Background Breast cancer is the most common malignant tumor disease and the leading cause of female mortality. The evolution of nanomaterials science opens the opportunity to improve traditional cancer therapies, enhancing therapy efficiency and reducing side effects. Methods and major results Herein, protein cages conceived as enzymatic nanoreactors were designed and produced by using virus-like nanoparticles (VLPs) from Brome Mosaic Virus (BMV) and containing the catalytic activity of glucose oxidase enzyme (GOx). The GOx enzyme was encapsulated into the BMV capsid (VLP-GOx), and the resulting enzymatic nanoreactors were coated with human serum albumin (VLP-GOx@HSA) for breast tumor cell targeting. The effect of the synthesized GOx nanoreactors on breast tumor cell lines was studied in vitro. Both nanoreactor preparations VLP-GOx and VLP-GOx@HSA showed to be highly cytotoxic for breast tumor cell cultures. Cytotoxicity for human embryonic kidney cells was also found. The monitoring of nanoreactors treatement on triple negative breast cancer cells showed an evident production of oxygen by the catalase antioxidant enzyme induced by the high production of hydrogen peroxide from GOx activity. Conclusions and implications The nanoreactors containing GOx activity are fully suitable for cytotoxicity generation in tumor cells. The HSA functionalization of the VLP-GOx nanoreactors could result in a prevailing strategy to improve selective cancer targeting. The GOx containing enzymatic nanoreactors seems to be an interesting alternative to improve the current cancer therapy. In vivo studies are on going to reinforce the effectiveness of this treatment strategy.

Advances in sequencing technologies and declining costs are increasing the accessibility of large-scale biodiversity genomic datasets. To maximise the impact of these data, a careful, considered approach to data management is essential. However, challenges associated with the management of such datasets remain, exacerbated by uncertainty among the research community as to what constitutes best practices. As an interdisciplinary team with diverse data management experience, we recognise the growing need for guidance on comprehensive data management practices that minimise the risks of data loss, maximise efficiency for stand-alone projects, enhance opportunities for data reuse, facilitate Indigenous data sovereignty and uphold the FAIR and CARE Guiding Principles. Here, we describe four fictional personas reflecting user experiences with data management to identify data management challenges across the biodiversity genomics research ecosystem. We then use these personas to demonstrate realistic considerations, compromises, and actions for biodiversity genomic data management. We also launch the Biodiversity Genomics Data Management Hub (https://genomicsaotearoa.github.io/data-management-resources/), containing tips, tricks and resources to support biodiversity genomics researchers, especially those new to data management, in their journey towards best practice. The Hub also provides an opportunity for those biodiversity researchers whose expertise lies beyond genomics and are keen to advance their data management journey. We aim to support the biodiversity genomics community in embedding data management throughout the research lifecycle to maximise research impact and outcomes.

Introduction: A key reason for the failure of anti-tuberculosis (TB) treatment is missed doses (instances where medication is not taken). Adverse drug reactions (ADRs) are one cause of missed doses, but the global evidence for this, their relative contribution to missed doses versus other causes, the patterns of missed doses due to ADRs, and the specific ADRs associated with missed doses have not been appraised. We sought to address these questions through a scoping review. Methods: MEDLINE, Embase and Web of Science were searched on 3 November 2021 using terms around active TB, missed doses and treatment challenges. Studies reporting both ADR and missed dose data were examined. (PROSPERO: CRD42022295209). Results: Searches identified 108 eligible studies. 88/108 (81%) studies associated ADRs with an increase in missed doses. 33/61 (54%) studies documenting the reasons for missed doses gave ADRs as a primary reason. No studies examined patterns of missed doses due to ADRs. 41/108 (38%) studies examined associations between 68 types of ADR (across 15 organ systems) and missed doses. Nuance around ADR-missed doses relations regarding drug susceptibility testing profile and missed dose originator was found. Conclusions: There is extensive evidence that ADRs are a key driver for missed doses of anti-TB treatment. Some papers examined specific ADRs, none evaluated the patterns of missed doses due to ADRs, demonstrating a knowledge deficit. Knowing why doses both are and are not missed due to ADRs is essential in providing targeted interventions to improve treatment outcomes.

