bluuebunny/crossref_metadata_2025 huggingface dataset:
Mosaic HIV-1 vaccination induces anti-viral CD8
+
T cell functionality in the phase 1/2a clinical trial APPROACH
Authors: van Duijn Janine , Stieh Daniel , Fernandez Natalia , King Deborah , Gilmour Jill , Tolboom Jeroen , Callewaert Katleen , Willems Wouter , Pau Maria G. , De Rosa Stephen C. , McElrath M. Juliana , Barouch Dan H. , Hayes Peter
Published: October 2023

The ability of vaccine-induced T cells to inhibit viral replication may contribute to protect against human immunodeficiency virus (HIV) acquisition. Here, we tested
ex vivo
viral inhibitory activity of T cell responses induced by a multivalent HIV vaccine based on the replication-incompetent recombinant adenovirus serotype 26 vector with a mosaic immunogen strategy (Ad26.Mos.HIV), designed for broad immune coverage of diverse HIV-1 strains. Using clinical trial samples with a diverse range of T cell responses measured by IFN-γ ELISpot, anti-viral function of vaccine-induced CD8+ T cells was assessed by inhibition of HIV-1 replication in autologous CD4+ T cells to a panel of HIV-1 isolates.
Ex vivo
expanded CD8+ T cells were able to inhibit replication of HIV in autologous CD4+ T cells, with 94% of vaccinees inhibiting at least one out of eight HIV isolates, and a median of 5 isolates inhibited at peak immunogenicity. Correlations between viral inhibition and ICS as well as ELISpot responses were explored, demonstrating positive correlations. Broad ELISpot responsiveness to different regions of the Env, Gag, and Pol proteins was associated with breadth of viral inhibitory responses. Moreover, polyfunctionality of CD8+ T cells correlated well with viral inhibition. These findings indicate that functional immunological breadth as well as antigenic breadth is important to induce antiviral activity. This study advances the understanding of vaccine-induced T cell functionality and demonstrates for the first time that Ad26.Mos.HIV vaccination in combination with adjuvanted gp140 can induce broad viral inhibitory activity toward a panel of diverse HIV-1 clades.

IMPORTANCE

The functionality of CD8+ T cells against human immunodeficiency virus-1 (HIV-1) antigens is indicative of HIV-progression in both animal models and people living with HIV. It is, therefore, of interest to assess CD8+ T cell responses in a prophylactic vaccination setting, as this may be an important component of the immune system that inhibits HIV-1 replication. T cell responses induced by the adenovirus serotype 26 (Ad26) mosaic vaccine regimen were assessed previously by IFN-γ ELISpot and flow cytometric assays, yet these assays only measure cytokine production but not the capacity of CD8+ T cells to inhibit replication of HIV-1. In this study, we demonstrate direct anti-viral function of the clinical Ad26 mosaic vaccine regimen through
ex vivo
inhibition of replication of diverse clades of HIV-1 isolates in the participant’s own CD4+ T cells.
Whole genome structural predictions reveal hidden diversity in putative oxidative enzymes of the lignocellulose-degrading ascomycete
Parascedosporium putredinis
NO1
Authors: Scott Conor J. R. , Leadbeater Daniel R. , Oates Nicola C. , James Sally R. , Newling Katherine , Li Yi , McGregor Nicholas G. S. , Bird Susannah , Bruce Neil C.
Published: October 2023

Economic valorization of lignocellulose is paramount to realizing a true circular bioeconomy; however, this requires the development of systems and processes to expand the repertoire of bioproducts beyond current renewable fuels, chemicals, and sustainable materials.
Parascedosporium putredinis
NO1 is an ascomycete that thrived at the later stages of a wheat-straw composting community culture, indicating a propensity to degrade recalcitrant lignin-enriched biomass, but exists within an underrepresented and underexplored fungal lineage. This strain has been proven to be an exciting candidate for the identification of new enzymes targeting recalcitrant components of lignocellulose following the recent discovery of a new lignin β-ether linkage cleaving enzyme. The first genome for the genus
Parascedosporium
for
P. putredinis
NO1 genome was sequenced, assembled, and annotated. The genome is 39 Mb in size, consisting of 21 contigs annotated to contain 9.998 protein-coding sequences. The carbohydrate-active enzyme (CAZyme) repertoire was compared to 2570 ascomycete genomes and in detail with
Trichoderma reesei
,
Fusarium oxysporum
, and sister taxa
Scedosporium boydii
. Significant expansion in the oxidative auxiliary activity class of CAZymes was observed in the
P. putredinis
NO1 genome, resulting from increased sequences encoding putative lytic polysaccharide monooxygenases (LPMOs), oxidative enzymes acting within LPMO redox systems, and lignin-degrading laccases.
P. putredinis
NO1 scored above the 95th percentile for AA gene density across the ascomycete phylum, suggesting a primarily oxidative strategy for lignocellulose breakdown. Novel structure-based searching approaches were employed, revealing 17 new sequences with structural similarity to LPMO, laccase, and peroxidase sequences and which are potentially new lignocellulose-degrading enzymes.

