plateaued at high concentrations. A clinical trial showed that the test group experienced a significant increase in skin hydration, elasticity, and density, along with a decrease in TEWL compared to the baseline. The test and placebo groups showed statistically significant differences at 8 weeks for all parameters except for the TEWL at the face. All positive effects were substantially retained even after 2 weeks of discontinuation.

Conclusions

These findings demonstrate the significant potential of tuna collagen peptides to promote human skin health, warranting further investigation as a potential nutraceutical.
Contestation over a Profession's Memory: The UK Pharmacy Profession, 1880–1905
Authors: Currie Graeme , Wild Andrew , Lockett Andy
Published: July 2024

We draw on the historical case of the UK pharmacy industry from 1880–1905 to examine how, in the face of a competitive threat to their survival, lower status professionals seek to reinvigorate the memory of their role in providing community service in the public interest. Derived from this, our study reveals how mnemonic work has a nuanced nature in professionalized settings. First, lower status actors enact certain types of mnemonic work because they need to maintain professional purity. Second, to maintain professional purity, lower status professionals also need to carefully sequence their mnemonic work and pay particular attention to the social context within which they are seeking to manipulate collective memory. Our study also shows how, within such a sequencing, for lower status professionals to successfully enact mnemonic work, they need to collectively mobilize their ranks and may engage in entryism to professional bodies dominated by their higher status peers.
Variation in dentist participation between dental medicaid managed care organizations
Authors: Nwachukwu Pamela C. , Damiano Peter C. , Levy Steven , Thomas James C. , Shane Dan , Singhal Astha , Dabdoub Shareef M. , Reynolds Julie C.
Published: July 2024

Objectives

Dentists' Medicaid participation is a critical factor affecting dental care access for Medicaid beneficiaries. An important gap in existing literature is the variation in participation across Medicaid dental Managed Care Organizations (MCOs) in states with more than one. This study examined the variation in participation overall and in predictors of dentist participation between two MCOs in Iowa's Dental Medicaid program.

Methods

Data were obtained from a survey of Iowa private practice dentists (n = 1256). Responding general dentists (n = 497) were included in the final analytic sample. Univariate, bivariate, and multivariable logistic regression analyses were conducted to examine demographic and practice characteristics associated with dentist participation (acceptance of new Medicaid patients) between MCOs and by age category.

Results

Among respondents, the proportions accepting new adults with Medicaid were 26% (MCO 1) and 7% (MCO 2); for children, they were 40% (MCO 1) and 11% (MCO 2). For adults, dentists who were too busy (MCO1) and solo practice dentists (MCO2) were positively significantly associated with the acceptance of new patients. For children, group and rural practice dentists, as well as dentists who worked <32 h/week were positively significantly associated with acceptance of new patients with MCO1.

Conclusions

There was considerable variation in dentist‐reported acceptance of new adult and child Medicaid patients, and in the factors affecting acceptance of new patients between MCOs in Iowa dental Medicaid. Future studies of Medicaid participation should consider variations by MCO in states with more than one dental MCO so as not to miss important factors affecting Medicaid participation.
In Vitro and In Vivo Effects of Melatonin‐Containing Combinations in Human Pancreatic Ductal Adenocarcinoma
Authors: Zeppa Laura , Aguzzi Cristina , Morelli Maria Beatrice , Marinelli Oliviero , Amantini Consuelo , Giangrossi Martina , Santoni Giorgio , Fanelli Alessandro , Luongo Margherita , Nabissi Massimo
Published: July 2024

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis and high mortality rates. Therefore, it is necessary to identify new targets and therapeutic strategies to improve the prognosis of patients with PDAC. Integrative therapies are increasingly being used to boost the efficacy of the known anticancer therapeutic approaches. Hence, this study aimed to evaluate the effects of a novel combination of different potential anticancer molecules, melatonin (MLT), cannabidiol (CBD), and oxygen–ozone (O2/O3) to treat PDAC using in vitro and in vivo models of human PDAC. The effect of this combination was investigated in combination with gemcitabine (GEM), the most common chemotherapeutic drug used for PDAC treatment. The combination of MLT + CBD + O2/O3 was more effective than the individual treatments in inhibiting PDAC cell viability and proliferation, inducing cell death, and modulating the RAS pathway protein levels. Moreover, different combinations of treatments reduced tumor mass in the PDAC mouse model, thus promoting the effect of GEM. In conclusion, a mixture of MLT + CBD + O2/O3 could serve as a potential adjuvant therapeutic strategy for PDAC.
Infection by Crithidia bombi increases relative abundance of Lactobacillus spp. in the gut of Bombus terrestris
Authors: Blasco‐Lavilla Nuria , López‐López Alejandro , De la Rúa Pilar , Barribeau Seth Michael
Published: July 2024