The interactions between different species in an ecosystem, such as predation and herbivory, are crucial for maintaining the ecosystem’s functioning, including pest control and nutrient cycling. Unfortunately, human activities are increasingly affecting these trophic relationships, contributing to the current decline in biodiversity, particularly due to urbanization and climate change. The intensity of trophic interactions is also affected by latitudinal gradients, which may be further impacted by urbanization, such as the urban island heat effect. This study aimed to investigate the hypothesis that the impact of human pressure on trophic interactions varies across different latitudes. To test this hypothesis, we selected 18 study sites at two latitudes (i.e., ~53°N and ~50°N) with varying human population density. We used artificial caterpillars placed on European beech branches to assess bird predation and took standardized pictures of the leaves to estimate insect herbivory. Remote sensing techniques were used to estimate human pressure. We found that the intensity of both bird predation and insect herbivory varied in response to human pressure, with opposite trends observed depending on the latitude. At the upper latitude, bird predation increased with human impact, while the opposite was observed at the lower latitude. All types of herbivory in both latitudes increased with urbanization. Moreover, at lower latitudes, species may face a disadvantage due to the urban heat island effect, as they tend to be relatively sensitive to temperature changes. Conversely, at higher latitudes, some species may benefit from a softer winter. Overall, this study highlights the complex and dynamic nature of trophic relationships in the face of human-driven changes to ecosystems. It also emphasizes the importance of considering both human pressure and latitudinal gradients when assessing the ecological consequences of future climate change scenarios, particularly in urban environments.

IL-17 has emerged as an important cytokine in protecting the host from mucosal infections, but also as a pathogenic determinant and therapeutic target in numerous autoimmune and inflammatory diseases (e.g. psoriasis, psoriatic arthritis and ankylosing spondylitis, inflammatory bowel disease and multiple sclerosis) [(1)](#ref-0001). The IL-17 family includes six members (IL-17A to IL-17F) that act through the IL-17 receptors [(1)](#ref-0001). The most studied IL-17A, as well as IL-17F, binds to IL-17RA and IL-17RC resulting in heterodimerization. Currently IL-17A, IL-17F, IL-17RA or IL-23, a cytokine produced by innate immune cells that promotes expansion of Th17 cell populations, are targetable by monoclonal antibodies (mAbs). These mAbs have been approved for the treatment of different autoimmune diseases, most notably psoriasis, where their efficacy has outperformed conventional non-steroidal anti-inflammatory and tumor necrosis factor (TNF) blocking drugs. However, clinical trials and real-life experience have shown an increase in fungal and bacterial upper respiratory tract infections in patients treated with mAbs that block IL-23/IL-17 signaling. Accordingly, single nucleotide polymorphisms in genes encoding IL-17A, IL-17RA, IL-17RC, IL-23, or NF-κB activator 1 (ACT1, an adapter protein downstream of the IL-17R) which abrogate cellular responsiveness to IL-17A, were associated with susceptibility to chronic mucocutaneous candidiasis (CMC), a persistent infection of the skin, nails, and/or mucous membranes with commensal Candida species [(2)](#ref-0002). So new effective targeted approaches in IL-17 signaling are desirable. Knizkova and colleagues identified a new adaptor molecule involved in the IL-17/IL-17R cascade [(3)](#ref-0003). Through murine and human cell models, the authors found that CMTM4 (CKLF Like MARVEL Transmembrane Domain Containing 4) constitutively bound to the subunit IL-17RC becoming integral part of the IL-17R signaling complex (IL-17RSC) upon IL-17A stimulation. CMTM4 promoted the surface expression of IL-17RC by regulating posttranslational modifications, especially IL-17RC glycosylation and trafficking to trans-Golgi up to plasma membrane. CMTM4 was required for the recruitment of adapter ACT1, for the activation of p38, JNK and transcription of genes encoding proinflammatory cytokines upon IL-17A stimulation (Figure 1A). Keratinocytes from the tail of Cmtm4−/− mice specifically express lower levels of IL-17RC respect to Cmtm4+/+ mice (Figure 1B). In vivo, when imiquimod (IMQ) was applied on the ears or shaven backs of Cmtm4−/− mice, they developed less severe psoriatic lesions and lower local expression of IL-17A target genes compared to Cmtm4+/+ mice (Figure 1C).