IMPORTANCE

An annotated reference genome has revealed
P. putredinis
NO1 as a useful resource for the identification of new lignocellulose-degrading enzymes for biorefining of woody plant biomass. Utilizing a “structure-omics”-based searching strategy, we identified new potentially lignocellulose-active sequences that would have been missed by traditional sequence searching methods. These new identifications, alongside the discovery of novel enzymatic functions from this underexplored lineage with the recent discovery of a new phenol oxidase that cleaves the main structural β-O-4 linkage in lignin from
P. putredinis
NO1, highlight the underexplored and poorly represented family Microascaceae as a particularly interesting candidate worthy of further exploration toward the valorization of high value biorenewable products.
The interaction of human immunodeficiency virus-1 and human endogenous retroviruses in patients (primary cell cultures) and cell line models
Authors: Mantovani Federica , Kitsou Konstantina , Paraskevis Dimitrios , Lagiou Pagona , Magiorkinis Gkikas
Published: October 2023

Human endogenous retroviruses (HERVs) integrated into the human genome millions of years ago, and their expression has been described both in healthy tissues and in pathology. In the present study, we study the differential expression of multiple HERV families in the presence of human immunodeficiency virus (HIV) infection in the peripheral blood mononuclear cells (PBMCs) of HIV-positive individuals, in HIV-infected cell lines, and
in vitro
HIV-infected macrophages/monocytes of healthy donors, utilizing publicly available data sets for secondary analysis using a pipeline appropriate for HERV transcription detection and comparison. We recognized significantly decreased expression of HERV-H in treatment-naïve HIV patients with viremia and increased expression of multiple HERV families in the PBMCs of HIV-infected individuals under combination antiretroviral therapy compared to healthy donors, in
in vitro
HIV-infected Stanford University pediatric T (SUP-T1) cells at 24 hours after HIV infection compared to non-infected SUP-T1 cells, and in
in vitro
HIV-infected MT4 T cells at 3 days after HIV infection compared to non-infected MT4 T cells. We recognized significantly increased expression of HERV-W, after HIV infection in monocyte-derived macrophage cell culture; no difference was found in HERV expression after HIV infection of monocyte cultures. We found a significantly decreased expression of HERV-K (HML-6) in donor-derived macrophage cultures at 36 hours after HIV infection, which does not persist at 6 days after infection. HIV infection modifies the expression of multiple HERV families in the PBMCs of HIV patients and in T cell-derived cultures, while the effect of HIV infection on HERV expression appears to be more restricted in cells of monocytic origin.

IMPORTANCE

In this work, we demonstrated that human immunodeficiency virus (HIV) infection leads to the modification of the human endogenous retrovirus (HERV) expression. Differential expression of multiple HERVs was found in peripheral blood mononuclear cells derived from HIV-infected patients compared to healthy donors and HIV-infected T cell cultures compared to non-infected. The effect of HIV presence on HERV expression appears to be more restricted in cells of monocytic origin, as only deregulation of HERV-W and HERV-K (HML-6) was found in these cell cultures after their infection with HIV. Multiple factors contribute to this aberrant HERV expression, and its levels appear to be modified in a time-dependent manner. Further studies and the development of optimized
in vitro
protocols are warranted to elucidate the interactions between HIV and HERVs in detail.
Wolbachia
interferes with Zika virus replication by hijacking cholesterol metabolism in mosquito cells
Authors: Edwards Brent , Ghedin Elodie , Voronin Denis
Published: October 2023

Zika virus is a member of the arbovirus
Flaviviridae
family transmitted by
Aedes
mosquitos and it is associated with microcephaly in infants born to infected mothers.
Wolbachia
is an intracellular gram-negative alpha-proteobacteria that infects many species of arthropods, including mosquitos. The presence of
Wolbachia
in mosquitos has been shown to control the vector population and suppress arbovirus transmission. One mechanism of
Wolbachia
-mediated interference with virus replication is competition over host resources between
Wolbachia
and the virus. We hypothesize that cholesterol metabolism is involved in
Wolbachia
-mediated virus suppression due to its important role in Zika virus replication. In this study, we determined that
Wolbachia
impacted virus replication by altering cholesterol biosynthesis in
Aedes albopictus
C6/36 cells, diverting resources from the host cell mevalonate (MVA) pathway to fulfill the needs of the bacteria. This resulted in a decrease of total cholesterol, increased
Wolbachia
loads, and decreased viral titers. Inhibition of the MVA pathway using fluvastatin decreased total cholesterol and viral titers, mimicking the effects of
Wolbachia
on the virus in
Wolbachia-
free cells. We also found that
Wolbachia-
infected cells had depleted lipid droplets, the main component of which is cholesterol esters. We confirmed that cholesterol esterases were upregulated in response to virus infection in C6/36 cells. Functional analysis showed that alteration of cholesterol metabolism simulated
Wolbachia
-mediated inhibition of virus infection in C6/36 cells. Our study provides a mechanism behind
Wolbachia
-induced interference of arbovirus replication and could help advance strategies to control arbovirus pathogens in insect vectors and human infections.