Gut microbial communities confer protection against natural pathogens in important pollinators from the genera Bombus and Apis. In commercial species B. terrestris and B. impatiens, the microbiota increases their resistance to the common and virulent trypanosomatid parasite Crithidia bombi. However, the mechanisms by which gut microorganisms protect the host are still unknown. Here, we test two hypotheses: microbiota protect the host (1) through stimulation of its immune response or protection of the gut epithelium and (2) by competing for resources with the parasite inside the gut. To test them, we reduced the microbiota of workers and then rescued the microbial community by feeding them with microbiota supplements. We then exposed them to an infectious dose of C. bombi and characterised gene expression and gut microbiota composition. We examined the expression of three antimicrobial peptide genes and Mucin‐5AC, a gene with a putative role in gut epithelium protection, using qPCR. Although a protective effect against C. bombi was observed in bumblebees with supplemented microbiota, we did not observe an effect of the microbiota on gene expression that could explain alone the protective effect observed. On the other hand, we found an increased relative abundance of Lactobacillus bacteria within the gut of infected workers and a negative correlation of this genus with Gilliamella and Snodgrassella genera. Therefore, our results point to a displacement of bumblebee endosymbionts by C. bombi that might be caused by competition for space and nutrients between the parasite and the microbiota within the gut.
Factors affecting early neurological deterioration after intravenous alteplase treatment for branch atheromatous disease
Authors: Mizuno Satoko , Deguchi Ichiro , Takahashi Shinichi , Arai Noriko , Nakagami Toru , Kimura Ryutaro , Oryu Kiichiro , Watanabe Kaito , Ueda Sae , Fujiwara Shinako , Kato Yuji , Hayashi Takeshi , Suda Satoshi
Published: July 2024

Background

Intravenous alteplase treatment is effective for acute cerebral infarction, irrespective of the stroke type. However, its value for branch atheromatous disease (BAD) remains unclear, and early neurological deterioration (END) can occur.

Aim

To investigate factors affecting END after intravenous alteplase treatment in patients with acute BAD.

Methods

This study included 40 consecutive patients diagnosed with cerebral infarction due to BAD in the lenticulostriate artery territory and treated with intravenous alteplase between April 2007 and March 2023. END was defined as an increase of ≥2 points in the total National Institutes of Health Stroke Scale score or ≥1 point in the motor items within 24 h post‐alteplase administration compared to the score at admission. Factors affecting END were retrospectively evaluated.

Results

END was observed in 17 of the 40 patients (43%). The median time from the start of alteplase administration to the worsening of neurologic symptoms was 5 h. After intravenous alteplase treatment, the END group had a significantly lower 24‐h average systolic blood pressure (SBP, mean ± standard deviation mmHg) than the non‐END group (142.0 ± 15.2 vs. 149.4 ± 12.0, p < 0.001). The SBP at each time point (immediately before alteplase administration and every 2 h up to 24 h after alteplase administration) was significantly lower in the END than in the non‐END group at 2, 4, and 6 h after alteplase administration.

Conclusions

When intravenous alteplase was administered for BAD, BP control after alteplase administration affected END. When alteplase is administered for BAD, it is important to control the blood pressure to maintain hemodynamics.
Hydraulic plasticity and water use regulation act to maintain the hydraulic safety margins of Mediterranean trees in rainfall exclusion experiments
Authors: Moreno Myriam , Limousin Jean‐Marc , Simioni Guillaume , Badel Eric , Rodríguez‐Calcerrada Jesus , Cochard Hervé , Torres‐Ruiz José M. , Dupuy Jean‐Luc , Ruffault Julien , Ormeno Elena , Delzon Sylvain , Fernandez Catherine , Ourcival Jean‐Marc , Martin‐StPaul Nicolas
Published: July 2024

Hydraulic failure due to xylem embolism has been identified as one of the main mechanisms involved in drought‐induced forest decline. Trees vulnerability to hydraulic failure depends on their hydraulic safety margin (HSM). While it has been shown that HSM globally converges between tree species and biomes, there is still limited knowledge regarding how HSM can adjust locally to varying drought conditions within species. In this study, we relied on three long‐term partial rainfall exclusion experiments to investigate the plasticity of hydraulic traits and HSM for three Mediterranean tree species (Quercus ilex L., Quercus pubescens Willd., and Pinus halepensis Mill.). For all species, a homeostasis of HSM in response to rainfall reduction was found, achieved through different mechanisms. For Q. ilex, the convergence in HSM is attributed to the adjustment of both the turgor loss point (Ψtlp) and the water potential at which 50% of xylem conductivity is lost due to embolism (P50). In contrast, the maintenance of HSM for P. halepensis and Q. pubescens is related to its isohydric behavior for the first and leaf area adjustment for the latter. It remains to be seen whether this HSM homeostasis can be generalized and if it will be sufficient to withstand extreme droughts expected in the Mediterranean region.
The burden in family caregivers of people living with dementia: prevalence and predictors
Authors: Aljezawi Ma'en , Kofahi Raid , Abu Khait Abdallah , Abdalrahim Asem , Al Omari Omar , Alkhawaldeh Abdullah , ALBashtawy Mohammed , Suliman Mohammad , Khader Imad Abu , Jallad Mohammed , Qaddumi Jamal , ALBashtawy Zaid , Hani Salam Bani
Published: July 2024

Background

Providing care for people with dementia incorporates a level of burden which can affect quality of life for both the caregiver and the recipient of care. This study measures the level of burden experienced by Jordanian caregivers for people with dementia and explore related predictors.