Multimodal studies evaluating associations between specific for Parkinson’s disease (PD) neuroimaging and neurophysiological biomarkers in revealing executive dysfunction mechanisms are scarce and needed to be validated. Hence, our study aimed to evaluate associations between electroencephalographic power spectral density (PSD-EEG), striatal [18F]Fluorodopa uptake and neuropsychological testing parameters in PD. Additional aim was to estimate PD diagnostic accuracy of the PSD-EEG parameters. We compared resting PSD-EEG, striatal [18F]Fluorodopa uptake ratio with positron emission computed tomography ([18F]FDOPA PET/CT), and neuropsychological test outcomes between PD patients and healthy controls, and then calculated correlations among these outcomes. Additionally we estimated PD diagnostic sensitivity and specificity (with the receiver operating characteristic curves) of the PSD-EEG parameters in reference to the gold diagnostic standard of the striatal [18F]FDOPA PET/CT uptake ratio.PD patients exhibited (i) increased power of the EEG theta and lower-alpha bands in the frontal lobe areas, (ii) decreased putaminal and caudate nuclei [18F]FDOPA PET/CT uptake ratios and (iii) longer performance times of part A and B of the Trail Making Test (TMT-A and TMT-B). Most of the PSD-EEG parameters negatively correlated with striatal [18F]FDOPA PET/CT uptake ratios and positively correlated with TMT-A and TMT-B. Furthermore, [18F]FDOPA PET/CT uptake ratios positively correlated with TMT-A and TMT-B. Theta and lower-alpha bands PSD-EEG were found to have high diagnostic accuracy. Our findings showed that slowing of EEG waves in the frontal lobe was correlated with striatal dopaminergic deficiency and executive dysfunction in mild PD patients, and appears to be a promising biomarker of PD-related executive dysfunction.

The higher elevation forests of Norfolk Island are regularly immersed in the clouds and scientific and anecdotal evidence suggests that in addition to rainfall, water is likely to be collected as cloud droplets are intercepted by the forest canopy. This water is likely to be important for the local hydrology and ecology, yet it has never been quantified. To address this, a field measurement campaign was established to measure hydrological inputs to the forest floor at two elevated forest sites in the Norfolk Island National Park. Instrumentation included throughfall and stemflow systems and measurements of rainfall in the open in nearby clearings. Sites exhibited very high stem density and basal area by international standards and delivery of water to the forest floor was dominated by stemflow because of the funnelling characteristics of the dominant palm and pine trees. Both sites showed similar hydrological behaviour with stemflow and throughfall of around 48% and 32%, respectively. Stemflow contributions of 48% far exceed observations from the literature which are typically less than 10%. Rainfall rarely occurred in the absence of low-level cloud and some cloud immersion events lasted for many days with hydrologic inputs continuing for extended periods despite rainfall not being observed in the open. Cloud interception accounted for approximately 20% of total water input at both sites which is equivalent to 25% extra water on top of rainfall measured in the open. From an island-wide perspective the calculated extra hydrological input is only small due to the limited spatial extent of elevated forest, however, the additional water is likely to be very important to local hydrological processes and the unique plants, insects and animals which inhabit the higher elevation forests of Norfolk Island.