IMPORTANCE

Arthropod-borne viruses are emerging pathogens that are spread widely by mosquitos. Zika virus is an arbovirus that can infect humans and be transmitted from an infected mother to the fetus, potentially leading to microcephaly in infants. One promising strategy to prevent disease caused by arboviruses is to target the insect vector population. Recent field studies have shown that mosquito populations infected with
Wolbachia
bacteria suppress arbovirus replication and transmission. Here, we describe how intracellular bacteria redirect resources within their host cells and suppress Zika virus replication at the cellular level. Understanding the mechanism behind
Wolbachia
-induced interference of arbovirus replication could help advance strategies to control arbovirus pathogens in insect vectors and human populations.
Hundred-fold increase in SARS-CoV-2 spike antibody levels over three years in a hospital clinical laboratory
Authors: Caturegli Patrizio , Laeyendecker Oliver , Tobian Aaron A. R. , Sullivan David J.
Published: October 2023

Natural infection with the SARS-CoV-2 virus and vaccination increase the serum spike antibody levels. These levels, which differ among the various commercial assays, are used by the FDA to qualify individuals as potential COVID-19 convalescent plasma (CCP) donors. Over a 3-year period (April 2020–February 2023), we performed a retrospective analysis of spike IgG antibodies measured by a tertiary hospital clinical immunology laboratory using the Euroimmun SARS-CoV-2 IgG ELISA. The 3-year interval was classified into five periods based on the SARS-CoV-2 strain variant epidemiology. A total of 15,820 sera, derived from 11,022 individuals (6,362 females and 4,660 males) ranging from severe immunocompromised state to routine health visits, were tested. Spike IgG levels rose significantly over time, from a median ELISA 0.13 Arbitrary Units (AU) in the first period to 48.7 in the last period (
P
< 0.0001). The 80th percentile of the spike IgG distribution was 0.55, 8.1, 9.6, 64.9, and 151 AU in the five periods. Using 3.5 AU, the FDA threshold for qualifying CCP donors with this Euroimmun assay, the percentage of subjects eligible for CCP donation would have been 11%, 44%, 61%, 81%, and 91% in the five time periods. Overall, spike antibody levels have risen more than 100-fold during the pandemic, while SARS-CoV-2 variants have become resistant to monoclonal antibodies. Since CCP containing high titers of spike antibodies is known to be most effective against variants, restricting CCP donors to those with antibody values in the upper two deciles may allow greater therapeutic transfusion protection.

IMPORTANCE

Despite the evolution of SARS-CoV-2 variants of concern and ongoing transmission, COVID-19 hospitalization and mortality rates continue to decline. Both the percent seropositive and antibody levels have risen over the past 3 years. Here, we observe more than 90% seropositivity as well as more than a hundred-fold increase in spike IgG levels in a tertiary hospital clinical immunology laboratory setting. Antibody effector functions (such as neutralization, opsonization, and complement activation) and cell-mediated immunity all contribute to protection from COVID-19 progression to hospitalization, and all correlate to the total SARS-CoV-2 antibody levels. We recommend therapeutic COVID-19 convalescent plasma be restricted to the top 20% of potential donors to maintain activity against ongoing SARS-CoV-2 variant evolution.
Differential skin immune responses in mice intradermally infected with
Candida auris
and
Candida albicans
Authors: Datta Abhishek , Das Diprasom , Nett Jeniel E. , Vyas Jatin M. , Lionakis Michail S. , Thangamani Shankar
Published: October 2023

Candida auris
, an emerging multi-drug-resistant fungal pathogen, uniquely colonizes the human skin long term, leading to subsequent development of life-threatening invasive infections in humans. The factors regulating skin colonization of
C. auris
are not well understood. In this study, we established an intradermal mouse model of
C. auris
infection to define the innate and adaptive immune response to this emerging pathogen and compare it to
Candida albicans
. Our results indicate that compared to
C. albicans
-infected mice,
C. auris
-infected mouse skin tissue had significantly higher fungal load after 3 and 14 days post-infection.
C. auris
infection was associated with a significantly decreased accumulation of CD11b+ Ly6G+ neutrophils and increased numbers of CD11b+ Ly6 C
hi
inflammatory monocytes and CD11b+ CD207+ Langerhans cells at the site of infection. Furthermore, a significant decrease in the absolute numbers of type 3 innate lymphoid cells and Th17 cells was observed in
C. auris
-infected skin tissue. Taken together, our findings indicate that the skin immune responses are different between
C. auris
- and
C. albicans
-infected mice. The increased fungal load observed in
C. auris
-infected mouse skin tissue is associated with less potent innate and adaptive immune responses induced by this emerging pathogen relative to
C. albicans
.

IMPORTANCE

Candida auris
is a globally emerging fungal pathogen that transmits among individuals in hospitals and nursing home residents. Unlike other
Candida
species,
C. auris
predominantly colonizes and persists in skin tissue, resulting in outbreaks of nosocomial infections. Understanding the factors that regulate
C. auris
skin colonization is critical to develop novel preventive and therapeutic approaches against this emerging pathogen. We established a model of intradermal
C. auris
inoculation in mice and found that mice infected with
C. auris
elicit less potent innate and adaptive immune responses in the infected skin compared to
C. albicans
. These findings help explain the clinical observation of persistent
C. auris
colonization in skin tissue.
The
Alternaria alternata
StuA transcription factor interacting with the pH-responsive regulator PacC for the biosynthesis of host-selective toxin and virulence in citrus
Authors: Chen Yanan , Cao Yingzi , Jiao Chen , Sun Xuepeng , Gai Yunpeng , Zhu Zengrong , Li Hongye
Published: October 2023