Methods

Through a cross‐sectional survey, participants were invited through convenience sampling to participate in a structured interview.

Results

A total of 406 participants completed the survey. According to Zarit Burden Interview, the mean burden score of the sample was 26.2 (SD = 16.2). This score falls under the mild to moderate burden level. Older age of the patient, severe dementia, lower number of caregivers, if the caregiving negatively affected family relations, and if the caregiving negatively affected jobs, were significant predictors of burden.

Conclusion

Caregivers in the current study reported no burden to a minimum burden. This result does not mean that these caregivers have no or minimal stress or that they do not have psychological needs; on the contrary, these results call for more attention to providing extra psychological and emotional support to caregivers of patients with dementia in order to decrease the burden level and maintain their efforts in caregiving. Future studies are required to discern the shape and context of unmet caregiver needs, assessment, and support.
Osteopontin expression in dromedary camel's conceptuses during the peri‐implantation period
Authors: Moqbel Mohammed Salem , Alhaider Abdulraman Khalid , Almathen Faisal , Amor Nidhal Neji Ben , Al‐Ramadan Saeed Yaseen
Published: July 2024

The reproductive efficiency of dromedary camels is hindered by challenges such as early embryonic mortality, which may be attributed to a lack of synchronization between conceptus signalling and uterine receptivity. Understanding the intricate biological processes involved in feto‐maternal interactions during implantation is crucial to address these limitations. Osteopontin (OPN) is a protein involved in cell signalling and adhesion, playing a crucial role in embryonic implantation. Previous studies have shown the presence of OPN in the uterine endometrium of various mammalian species including dromedary camels. However, the expression pattern of OPN in dromedary conceptuses remains unexplored. Thus, the current study aimed, for the first time, to investigate the temporospatial expression of OPN in dromedary conceptuses during the peri‐implantation period at Days 8, 10, and 12 of pregnancy. Twelve conceptuses were recovered non‐surgically from pregnant females on Days 8, 10, 12 of pregnancy. Quantitative real‐time PCR (qrt‐PCR), immunohistochemistry (IHC), and immunofluorescence (IF) were employed for analysis of the expression of OPN mRNA and protein. The results revealed significant increases in both OPN mRNA and protein expression started on Day 10 and peaked at Day 12 of pregnancy. Immuno‐localization confirmed the presence of OPN protein in the trophectoderm and endoderm of dromedary conceptuses. In conclusion, the expression and localization of OPN during the peri‐implantation period in dromedary conceptuses imply its involvement as a crucial reproductive factor and its upregulation during this period, with a pronounced increase close to attachment time (Day 12 of pregnancy) further supports its role in embryo adhesion, implantation, and placentation.
Trusting organizational law
Authors: Bayern Shawn
Published: July 2024

Decentralized governance technologies like blockchains are often proposed as substitutes for private legal arrangements like those provided by company law or organizational law more generally. In established legal systems in developed countries, the costs of implementing such algorithmic mechanisms are likely to be greater than the agency or other costs that come from selecting and trusting an existing third party. But even if that were not true, attempting to achieve decentralized governance solely by algorithm is more complicated than it appears and incurs significant “formalism costs.” Such costs can be reduced by the wealth of experience represented by the operational processes of organizational law. Mixing those operational processes with algorithmic governance by “opting into” organizational law, thereby letting it govern the interface between the algorithms and the real‐world legal rights associated with an organization, is likely to be a governance model superior to the use of algorithmic governance alone.
Effects of poly‐γ‐glutamic acid addition on the transformation and distribution of soil nitrogen under different water conditions
Authors: Jing Bo , Shi Wenjuan , Wang Ying , Zhai Zhongmin , Chen Tao
Published: July 2024

The impact of external poly‐γ‐glutamic acid (γ‐PGA) on soil nitrogen (N) transformation and distribution remains unclear, despite its contrasting effects on N use efficiency. Therefore, soil culture and soil column experiments were conducted using three different γ‐PGA addition rates (0%, 4% and 8% of dry soil weight, w/w) under different soil water contents (40%, 60% and 80% of field water capacity) and dry–wet cycles (0, 2, 4 and 8 times cycles; a single dry–wet cycle involved reducing soil water content from 80% to 40% of field water capacity) in sandy loam soil. The results of soil culture experiment showed that the γ‐PGA significantly increased soil –N and –N contents, as well as nitrification and transformation rates. However, these effects were observed to be influenced by both the culture time and soil water content. In addition, the results of soil column experiment showed that γ‐PGA not only significantly enhanced the soil inorganic nitrogen content within the 0–20 cm soil layer, but also improved water retention capacity. However, the differences between the γ‐PGA treatments gradually diminished with an increase in dry–wet cycle times. These results indicate that γ‐PGA addition enhanced soil inorganic N content and soil water retention by influencing soil N transformation and water distribution. However, the impact of γ‐PGA addition on soil improvement was regulated by soil water content, which should be taken into full consideration in agricultural practices.
Explicit continued fraction expansion of a rational root of 1+x−1$1+x^{-1}$ over Fp$\mathbb {F}_p$
Authors: Bugeaud Yann , Han Guo‐Niu
Published: July 2024