Sexually transmitted infections (STIs) are a major global public health concern, with human papillomavirus (HPV) being one of the most common STIs affecting both men and women worldwide [1]. It is estimated that about 75% of sexually active people will contract HPV at some point in their lives [1]. The impact of HPV on health can be severe, causing various health problems such as genital warts, cervical, anal, penile, and oropharyngeal cancers [2].Several studies conducted in Africa have shown significant HPV prevalence rates among men who have sex with men (MSM). In sub-Saharan Africa, HPV was detected in a range of 19.1% to 100% of men, with a pooled prevalence of 78.2% among HIV-positive men and 49.4% among HIV-negative men [3]. Another study in South Africa found that HPV genotypes were detected in 72.8% of anal, 11.5% of oro-pharyngeal, and 15.3% of urine specimens of MSM, with multiple HPV types being more common in the anal canal [4]. Additionally, a study in Nigeria reported a higher prevalence of anal high-risk HPV (HR-HPV) among HIV-positive MSM compared to HIV-negative MSM [5], while another study in Mali found that a significant percentage of MSM had anal HPV infection of any genotypes, with a large portion being HR-HPV positive [6]. The increasing prevalence of anal HR-HPV among MSM in Africa highlights the urgent need for increased HPV screening and prevention measures targeted at this population, particularly HIV-positive MSM.HPV vaccination programs are highly effective in reducing the burden of HPV and associated diseases in both men and women [3]. The vaccine offers long-lasting protection against HPV infections that are most commonly associated with cancer [7]. Although the vaccine is primarily known for preventing cervical cancer in women, it can also prevent HPV-related cancers in men, such as anal, penile, and oropharyngeal cancers [7]. Moreover, vaccinating men can lead to herd immunity, which can protect women from HPV-related diseases [2]. Therefore, it is essential to prioritize the HPV vaccine for MSM who engage in anal sex to prevent HPV-related cancers and reduce the overall burden of HPV in Africa.However, the low uptake of the HPV vaccine in Africa, especially among high-risk individuals, is concerning despite the vaccine’s effectiveness in preventing HPV-related diseases. Only 14 of the 54 African nations have included the HPV vaccine in their national immunization programs for girls as of 2021, and no countries in western and central Africa have included widespread HPV vaccination in their national immunization programs [8 10]. Furthermore, currently, no countries in Africa offer HPV vaccination to men [8]. This means that individuals engaging in anal sex, who are at a higher risk of developing anal cancer, are not receiving the protection they need, despite the high prevalence of HPV infection among MSM. This underscores the urgent need to prioritize the inclusion of the HPV vaccine in national immunization programs in Africa, and to ensure equitable access to the vaccine for all persons, including MSM.To improve access to healthcare services and HPV vaccination for MSM in Africa, it is crucial to address both the structural and social barriers that hinder their access to these services. Some of the barriers that HPV-infected MSM face include a lack of information, general vaccine hesitancy, a lack of advice from healthcare professionals, expense and logistics, and the perception that HPV vaccination may encourage promiscuity [9]. Furthermore, discrimination and the criminalization of same-sex behavior can further prevent MSM from accessing healthcare programs [10].A comprehensive approach is necessary to overcome these barriers and improve access to healthcare services and HPV vaccination for MSM in Africa. This includes community-based interventions [11], and healthcare professional training to increase awareness about HPV, the benefits of vaccination, and to reduce vaccine hesitancy among MSM [12]. Healthcare professionals should also receive training to provide culturally competent care to meet the unique healthcare needs of MSM in a non-judgmental manner [12]. Policy changes are also necessary to eliminate discrimination and criminalization of same-sex behavior and enable MSM to access healthcare services without fear of stigma or persecution [10]. Moreover, to increase vaccine coverage in Africa, the HPV vaccine should be made affordable and accessible to all individuals, regardless of their socioeconomic status [10]. This can be achieved by implementing community-based vaccination programs, mobile clinics, and school-based vaccination programs. Overall, these interventions can help to improve vaccination rates and increase access to healthcare services for MSM in Africa, ultimately leading to better health outcomes and reducing health disparities.

A document by Tejash Shahi. Click on the document to view its contents.

A Series of Unfortunate Events: Long-neglected Malpositioned Pacemaker and its ConsequencesAbdelrahman Osman, BS and Ali Ahmad, MD.