The tangerine pathotype of
Alternaria alternata
produces a host-selective toxin termed
Alternaria citri
toxin (ACT). The molecular mechanisms underlying the global regulation and biosynthesis of ACT remain unknown. In the present study, the function of an APSES transcription factor StuA was investigated. StuA was shown to be required for ACT biosynthesis and fungal virulence. StuA was found, for the first time, to physically interact with a pH-responsive transcription regulator PacC using yeast two-hybrid, bimolecular fluorescence complementation, and GST pull-down assays. Functional analyses revealed that StuA and PacC regulate the expression of genes involved in toxin biosynthesis and virulence. Mutation of
stuA
via targeted gene deletion or silencing
pacC
yielded fungal strains that decreased the expression of seven toxin biosynthetic genes (
ACCT
) and toxin production. EMSA analyses revealed that PacC could bind to the promoters of
ACTT6
encoding an enoyl-CoA hydratase and
ACTTR
encoding an ACT pathway-specific transcription factor. Site-directed mutagenesis of five potential protein kinase A (PKA) phosphorylation sites in StuA revealed that none of the sites was involved in ACT production, indicating that the function of StuA in the regulation of
ACT
gene expression is not dependent on phosphorylation. Overall, our results confirmed that PacC is one of the key regulators interacting with StuA for the biosynthesis of ACT. Environmental pH may play a decisive role during
A. alternata
pathogenesis. Our results also revealed a previously unrecognized (StuA-PacC)→ACTTR module for the biosynthesis of ACT in
A. alternata
.

IMPORTANCE

In this study, we used
Alternaria alternata
as a biological model to report the role of StuA in phytopathogenic fungi. Our findings indicated that StuA is required for
Alternaria citri
toxin (ACT) biosynthesis and fungal virulence. In addition, StuA physically interacts with PacC. Disruption of
stuA
or
pacC
led to decreased expression of seven toxin biosynthetic genes (ACCT) and toxin production. PacC could recognize and bind to the promoter regions of
ACTT6
and
ACTTR
. Our results revealed a previously unrecognized (StuA-PacC)→ACTTR module for the biosynthesis of ACT in
A. alternata
, which also provides a framework for the study of StuA in other fungi.
Perceptions of key stakeholders on taxes on tobacco and alcohol products in Nepal
Authors: Acharya Yubraj , Karmacharya Vipassana , Paudel Uttam , Joshi Supriya , Ghimire Ramesh , Adhikari Shiva Raj
Published: October 2023

Background

Non-communicable diseases (NCDs) are on the rise in Nepal. Consumption of alcohol and tobacco products remains high. Taxes on these products are significantly below the rate recommended by the WHO. In an effort to understand the reasons behind the slow progress towards the adoption of higher health taxes to curb NCDs, we documented the perceptions of key stakeholders on health taxes, including perceived barriers and facilitators to adopting higher health taxes.

Methods

We conducted 45 in-depth interviews with individuals comprising government officials; producers, wholesale distributors and sellers of alcohol and tobacco products; and consumers and representatives from civil society organisations. We conducted a thematic analysis of the resulting data.

Results

Respondents from alcohol and tobacco industries are not supportive of higher health taxes. They argued that higher taxes can increase illicit trade and worsen inequality. Strikingly, several government officials shared the industries’ concerns, arguing that health taxes have limited potential to reduce consumption of alcohol and tobacco products to help curb NCDs. In terms of barriers to adoption of higher health taxes, several local government representatives opined that close ties between industries and politicians at the federal level is a major hindrance.

Conclusions

In order to adopt higher health taxes, the government will need to counter the false narrative pushed by alcohol and tobacco industries on the negative economic effects of such taxes. Health taxes earmarked for NCDs need to reflect the amount of revenue raised, reoriented towards prevention efforts and communicated clearly to the public.
Framing health taxes: a scoping review
Authors: Koon Adam D , Marten Robert
Published: October 2023

Health taxes are increasingly positioned as effective policy instruments for curbing non-communicable disease, improving health and raising government revenues. Their allure has caused many health advocates to look beyond tobacco and alcohol to other harmful products such as sugar-sweetened beverages (SSBs), salty foods, fatty foods and fossil fuels. These efforts, however, directly conflict with commercial actors’ interests. Both pro-tax health advocates and anti-tax industry representatives seek to frame health tax policy in favourable ways. Yet, little is known about which types of frames resonate in which settings, or how they deploy morals and values in their attempts to persuade. To fill this gap, we conducted a scoping review on framing health taxes using six databases in 2022. A total of 40 peer-reviewed empirical research articles, from 2006 to 2022, were identified from 20 different countries. Most research was conducted in high-income countries, published in the last 4 years and increasingly focused on excise taxes for SSBs. Studies captured multiple actors constructing context-specific frames, often tied to broader economic, health and administrative considerations. Actors also engaged in a range of political activities in addition to framing. We found some evidence that anti-tax framing strategies potentially incorporated a broader array of morals and social values. More in-country comparative research, particularly from low/middle-income countries, is needed to understand the politics of framing health taxes. We argue that these insights can improve efforts to advance health taxes by constraining corporate power, improving population level health and promoting greater social harmony.
Policy networks and competing interests in the development of the Mexican sugar-sweetened beverages tax
Authors: Carriedo Angela , Cairney Paul , Barquera Simón , Hawkins Benjamin
Published: October 2023

Introduction

Sugar taxes threaten the business models and profits of the food and beverage industry (F&BI), which has sought to avert, delay or influence the content of health taxes globally. Mexico introduced a sugar-sweetened beverage (SSB) tax in 2014 and other regulatory measures to improve population diets. This paper examines how policy networks emerged within and affected the development and implementation of the Mexican SSB tax.