Let be a prime number, and positive integers coprime with . We provide the explicit continued fraction expansion of the th root of in the power series field . We determine its irrationality exponent.
Influence of Elements in Steel With Anode Plasma Electrolytic Boriding on Hardness Gradient and Tribological Properties
Authors: Tianlin Zhu , Chongyang Nie , Chao Zhao , Lixia Ying , Guixiang Wang , Wei Wu , Ting Zheng , Yan Lu
Published: July 2024

The influence of elements in steel on anode plasma electrolytic boriding has been studied. The modified layers and surfaces on steel samples were analyzed by a scanning electron microscope, an X-ray diffractometer, a surface profiler, a microhardness tester, and a ball-disc tribometer. With 1045 steel as the control group, the same treatment parameters (treatment with 5 min, 200 V of voltage, 5% boric acid, and 10% ammonium chloride) were implemented on various steel substrates. It was found that a low content of carbon would hinder the penetration of boron, and other metallic elements can improve the mircrohardness gradient and decrease the wear-rate. Chromium and manganese can increase the maximum microhardness than treated 1045 by about 15%, but have a detrimental effect on surface flatness. Nevertheless, manganese has the ability to rapidly create a layer of oxide that enhances the tribological characteristics, leading to a remarkably low average friction coefficient of 0.26 for 1046 steel. The presence of molybdenum in the element composition of 4140 steel results in a notable enhancement of surface properties, namely in terms of wear resistance, with a minimum wear-rate 2.1 × 10−6 g/Nm for 4140 steel. Nickel does not appear to have a notable impact on the surface characteristics of the modified samples.
How does the polymerase of non-segmented negative strand RNA viruses commit to transcription or genome replication?
Authors: Kleiner Victoria A. , Fearns Rachel
Published: July 2024

The
Mononegavirales
, or non-segmented negative-sense RNA viruses (nsNSVs), includes significant human pathogens, such as respiratory syncytial virus, parainfluenza virus, measles virus, Ebola virus, and rabies virus. Although these viruses differ widely in their pathogenic properties, they are united by each having a genome consisting of a single strand of negative-sense RNA. Consistent with their shared genome structure, the nsNSVs have evolved similar ways to transcribe their genome into mRNAs and replicate it to produce new genomes. Importantly, both mRNA transcription and genome replication are performed by a single virus-encoded polymerase. A fundamental and intriguing question is: how does the nsNSV polymerase commit to being either an mRNA transcriptase or a replicase? The polymerase must become committed to one process or the other either before it interacts with the genome template or in its initial interactions with the promoter sequence at the 3´ end of the genomic RNA. This review examines the biochemical, molecular biology, and structural biology data regarding the first steps of transcription and RNA replication that have been gathered over several decades for different families of nsNSVs. These findings are discussed in relation to possible models that could explain how an nsNSV polymerase initiates and commits to either transcription or genome replication.
rAAV expressing a COBRA-designed influenza hemagglutinin generates a protective and durable adaptive immune response with a single dose
Authors: Wiggins Kristin B. , Winston Stephen M. , Reeves Isaiah L. , Gaevert Jessica , Spence Yunyu , Brimble Mark A. , Livingston Brandi , Morton Christopher L. , Thomas Paul G. , Sant Andrea J. , Ross Ted M. , Davidoff Andrew M. , Schultz-Cherry Stacey
Published: July 2024

Influenza remains a worldwide public health threat. Although seasonal influenza vaccines are currently the best means of preventing severe disease, the standard-of-care vaccines require frequent updating due to antigenic drift and can have low efficacy, particularly in vulnerable populations. Here, we demonstrate that a single administration of a recombinant adenovirus-associated virus (rAAV) vector expressing a computationally optimized broadly reactive antigen (COBRA)-derived influenza H1 hemagglutinin (HA) induces strongly neutralizing and broadly protective antibodies in naïve mice and ferrets with pre-existing influenza immunity. Following a lethal viral challenge, the rAAV-COBRA vaccine allowed for significantly reduced viral loads in the upper and lower respiratory tracts and complete protection from morbidity and mortality that lasted for at least 5 months post-vaccination. We observed no signs of antibody waning during this study. CpG motif enrichment of the antigen can act as an internal adjuvant to further enhance the immune responses to allow for lower vaccine dosages with the induction of unique interferon-producing CD4+ and CD8+ T cells specific to HA head and stem peptide sequences. Our studies highlight the utility of rAAV as an effective platform to improve seasonal influenza vaccines.