IntroductionPulmonary alveolar microlithiasis (PAM) is an uncommon, autosomal recessive lung disease with high penetrance (OMIM #265 100) and is considered to be a monogenic disorder. 1 The only known pathogenic gene is solute carrier family 34 member 2 (SLC34A2) (Entrez Gene ID 10568).2-4 SLC34A2 mutations lead to the accumulation of calcium phosphate in the alveoli, restrict alveolar dilatation, and then progress to a restrictive lung function complicated with reduced dynamic and static volumes.5, 6 Dyspnea is the most frequent symptom, followed by dry cough, chest pain, asthenia, pneumothorax, pulmonary fibrosis, and cor pulmonale.7-10While children are always in the onset at the early stage of PAM and usually remain asymptomatic when diagnosed; however, some can present with dry cough, exertional dyspnea, and chronic hypoxic signs, including clubbing.3 Recently, some complications with PAM have been reported, such as asthma, pneumomediastinum, subcutaneous emphysema, and so on.11-14PAM is difficult to be diagnosed because of nonspecific symptoms in children. The diagnosis of PAM is often based on radiographic studies at first, and an exact diagnosis requires at least one additional clinical feature including genetic testing demonstrating a mutation in SLC34A2, microlith analysis, or histopathology.15 Gradually, it has been a tendency that gene analysis would play an increasingly important role in the diagnostic procedure. Bendstrup et al. summarized 30 genetic variants of SLC34A2 in 2020.16In this case, we identified a PAM patient complicated with bronchitis obliterans by computerized tomography (CT), bronchoscopy and whole-exome-sequencing. Two novel compound heterozygous gene mutations, gain (EXON:2-6 duplication) and c.1218C>A (p. Phe406Leu) were identified to expand the spectrum of gene mutations.

First Reported Rhodotorula mucilaginosa Brain Abscess: Found As Coinfection in Woman with Common Variable Immune DeficiencyAuthors: Arjun Bhatt, B.A.1Melinda S. Dunlap, M.D.2Han Pham, M.D.3Kimmo J. Hatanpaa, M.D., Ph.D3Philip Boyer, M.D., Ph.D3Rita M. Gander, Ph.D3Anna G. Symmes, M.D.1Affiliations: Department of Internal Medicine1Brody School of MedicineGreenville, North CarolinaDepartments of Internal Medicine2 and Pathology3University of Texas Southwestern Medical CenterDallas, Texas

Cameroon was among the most affected African countries during the first wave of the COVID-19 pandemic; however, the true prevalence of SARS-CoV-2 remains unknown. From October-December 2020 we conducted a cross-sectional, age-stratified SARS-CoV-2 seroepidemiological survey at 30 purposively selected community-based sites across Cameroon’s 10 regional capitals, sampling 10,000 individuals aged 5 years or older. We employed a parallel SARS-CoV-2 antibody testing algorithm (WANTAI ELISA and Abbot Architect) to improve both the positive predictive value and negative predictive value of seroprevalence. The overall weighted and adjusted seroprevalence of SARS-CoV-2 antibodies across the 10 urban capitals of Cameroon was 10.5% (95% CI: 9.1%-12.0%) among participants aged ≥5 years. Of the 9332 participants, 730 males (13.1%, 95% CI: 11.5%-14.9%) had SARS-CoV-2 antibodies compared to 293 females (8.0%, 95% CI: 6.8%—9.3%). Among those who reported a comorbidity at the time of testing, 15.8% (95% CI: 12.8%-19.4%) were seropositive. We estimated that over 2 million SARS-CoV-2 infections occurred in the 10 regional capitals of Cameroon between October and December 2020, compared to 21,160 cases officially reported at that time translating to one laboratory-confirmed case was reported for every 110 SARS-CoV-2 infections across the 10 urban capitals. This study’s findings point to extensive and under-reported circulation of SARS-CoV-2 in Cameroon– an almost 100-fold more cases compared to the number of cases reported to the World Health Organization. This finding highlights the importance of conducting serosurveys, especially in settings where access to testing may be limited and to repeat such surveys as part of pandemic tracking.

A document by Marhaba Iqbal. Click on the document to view its contents.

Monitoring is a prerequisite for evidence-based wildlife management, yet conventional monitoring approaches are often ineffective for species occurring at low densities. However, some species such as large mammals are often observed by lay people and this information can be leveraged through citizen science monitoring schemes. Assessing the quantity, quality, and potential biases of such data sources is crucial before making inferences at scale. For Eurasian moose (Alces alces), a species currently reoccurring in north-eastern Germany in low numbers, we compared three different citizen science tools: a mail/email report system, a smartphone application, and a webpage. Among these monitoring tools, the mail/email report system yielded the greatest number of moose reports in absolute and in standardized (corrected for time effort) terms. The reported moose were predominantly identified as single, adult, male individuals, and reports occurred mostly during late summer. Overlaying citizen science data with independently generated habitat suitability and connectivity maps showed that members of the public detected moose in suitable habitats but not necessarily in movement corridors. Also, moose detections were often recorded near roads, suggestive of spatial bias in sampling effort. Our results suggest that citizen science-based data collection can be facilitated by brief, intuitive digital reporting systems. However, inference from the resulting data can be limited due to unquantified and possibly biased sampling effort. To overcome these challenges, we offer specific recommendations such as engaging outdoor enthusiasts in suitable moose habitats, for improving quantity, quality and analysis of citizen science-based data for making robust inferences about wildlife populations.