Methods

This qualitative study analyses 31 interviews conducted with key stakeholders involved in the soda tax policy process and 145 documents, including grey literature and peer-reviewed literature. The policy network approach was used to map contacts, interconnections, relationships and links between the state, civil society and commercial actors involved in the SSB tax. These findings were used to examine the responsiveness, participation and accountability of the soda tax policy formulation.

Results

Complex interconnections were identified between state and non-state actors. These included advisory relationships, financial collaborations and personal connections between those in high-level positions. Relationships between the government and the F&BI were not always disclosed. International organisations and academics were identified as key financial or technical supporters of the tax. Key governance principles of participation, responsiveness and accountability were undermined by some of these relationships, including the participation of non-state actors in policy development and the powerful role of the F&BI in evaluation and monitoring.

Conclusion

This case study exemplifies the importance of links and networks between actors in health policymaking. The F&BI influence endangers the primary aim of the SSB tax to protect health. The identified links highlight the normalisation of connections among actors with competing aims and interests toward health, thereby jeopardising attempts to tackle obesity rates.
Making food-related health taxes palatable in sub-Saharan Africa: lessons from Ghana
Authors: Laar Amos , Amoah James M , Massawudu Labram M , Pereko Kingsley K A , Yeboah-Nkrumah Annabel , Amevinya Gideon S , Nanema Silver , Odame Emmanuel Ankrah , Agyekum Percy A , Mpereh Mary , Sandaare Sebastian
Published: October 2023

Amidst high burden of infectious diseases, undernutrition and micronutrient deficiencies, non-communicable diseases (NCDs) are predicted to become the leading cause of death in Ghana by 2030. NCDs are driven, to a large extent, by unhealthy food environments. Concerned, the Ghana Ministry of Health (MOH) has since 2012 sought to garner the support of all to address this challenge. We aimed to support the MOH to address the challenge through public health policy measures, but would soon be reminded that longstanding challenges to policy development such as data poverty, and policy inertia needed to be addressed. To do this, the we generated the needed evidence, curated the evidence, and availed the evidence to Ghanaian policymakers, researchers and civil society actors. Thus, we addressed the problem of data poverty using context-relevant research, and policy inertia through advocacy and scholar activism. In this paper, we share how a public interest coalition used context-relevant research, evidence-informed advocacy and scholar activism to valorise and increase demand for healthy food policy (including food-related health taxes) in Ghana.
Longstanding smoking associated with frontal brain lobe atrophy: a 32-year follow-up study in women
Authors: Johansson Lena , Guo Xinxin , Sacuiu Simona , Fässberg Madeleine Mellqvist , Kern Silke , Zettergren Anna , Skoog Ingmar
Published: October 2023

Objective

To examine the association between midlife tobacco smoking and late-life brain atrophy and white matter lesions.

Methods

The study includes 369 women from the Prospective Population Study of Women in Gothenburg, Sweden. Cigarette smoking was reported at baseline 1968 (mean age=44 years) and at follow-up in 1974–1975 and 1980–1981. CT of the brain was conducted 32 years after baseline examination (mean age=76 years) to evaluate cortical atrophy and white matter lesions. Multiple logistic regressions estimated associations between midlife smoking and late-life brain lesions. The final analyses were adjusted for alcohol consumption and several other covariates.

Results

Smoking in 1968–1969 (adjusted OR 1.85; 95% CI 1.12 to 3.04), in 1974–1975 (OR 2.37; 95% CI 1.39 to 4.04) and in 1980–1981 (OR 2.47; 95% CI 1.41 to 4.33) were associated with late-life frontal lobe atrophy (2000–2001). The strongest association was observed in women who reported smoking at all three midlife examinations (OR 2.63; 95% CI 1.44 to 4.78) and in those with more frequent alcohol consumption (OR 6.02; 95% CI 1.74 to 20.84). Smoking in 1980–1981 was also associated with late-life parietal lobe atrophy (OR 1.99; 95% CI 1.10 to 3.58). There were no associations between smoking and atrophy in the temporal or occipital lobe, or with white matter lesions.

Conclusion

Longstanding tobacco smoking was mainly associated with atrophy in the frontal lobe cortex. A long-term stimulation of nicotine receptors in the frontal neural pathway might be harmful for targeted brain cell.
Short-course radiotherapy combined with chemotherapy and PD-1 inhibitor in low-lying early rectal cancer: study protocol for a single-arm, multicentre, prospective, phase II trial (TORCH-E)
Authors: Chen Yajie , Wang Yaqi , Zhang Hui , Wan Juefeng , Shen Lijun , Wang Yan , Zhou Menglong , Wu Ruiyan , Yang Wang , Zhou Shujuan , Cai Sanjun , Li Xinxiang , Zhang Zhen , Xia Fan
Published: October 2023

Introduction

Current standard treatment for patients with early rectal cancer is radical surgical resection. Although radical surgery provides effective local tumour control, it also increases the mortality risk and considerable adverse effects, including bowel, bladder, sexual dysfunction and loss of anal function, especially in patients with low-lying rectal cancer. Recent studies have shown promising synergistic effects of the combination of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and radiotherapy in improving tumour regression. For patients who reach a clinical complete response (cCR) after neoadjuvant therapy, a ‘Watch & Wait’ (W&W) approach can be adopted to preserve anorectal function and improve quality of life. Thus, this study aims to explore the efficacy and safety of radiotherapy combined with chemotherapy and PD-1 antibody in patients with low early rectal cancer.