IMPORTANCE

Developing an improved seasonal influenza vaccine remains an ambitious goal of researchers and clinicians alike. With influenza routinely causing severe epidemics with the potential to rise to pandemic levels, it is critical to create an effective, broadly protective, and durable vaccine to improve public health worldwide. As a potential solution, we created a rAAV viral vector expressing a COBRA-optimized influenza hemagglutinin antigen with modestly enriched CpG motifs to evoke a robust and long-lasting immune response after a single intramuscular dose without needing boosts or adjuvants. Importantly, the rAAV vaccine boosted antibody breadth to future strains in ferrets with pre-existing influenza immunity. Together, our data support further investigation into the utility of viral vectors as a potential avenue to improve our seasonal influenza vaccines.
Both middle and large envelope proteins can mediate neutralization of hepatitis B virus infectivity by anti-preS2 antibodies: escape by naturally occurring preS2 deletions
Authors: Zhang Jing , Wang Qianru , Yuan Wenqing , Li Jing , Yuan Quan , Zhang Jiming , Xia Ningshao , Wang Yongxiang , Li Jisu , Tong Shuping
Published: July 2024

Hepatitis B virus (HBV) expresses co-terminal large (L), middle (M), and small (S) envelope proteins containing preS1/preS2/S, preS2/S, and S domain alone, respectively. S and preS1 domains mediate sequential virion attachment to heparan sulfate proteoglycans and sodium taurocholate cotransporting polypeptide (NTCP), respectively, which can be blocked by anti-S and anti-preS1 antibodies. How anti-preS2 antibodies neutralize HBV infectivity remains enigmatic. The late stage of chronic HBV infection often selects for mutated preS2 translation initiation codon to prevent M protein expression, or in-frame preS2 deletions to shorten both L and M proteins. When introduced to infectious clone of genotype C or D, both M-minus mutations and most 5’ preS2 deletions sustained virion production. Such mutant progeny viral particles were infectious in NTCP-reconstituted HepG2 cells. Neutralization experiments were performed on the genotype D clone. Although remaining susceptible to anti-preS1 and anti-S neutralizing antibodies, M-minus mutants were only partially neutralized by two anti-preS2 antibodies tested while preS2 deletion mutants were resistant. By infection experiments using viral particles with lost versus increased M protein expression, or a neutralization escaping preS2 deletion only present on L or M protein, we found that both full-length L and M proteins contributed to virus neutralization by the two anti-preS2 antibodies. Thus, immune escape could be a driving force for the selection of M-minus mutations, and especially preS2 deletions. The fact that both L and M proteins could mediate neutralization by anti-preS2 antibodies may shed light on the underlying molecular mechanism.

IMPORTANCE

The large (L), middle (M), and small (S) envelope proteins of hepatitis B virus (HBV) contain preS1/preS2/S, preS2/S, and S domain alone, respectively. The discovery of heparan sulfate proteoglycans and sodium taurocholate cotransporting polypeptide (NTCP) as the low- and high-affinity HBV receptors could explain neutralizing potential of anti-S and anti-preS1 antibodies, respectively, but how anti-preS2 neutralizing antibodies work remains enigmatic. In this study, we found two M-minus mutants in the context of genotype D partially escaped two anti-preS2 neutralizing antibodies in NTCP-reconstituted HepG2 cells, while several naturally occurring preS2 deletion mutants escaped both antibodies. By point mutations to eliminate or enhance M protein expression, and by introducing preS2 deletion selectively to L or M protein, we found binding of anti-preS2 antibodies to both L and M proteins contributed to neutralization of wild-type HBV infectivity. Our finding may shed light on the possible mechanism(s) whereby anti-preS2 antibodies neutralize HBV infectivity.
The structural setting and evolution of the Upper Beaver gold–copper deposit, Ontario, Canada
Authors: Orlóci-Goodison Ruth A. , Lafrance Bruno , Beaudoin Georges , Côté-Mantha Olivier
Published: July 2024

The ca. 2680 Ma Upper Beaver deposit is an Archean intrusion-related gold–copper deposit located in the Abitibi greenstone belt, Ontario. The deposit is associated with the Upper Beaver Intrusive Complex, which was emplaced in the hanging wall of an extensional listric fault rooted in metavolcanic rocks of the ca. 2704–2695 Ma Blake River assemblage. The fault formed during the development of an overlying basin of fluvial metasedimentary and alkalic metavolcanic rocks of the ca. 2679–2669 Ma Timiskaming assemblage. The Upper Beaver deposit was subsequently rotated to its current position during the formation of a post-Timiskaming fold, the Spectacle Lakes Anticline, associated with the development of the Larder Lake–Cadillac deformation zone, located 7 km south of the deposit. The Upper Beaver deposit is overprinted by the axial planar cleavage of the anticline but is less deformed than other gold deposits located along the deformation zone. Alteration and other pre-existing planar anisotropies enhanced strain partitioning and the development of folds and fabrics in strained mineralized zones of the deposit. Steeply dipping, sericite-altered mineralized zones developed a continuous foliation surrounding boudinaged and recrystallized quartz–calcite–anhydrite veins, whereas strong, shallowly dipping, stratiform, and skarnoid mineralized zones developed a wavy disjunctive cleavage and deformed mainly by folding. The mineralized zones acted as pre-existing anisotropies during deformation and their orientation and composition were key factors in the development of structures at the Upper Beaver deposit, which can be used as a guide for interpreting the development of structures in similar but more complexly deformed deposits along major deformation zones.
Association of IL‐8 and CXCR2 with AST/ALT Ratio in Liver Abnormalities Screening during Oxidative Stress Injury Caused by VCM
Authors: Dong Yiwen , Wang Xingang , Hu Weijiang , Wang Xin , Bian Hongying , Zhang Wencui , Feng Han  , Kang Ning , Zhang Lin , Ye Meng
Published: July 2024