1. Grassy ecosystems cover ~40% of the global land surface and are an integral component of the global carbon cycle. Grass litter decomposes via a combination of ultraviolet radiation degradation (which returns carbon to the atmosphere rapidly) and biological decomposition (a slower carbon pathway). As such, decomposition and carbon storage in grasslands may vary with climate and exposure to solar radiation. We investigated rates of grass litter decomposition in Australian temperate grasslands along a climate gradient to uncouple the relative importance of UV radiation and climate on decomposition. 2. Litterbags containing two common native grass species were deployed at six grassland sites across a precipitation gradient (380-890 mm) in south-eastern Australia. Bags were retrieved over 39 weeks to measure mass loss from decomposition. We used shade treatments to partition UV degradation from biological decomposition. 3. The shade treatment consistently reduced the rate of decomposition relative to full-sun treatments at all sites; there was no significant difference in the effect size of the shade treatment among sites. The rate of decomposition was positively correlated with rainfall midway through the experiment, but there were no significant differences in total decomposition among sites after 39 weeks. In general, the shape of decomposition curves was more linear than has typically been observed in global decomposition studies. 4. Synthesis: We found that UV exposure was a strong contributor to litter decomposition in temperate Australian grasslands. This effect was not influenced by climatic variables and may be related to a period of photopriming prior to further biotic decomposition. This study highlights the importance of litter composition and UV exposure in our understanding of how decomposition patterns contribute to global carbon cycling.

Effective treatment, but also proper diagnosis of cardiovascular diseases, remains a major challenge in everyday practice. A quick, safe, and economically acceptable non-invasive procedure should play a leading role in cardiovascular risk assessment before invasive diagnostics is performed. The staging of subclinical atherosclerosis may help in further clinical decisions. Safe, widely available, and relatively inexpensive, ultrasonography is a promising examination that should find wider application in clinical practice. The latest ESC guidelines emphasize the usefulness of carotid ultrasound in the diagnosis of coronary artery disease (CAD) and subclinical assessment of atherosclerosis, which help to determine the level of cardiovascular risk. Ultrasound examination of peripheral arteries, especially superficial vessels such as the femoral arteries, is quite easy, quick, and accurate. Other vascular beds, such as iliac and renal, are more demanding to examine, but can also provide valuable information. This review summarizes important studies comparing the severity of atherosclerosis in ultrasound-visible vascular beds in patients with established CAD. We especially emphasize the benefits of the combined assessment of atherosclerosis features, which were characterized by high sensitivity and specificity in the diagnosis of CAD and other serious cardiovascular diseases.

This paper fuses ideas from Reinforcement Learning (RL), Learning from Demonstration (LfD), and Ensemble Learning into a single paradigm. Knowledge from a mixture of control algorithms (experts) are used to constrain the action space of the agent, enabling faster RL refining of a control policy, by avoiding unnecessary explorative actions. Domain-specific knowledge of each expert is exploited. However, the resulting policy is robust against errors of individual experts, since it is refined by a RL reward function without copying any particular demonstration. Our method has the potential to supplement existing RLfD methods when multiple algorithmic approaches are available to function as experts. We illustrate our method in the context of a Visual Servoing (VS) task, in which a 7-dof robot arm is controlled to maintain a desired pose relative to a target object. We explore four methods for bounding the actions of the RL agent during training. These methods include using a hypercube and convex hull with modified loss functions, ignoring actions outside the convex hull, and projecting actions onto the convex hull. We compare the training progress of each method with and without using the expert demonstrators. Our experiments show that using the convex hull with a modified loss function significantly improves training progress. Furthermore, we demonstrate faster VS error convergence while maintaining higher manipulability of the arm, compared to classical image-based VS, position-based VS, and hybrid-decoupled VS.