Methods and analysis

TORCH-E study is designed as a multicentre, prospective, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor in patients with cT1-3bN0M0 low rectal cancer. The trial was initiated in December 2022 and is currently recruiting patients, with an anticipated completion of participant enrolment by June of the following year. The enrolled 34 patients will receive SCRT (25 Gy/5 Fx), followed by four cycles of capecitabine plus oxaliplatin chemotherapy and PD-1 antibody (toripalimab) and finally receive surgery or the W&W strategy. The primary endpoint is the complete response (CR) rate, that is, the rate of pathological complete response (pCR) plus cCR. The secondary endpoints include organ preservation rate, 3-year local recurrence-free survival rate, 3-year disease-free survival rate, 3-year overall survival rate, grade 3–4 adverse effects rate and patients’ quality of life.

Ethics and dissemination

This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Center. Trial results will be disseminated via peer-reviewed journals and conference presentations.

Trial registration number

NCT05555888(ClinicalTrials.gov).
Effects of work-related electronic communication during non-working hours after work from home and office on fatigue, psychomotor vigilance performance and actigraphic sleep: observational study on information technology workers
Authors: Ikeda Hiroki , Kubo Tomohide , Nishimura Yuki , Izawa Shuhei
Published: October 2023

Objectives

This study examined the effects of work-related electronic communication (WREC) during non-working hours in the work from home or office setting on health.

Methods

The study recruited 98 information technology workers in a 9-day observational study. They recorded work–life events (eg, work style (working mostly from home or the office) and duration of WREC during non-working hours) and subjective ratings (eg, current fatigue, sleepiness and depression) and wore a sleep actigraph to measure objective sleep variables before bedtime every day. They completed the Brief Psychomotor Vigilance Test (PVT-B) before bedtime for 4 days.

Results

The frequency of WREC was significantly higher when working mostly from home than in the office (p<0.01). In addition, the duration of WREC was longer when working mostly from home than in the office (p<0.001). Linear or generalised linear mixed model analysis for fatigue, depression and PVT lapse revealed significant interaction effects between work style and WREC (all p<0.05). Post hoc analysis showed that the longer the WREC, the worse the fatigue and depression and the lower the lapse on working mostly from the office (all p<0.05).

Conclusions

Longer WREC is associated with worse fatigue and depression and lower lapse of PVT (higher alertness) before bedtime for working mostly from the office. Workers, especially those working from the office, should minimise WREC during non-working hours to maintain good health. Therefore, companies, managers and other relevant stakeholders should refrain from contacting workers during non-working hours.
Night work during pregnancy and small for gestational age: a Danish nationwide register-based cohort study
Authors: Begtrup Luise Moelenberg , Sejbaek Camilla Sandal , Flachs Esben Meulengracht , Garde Anne Helene , Specht Ina Olmer , Hansen Johnni , Kolstad Henrik A , Bonde Jens Peter Ellekilde , Hammer Paula Edeusa Cristina
Published: October 2023

Objective

The aim was to investigate the association between night work during pregnancy and risk of having a small for gestational age (SGA) child.

Methods

This cohort study had payroll data with detailed information on working hours for employees in all Danish administrative regions (primarily hospital employees) between 2007 and 2015, retrieved from the Danish Working Hour Database. Pregnancies, covariates and outcome were identified from the national birth registry. We used logistic regression to investigate the association between intensity and duration of night work during the first 32 pregnancy weeks and SGA. The adjusted model included age, body mass index, socioeconomic status and smoking. Using quantitative bias analysis and G-estimation, we explored potential healthy worker survivor bias (HWSB).

Results

The final cohort comprised 24 548 singleton pregnancies in 19 107 women, primarily nurses and medical doctors. None of the dimensions of night work were associated with an increased risk of SGA. We found a tendency towards higher risk of SGA in pregnancies where the women stopped having night shifts during pregnancy. Using G-estimation we found an OR<1 for the association between night work and SGA if all workers continued having night work during pregnancy compared with daywork only.