Liver impairment caused by VCM has been linked to irreversible damage such as fibrosis, necrosis, hepatocellular carcinoma, and liver angiosarcoma. However, the ability to detect abnormalities during initial phase have not been achieved so far. Thus, this study aimed to investigate the effect of interleukin 8 (IL‐8) and C‐X‐C chemokines 2 (CXCR2) on screening for a VCM‐exposed group (n = 227) from a PVC manufacturing factory compared to a control group (n = 110) in Tianjin City in 2020 with influence factors evaluation. Ambient concentrations of VCM and health archives from 2012 to 2018 were collected for establishing the dose‐effect trend. A cross‐sectional survey in 2020 was performed to measure TDGA, IL‐8, CXCR2, 8‐OHdG, SOD, GPX, CAT, MDA, and ROS levels. Results indicated a continuous increased incidence on liver abnormalities despite a fluctuated downward trend in cumulative time‐weighted average (CTWA) VCM concentrations over the years. ALT, AST, and AST/ALT ratio all contributed to liver abnormalities that contained fatty liver, liver calcification, and liver cysts, IL‐8 and CXCR2 correlated with each other strongly and showed significant associations with oxidative stress markers, even AST/ALT ratio. IL‐8 (>1547 µg/m3) or CXCR2 (<139 µg/m3) influenced the AST/ALT ratio through reciprocal interactions under oxidative stress injury, CXCR2 (>222 µg/m3), working years of 21 to 30 (a) and 11 to 20 (a), TDGA (>1.52 mg/L), alcohol consumption, smoking habit, and a less sleeping duration of <4 h per day would also be potential factors affecting the AST/ALT ratio. In conclusion (1) even with decreased VCM concentrations in PVC manufacturing factories liver abnormalities that contained fatty liver, liver calcification, and liver cysts could still occur due to oxidative stress injury with involvement of IL‐8 and CXCR2. The status of protective measure and appropriate mask types also play a role; (2) the AST/ALT ratio could be a specific indicator for detecting abnormalities when combined with liver B ultrasonography results before impairment altered from bad to worse; and (3) factors such as definite medication history, fully broken protective facilities, alcohol consumption, less sleeping duration, inappropriate mask types, and longer working years could also influence AST/ALT ratio alterations through complex interactions.
Anti‐Inflammatory and Antioxidant Properties of a New Mixture of Vitamin C, Collagen Peptides, Resveratrol, and Astaxanthin in Tenocytes: Molecular Basis for Future Applications in Tendinopathies
Authors: Marzagalli Monica , Battaglia Stefania , Raimondi Michela , Fontana Fabrizio , Cozzi Marco , Ranieri Francesca R. , Sacchi Roberto , Curti Valeria , Limonta Patrizia
Published: July 2024

Tendinopathy is one of the most frequent musculoskeletal disorders characterized by sustained tissue inflammation and oxidative stress, accompanied by extracellular matrix remodeling. Patients suffering from this pathology frequently experience pain, swelling, stiffness, and muscle weakness. Current pharmacological interventions are based on nonsteroidal anti‐inflammatory drugs; however, the effectiveness of these strategies remains ambiguous. Accumulating evidence supports that oral supplementation of natural compounds can provide preventive, and possibly curative, effects. Vitamin C (Vit C), collagen peptides (Coll), resveratrol (Res), and astaxanthin (Asx) were reported to be endowed with potential beneficial effects based on their anti‐inflammatory and antioxidant activities. Here, we analyzed the efficacy of a novel combination of these compounds (Mix) in counteracting proinflammatory (IL‐1β) and prooxidant (H2O2) stimuli in human tenocytes. We demonstrated that Mix significantly impairs IL‐6‐induced IL‐1β secretion, NF‐κB nuclear translocation, and MMP‐2 production; notably, a synergistic effect of Mix over the single compounds could be observed. Moreover, Mix was able to significantly counteract H2O2‐triggered ROS production. Together, these results point out that Mix, a novel combination of Vit C, Coll, Resv, and Asx, significantly impairs proinflammatory and prooxidant stimuli in tenocytes, mechanisms that contribute to the onset of tendinopathies.
Experimental and Theoretical Investigations on the Use of Pumpkin Peel as a Sustainable Biomass Anticorrosion Agent for Aluminum in HCl Solutions
Authors: Alghamdi Reem D. , Alqarni Laila S. , Alghamdi Maha D. , Alotaibi N. F. , Gadow Hend
Published: July 2024

The sustainable plant‐derived biomass are now understood to be important sources for the prevention of corrosion in metallic alloys. This study examined the effect of a potential novel low‐cost, low‐toxicity inhibitor utilizing pumpkin peel extract (PPE) on aluminum corrosion hydrochloric acid 1M HCl medium. Several experimental methods were used to investigate the inhibitor effect of PPE which include, AFM‐XPS surface analysis, electrochemical studies (electrochemical impedance spectroscopy‐electrochemical frequency modulation‐potentiodynamics), and weight loss procedures. According to the weight loss results, when PPE is introduced to a 1M HCl solution, the inhibitory performance rises up to 95.42% with an increase in PPE concentration in the range of 0–300 ppm at 25°C. Potentiodynamic results showed the investigated PPE inhibitor is a mixed‐type inhibitor. Corrosion inhibition at different temperatures was also examined, and the thermodynamic activation parameters were identified. It was found that the adsorption of the inhibitor on the aluminum followed the Langmuir and kinetic isotherm models. Quantum chemical indices contributed to a greater comprehension of the inhibitory mechanism. To investigate the configurational adsorption performance of the investigated PPE on the aluminum surface, molecular dynamics (MD) simulations were carried out.
Combined Treatment of Uterine Arteriovenous Malformation Using a 16 Fr Miniresectoscope in an Office Setting Without Anesthesia: A Case Report
Authors: Lipari Giovanni , Messina Alessandro , Teston Carolina , Alessi Paolo , Mariani Alessia , Bruno Tiziana , Florio Fernanda , Vegro Sofia , Leo Livio , Masturzo Bianca
Published: July 2024

Arteriovenous malformations (AVMs) are abnormal connections between arteries and veins that bypass the capillary system. Among AVMs, uterine ones are very rare, and it is not possible to have clear data on their incidence, as a good part of the patients remain clinically asymptomatic. Uterine AVMs consist of abnormal communications between branches of the uterine artery and the myometrial venous plexus. They can lead to significant bleeding, resulting in severe anemia and the need for transfusions. Both medical and surgical therapeutic approaches are described in the literature; as regards surgical treatments, the hysteroscopic excision of the endometrial mass represents a conservative and minimally invasive approach. However, there are no reported cases in the literature of AVMs treated using a hysteroscopic approach under local anesthesia and in an office setting. In this article, we propose the case of a young woman diagnosed with postpartum uterine AVM, treated using a 16 Fr miniresectoscope (GUBBINI system; Tontarra Medizintechnik®, Tuttlingen, Germany) in an office setting with a pain control protocol (pericervical infiltration and nitrous oxide via bucconasal mask). No complications occurred, and the woman was discharged immediately after the procedure. Finally, the patient was asked how tolerable and acceptable the procedure was compared to expectations; the woman defined the procedure as very bearable and well tolerated. The outpatient treatment, with an adequate pain control protocol, proved to be less invasive for the woman, did not require narcosis and hospital admission, but was equally therapeutic and effective compared to the treatment performed in the operating room.
Table S2 from E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network
Authors: Poliaková Turan Michaela , Riedo Rahel , Medo Matúš , Pozzato Chiara , Friese-Hamim Manja , Koch Jonas P. , Coggins Si’Ana A. , Li Qun , Kim Baek , Albers Joachim , Aebersold Daniel M. , Zamboni Nicola , Zimmer Yitzhak , Medová Michaela
Published: July 2024

Differential expression analysis of the GTL-16 and EBC-1 transcriptomics data.
Figure 6 from E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network
Authors: Poliaková Turan Michaela , Riedo Rahel , Medo Matúš , Pozzato Chiara , Friese-Hamim Manja , Koch Jonas P. , Coggins Si’Ana A. , Li Qun , Kim Baek , Albers Joachim , Aebersold Daniel M. , Zamboni Nicola , Zimmer Yitzhak , Medová Michaela
Published: July 2024

Survival analysis focused on the MET-E2F1-purine synthesis axis in clinical samples of TCGA cancer cohorts. Samples are differentiated by the under- and overexpression of individual transcripts. A, Impact of E2F1 and MET mRNA co-expression on survival of patients with lung, head and neck, stomach, and colorectal cancers. MET low/high percentiles 33/67. B, Impact of the mRNA co-expression of MET and GART/purine synthesis pathway-related enzymes on survival of patients with lung cancer. MET low/high percentiles 25/75. C, Impact of MET and RNR subunit (RRM1 and RRM2) mRNA co-expression on survival of patients with lung cancer. MET low/high percentiles 25/75.
Figure S4 from N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma
Authors: Geroyska Sofia , Mejia Isabel , Chan Alfred A. , Navarrete Marian , Pandey Vijaya , Kharpatin Samuel , Noguti Juliana , Wang Feng , Srole Daniel , Chou Tsui-Fen , Wohlschlegel James , Nemeth Elizabeta , Damoiseaux Robert , Shackelford David B. , Lee Delphine J. , Díaz Begoña
Published: July 2024