Conclusion

We found no increased risk of SGA in association with night work during pregnancy among healthcare workers. G-estimation was not precise enough to estimate the observed indication of HWSB. We need better data on pregnancy discomforts and complications to be able to safely rule out HWSB.
Master integrals for electroweak corrections to $$gg\rightarrow \gamma \gamma $$: light quark contributions
Authors: Fiore Gabriele , Williams Ciaran
Published: October 2023

We present a calculation of the master integrals (MI’s) required for the calculation of the Electroweak corrections to $$gg\rightarrow \gamma \gamma $$

g
g
→
γ
γ

production in which the process contains a light quark loop. The integrals can be broken down into five categories based on the flow of the heavy vector bosons throughout the loop. Three of the families are planar, and two are non-planar. We determine a canonical basis for each family which allows an efficient solution of the resulting differential equations via iterated integrals. We calculate the families in relevant physical kinematics and obtain an efficient numerical evaluation based on an implementation of Chen-iterated integrals.
Cooperation in bioluminescence: understanding the role of autoinducers by a stochastic random resistor model
Authors: Alfinito Eleonora , Beccaria Matteo , Cesaria Maura
Published: October 2023

Quorum sensing is a communication mechanism adopted by different bacterial strains for the regulation of gene transcription. It takes place through the exchange of molecules called autoinducers. Bioluminescence is an emergent threshold phenomenon shown by some bacteria strains. Its precise relationship to quorum sensing is a debated topic, particularly regarding the role of the different autoinducers used by bacteria. In this paper, assuming a direct relationship between bioluminescence and quorum sensing, we investigate the role of multiple autoinducers in the bioluminescence response of Vibrio harveyi, considered as a model bioluminescent strain, due to its quorum sensing circuitry involving an array of three different autoinducers. Experiments on mutants of this bacterium, obtained by suppression of one or more autoinducers, reveal their relative non-trivial relevance and cooperative interaction patterns. The proposed analysis is implemented on a regular lattice, whose nodes represent microbial entities equipped with charges, which represent the ability to up/down regulate the gene expression. Quorum sensing results from a Coulomb-type field, produced by the charges. In analogy with random resistor network models, the lattice is permeated by an effective current which accounts for the amount and distribution of the charges. We propose that the presence of different autoinducers correspond to a different up/down regulation of gene expression, i.e., to a different way to account for the charges. Then, by introducing a modulation of the charge dependence into the current flowing within the network, we show that it is able to describe the bioluminescence exhibited by V. harveyi mutants. Furthermore, modulation of the charge dependence allows the interactions between the different autoinducers to be taken into account, providing a prediction regarding the data obtainable under specific growth conditions.

Graphical abstract
Squeezing flow in the existence of carbon nanotubes past a Riga plate
Authors: Zari I. , Ali F. , Gul T. , Madubueze C. E. , Ali I.
Published: October 2023

Squeezing or squeeze flows have tremendous applications in applied fields, like engineering, biomedical sciences and rheological studies. This paper demonstrates the squeezing flow of kerosene-based nanoliquids between parallelly aligned plates, with a Riga-type fixed lower boundary. The effects of dispersing two types of copper-functionalized carbon nanotubes (CNTs), single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs) are examined. Using appropriate transformations, a self-similar ordinary differential system is derived from the governing model of partial differential equations and substantial boundary conditions. Using the homotopy analysis method (HAM) and the [Formula: see text] package, analytical and numerical estimates are obtained, respectively. For higher values of the squeezing parameter, dimensionless temperature increases, while velocity patterns are upside-down. Moreover, increments in dimensionless parameters representing Riga constituent width, modified Hartmann number, nanoparticle concentration and radiation parameter improve heat transfer rates and thermal boundary layer thickness, however, adversely affect velocity. Despite enhanced friction effects, numerical results show that the Nusselt number increases as nanoparticle loads and radiation parameters increase. This suggests that convection rates are improved over conduction rates. Excellent agreement is found between analytical and numerical evaluations. Apparently, it is noticed that MWCNTs perform better than SWCNTs.
Shear deformation modulates the electronic and optical properties of Al-doped arsenene
Authors: Qian Shaoran , Liu GuiLi , Gao Xuewen , Chen Yuling , Zhang Guoying
Published: October 2023

The influence of shear deformation on the electronic and optical properties of the Al-doped arsenene has been investigated using the first-nature principle based on density general function theory. Within this study, the 5.882% doping concentration in the Al-doped arsenene makes it reasonably stable and the doping of Al atoms causes the arsenene to exhibit quasi-metallic properties. The combined energy calculations show that the structural stability of the Al-doped arsenene is not significantly affected by shear deformation. With increased shear deformation, the band gap of intrinsic arsenene reduces, and the band gap of the Al-doped arsenene similarly does. Optical properties analysis indicates that shear deformation redshifts both the absorption and reflection peaks of the doped system.
Vehicle Trajectory Completion for Automatic Number Plate Recognition Data: A Temporal Knowledge Graph-Based Method
Authors: Long Zhe , Chen Jinjin , Zhang Zuping
Published: October 2023

Vehicle trajectories represent an essential information source in intelligent transportation systems. Prior trajectory completion models based on Automatic Number Plate Recognition (ANPR) data have typically depended on vehicle re-identification results or road network information or have employed static knowledge graphs to integrate the two information sources. However, these methods have not taken into account the implicit temporal characteristics of trajectories in ANPR data and have neglected individual vehicle preferences. To address this void, this study proposes a Temporal Knowledge Graph-based Vehicle Trajectory Completion Model (TKG-VTC). The model implementation comprises three stages: first, ANPR data are converted into a temporal trajectory knowledge graph; second, knowledge representation learning is conducted using nontemporal relations, a biased temporal regularizer and multivector embeddings to embed the knowledge on the graph; and finally, the embedded results are employed to perform link prediction for incomplete trajectories, thereby restoring vehicle trajectories in ANPR data. Through model evaluation metrics and dimensionality reduction experiments, TKG-VTC is observed to demonstrate the best performance in completing trajectories when compared to TComplEx, TNTComplEx, and TeLM. This research introduces an innovative application of employing temporal knowledge graphs for trajectory reconstruction, which eliminates dependence on vehicle re-identification and road network information in previous methodologies. This is advantageous for enhancing the performance and dependability of vehicle trajectory data in intelligent transportation systems, as well as facilitating the implementation of trajectory prediction, demand analysis, and accident warning applications.
Query Preference Analysis on Cascade Inference Human–Object Interaction Detection Transformer
Authors: Jia Weizhe , Ma Shiwei
Published: October 2023