Inhibition of NMT increases mitochondrial ferrous iron content in (KL/K)MUT but not (KL/K)WT lung carcinoma cells.
Characteristics and Clinical Significance of Atopy in Chronic Spontaneous Urticaria: A Cross-Sectional Observational Study
Authors: Chen Qiquan , Wang Wenwen , Yang Xianjie , Li Shifei , Deng Sisi , Wang Huan , Liu Wenying , Ni Bing , Song Zhiqiang
Published: July 2024

Introduction: Atopy is an important and non-negligible clinical phenomenon in chronic spontaneous urticaria (CSU). However, the characteristics and clinical significance of atopy in patients with CSU have not been fully described. This study aimed to analyze the characteristics and clinical significance of atopy in patients with CSU. Methods: A descriptive cross-sectional design was used. The study enrolled 176 patients with CSU. All enrolled patients underwent total IgE, specific IgE, and autologous serum skin tests (ASSTs). The relationships between atopy, the demographic and clinical data of patients with CSU, and the response to ASST were analyzed in detail; the distribution of allergens in atopic CSU was also analyzed. Results: Atopy was confirmed in 48.9% of patients with CSU. Patients with atopic CSU were more likely than patients with non-atopic CSU to have dermatographism (57.0% vs. 41.1%, p < 0.05), history of urticaria (37.2% and 18.9%, respectively; p < 0.01), angioedema (39.5% and 24.4%, respectively; p < 0.05), and anaphylaxis (7/86 and 1/90, respectively; p < 0.05). Atopy was not associated with ASST response, disease duration, or response to antihistamine treatment in patients with CSU, nor was it associated with the urticaria activity score (UAS7), chronic urticaria quality of life questionnaire (CU-Q2oL), or pruritus visual analog scale (VAS) scores (all p < 0.05). The most common allergen in patients with atopic CSU was dust mites, followed by animal food allergens, tree/grass pollen, and cockroaches. Conclusions: Although larger prospective studies are needed to confirm these results, our study found atopy occurred in nearly half of patients with CSU, and preliminarily links atopy to CSU, suggesting it as a potential risk factor for angioedema, anaphylaxis, and recurrent urticaria, mirroring allergen patterns in other allergic disease.
Clinical Outcomes of a New Monofocal Intraocular Lens in Patients Undergoing Phacovitrectomy for Idiopathic Epiretinal Membrane
Authors: Jukić Tomislav , Bajraktari Gentian , Vukojević Nenad , Oroz Martin , Radolović Andrea , Mandić Krešimir , Kalauz Miro
Published: July 2024

Introduction: The purpose of this study was to evaluate the clinical outcomes and quality of life of newly generated monofocal intraocular lens (IOL) in patients diagnosed with idiopathic epiretinal membrane (IEM) following phacovitrectomy. Methods: In this prospective study, 42 patients with IEM and cataract underwent pars plana vitrectomy. They were divided into the ICB00 group (21 patients) and the ZCB00 group (21 patients). Data collected before and after the surgery were compared between the two groups, including uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), vision-related quality of life (VRQOL), intraocular pressure, contrast sensitivity (CS), and central macular thickness (CMT). Results: The preoperative characteristics of the two groups showed no significant differences. However, at the 6-month follow-up after surgery, there were significant improvements in UDVA (p < 0.001), UIVA (p < 0.001), VRQOL (p < 0.001), CS (p < 0.001), and CMT (p < 0.001) compared to baseline. Notably, the Eyhance ICB00 group showed a significantly higher UCIVA value at 6 months post-surgery when compared to the Tecnis ZCB00 group (p = 0.001), while other parameters did not show significant differences between the groups. Conclusion: The Eyhance IOL significantly improved both intermediate and distance visual acuity, with no notable difference in quality of life or CS compared to the Tecnis ZCB00 IOL after IEM removal. It appears to be a favorable choice for combined cataract and vitreoretinal surgery, offering enhanced vision for daily tasks and a promising alternative to traditional monofocal IOLs.
A Cautionary Tale for Polycentric Climate Governance: Sweden’s Roles in Orchestrating Decarbonization
Authors: Widerberg Oscar , Bäckstrand Karin , Lövbrand Eva , Marquardt Jens , Nasiritousi Naghmeh
Published: July 2024

The Paris Agreement ushered in an era of climate governance underpinned by a polycentric theory of change, emphasizing experimentation, collaboration, and innovation while downplaying political contestation, power asymmetries, and the need for regulatory action by the state. This article explores the roles the state plays in polycentric climate governance, focusing on the tension between the regulatory state, where authorities set, monitor, and enforce rules, and the orchestrating state, which facilitates collaboration with nonstate actors to induce behavioral change. Using decarbonization in Sweden as an illustrative case study, the article synthesizes the results of two research projects evaluating the promises and limits of polycentric climate governance. The results problematize the view that Sweden is a forerunner in climate governance, suggesting that while the Swedish government has mobilized support from important industries and cities in favor of decarbonization, that support may be insufficient to achieve necessary societal transformation for deep decarbonization. Finally, the study reflects on the conditions necessary for polycentric governance to effectively decarbonize society, highlighting the pivotal role of the regulatory state.