Detection transformers (DETR) have provided a novel solution to human–object interaction detection in a set-prediction manner, thanks to expressive learnable queries. However, few studies covered how queries implicitly affect model behaviors, which might contain clues for model improvement. Therefore, we propose two dataset-based analysis tools: score state space and query preference map. They provide data on the distribution of model predictions, which can reveal overall-level and query-level model properties. Starting with our baseline model, we find the model naturally regresses object boxes to overlap human boxes in the edge case of no-object verbs (stand, etc.), even without a related loss. We encourage this by patching the supervision with virtual objects, resulting in more stable query preference. Moreover, we show that two-stage decoders designed for cascade inference do not decouple tasks as intended. We infer this is caused by the empty instances used as negative samples, which suggests a redesign in the matching scheme. Further, we reveal how adding an oracle-query-based teacher model affects query roles with a tiny gain, indicating room for refinement. Our findings demonstrate how a simple focus on query behaviors can provide insights for improving models.
Handwritten Odia Digit Recognition using Learning Systems: A Comparison of Neural Networks and Support Vector Machine Models
Authors: Sharma Urva , Bansal Rajat , Sarangi Pradeepta Kumar , Gupta Deepali , Rani Shalli , Khan Fazlullah , Srivastava Gautam
Published: October 2023

The Odia language is one of the many regional languages spoken in India. It is the official language of Odisha, a State in eastern India. The Odia language carries a 1500-year-old history and worldwide is spoken by more than 50 million people. The Odia digits are complex due to the presence of many curves in each character. Handwritten scripts are even more complex due to free-style writing. However, the development of an innovative machine learning model is essential because Odia scripts consist of a huge number of historical documents of more than 1000 years old. A robust automation method will help in converting historical documents into digital form and will help to preserve the documents. This will solve a big problem in society. This work experiments with handwritten Odia numerals by implementing two different classifiers. The first one is the implementation of a Convolutional Neural Network (CNN) and the second experiment implements a Support Vector Machine (SVM). Finally, results from both experiments have been compared. The dataset has been generated through software by writing the digits on MS Paint. Both CNN and SVM models have been implemented through Python programming to recognize the inputs into a particular class. Both training and testing of the models have been done using this dataset. The accuracy from the CNN Model is obtained to be 94.999% which is ≈95% and for SVM, the model accuracy is 86%. Comparing both results, it is concluded that the CNN model is comparatively better than the SVM classifier in the case of the proposed work.
Counter Measures to Combat Money Laundering in the New Digital Age
Authors: Subbagari Saikiran
Published: October 2023

Money Laundering has been a significant concern for governments, law enforcement agencies, and financial institutions worldwide. With the advancement of technology, money laundering techniques have evolved in the digital age, presenting new challenges for authorities and financial institutions. Criminals leverage innovative digital platforms, cryptocurrencies, and virtual assets to launder illicit funds while maintaining anonymity and complexity in their transactions. In this article, we examine the money laundering techniques in the digital age and the challenges posed by these techniques and the implications for the global financial system. Furthermore, the article explores the role of regulatory frameworks, technological solutions, and international cooperation in mitigating the risks associated with digital money laundering. We also explore the countermeasures implemented to detect and prevent these illicit activities. Enhanced Know Your Customer (KYC) regulations, robust transaction monitoring systems, international collaboration, and innovative technologies are among the critical measures to combat digital money laundering.
In-Depth Investigation of Manganese Dioxide as Pseudocapacitive Electrode in Lithium- and Sodium-Doped Ionic Liquids
Authors: Guillemin Thibaud , Douard Camille , Impellizzeri Anthony , Ewels Christopher P. , Humbert Bernard , Lethien Christophe , Donne Scott W. , Le Bideau Jean , Brousse Thierry
Published: October 2023

We investigate the contribution of pseudocapacitance to the overall capacitance of MnO2 electrodes in pure and alkaline-doped ionic liquids via two spectroscopic methods: step potential electrochemical spectroscopy (SPECS) and in situ Raman spectroscopy. For both characterization methods, thin-film electrodes of birnessite-like amorphous MnO2 were cycled in Ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, pure or doped with lithium or sodium. SPECS allows determination of the influence of the electrolyte composition on the electrochemical behavior of the MnO2 electrodes. Pseudocapacitive charge storage can account for over half of the total capacitance with alkaline-doped ionic liquids. In situ Raman spectroscopy provided insight into the reversible ion intercalation in the MnO2 structure, which appears to be controlled by EMIm+ cations. These findings are supported by density functional theory (DFT) calculations, which further help unveil the charge storage mechanism in birnessite-like amorphous MnO2 thin films operated in pure and alkaline-doped ionic liquids.