Pancreatic β-cell-specific clock knock-out mice develop β cell oxidative-stress and failure, as well as glucose-intolerance. How inflammatory stress affects the cellular clock is under-investigated. Real-time recording of Per2:luciferase reporter activity in murine and human pancreatic islets demonstrated that the proinflammatory cytokine Interleukin-1β (IL-1β) lengthened the circadian period. qPCR-profiling of core clock gene expression in insulin-producing cells suggested that the combination of the proinflammatory cytokines IL-1β and Interferon-γ (IFN-γ) caused pronounced but uncoordinated increases in mRNA levels of multiple core clock genes, in particular of Reverse-erythroblastosis virus α (Rev-erbα), in a dose- and time-dependent manner. The REV-ERBα/β agonist SR9009, used to mimic cytokine-mediated Rev-erbα induction, reduced constitutive and cytokine-induced Brain and muscle arnt-like 1 (Bmal1) mRNA levels in INS-1 cells as expected. SR9009 induced reactive oxygen species (ROS), reduced insulin-1/2 (Ins-1/2) mRNA and accumulated- and glucose-stimulated insulin secretion, reduced cell-viability, and increased apoptosis levels, reminiscent of cytokine toxicity. In contrast low (<5,0 μM) concentrations of SR9009 increased Ins-1 mRNA and accumulated insulin-secretion without affecting INS-1 cell viability, mirroring low-concentration IL-1β mediated β-cell stimulation. Inhibiting nitric oxide (NO) synthesis, the lysine deacetylase HDAC3 and the immunoproteasome reduced cytokine-mediated increases in clock gene expression. In conclusion, the cytokine-combination perturbed the intrinsic clocks operative in mouse and human pancreatic islets and induced uncoordinated clock gene expression in INS-1 cells, the latter effect associated with NO, HDAC3 and immunoproteasome activity.

This article presents an overview of the first AI-human collaborated album, Hello World, by SKYGGE, which utilizes Sony’s Flow Machines technologies. This case study is situated within an overview of current and emerging uses of AI in popular music production, and connects those uses with myths and fears that have circulated in discourses concerning the use of AI in general, but also in music specifically. By proposing the concept of an audio uncanny valley in relation to AIPM (artificial intelligence popular music), this article offers a lens through which to examine the more novel and unusual melodies and harmonisations made possible through AI music generation, and questions how this content relates to wider speculations about posthumanism, sincerity, and authenticity in both popular music, and more wider assumptions of anthropocentric creativity. In its documentation of the emergence of a new era of popular music, the AI era, this article surveys: (1) the current landscape of artificial intelligence popular music focusing on the use of Markov models for generative purposes; (2) posthumanist creativity and the potential for an audio uncanny valley; and (3) issues of perceived authenticity in the technologically mediated “voice”.

Background/Objectives: The aim of the narrative review was to identify information on the impact of technological interventions (such as telehealth and mobile health) on the health promotion of cardiac patients from diverse populations; Methods: Online databases of PubMed, and Cochrane Library were searched for articles in the English language regarding technological interventions for health promotion in cardiac patients. In addition, a methodological quality control process was conducted. Exclusion was based on first reading the abstract and then the full manuscript confirming content was not related to cardiac patients and technological interventions; Results: 11 studies were included in the review after quality control analysis. The sample size reported in these studies ranged from 12 to 1424 subjects. In 8 studies mobile phones, smartphones and apps were used as mHealth intervention with tracking and texting component; 2 studies used videoconferencing as a digital intervention program, while one study focused on using physical activity trackers; Conclusions: This review highlights the digital divide as individuals with limited eHealth literacy and lack of technological knowledge are not motivated or able participate in these interventions. Finding methods to overcome these barriers are important and can be solved to some extent by providing the technology and technical support.

Crosstalk between the BMP and TGF-β signaling pathways regulates many complex developmental processes from the earliest stages of embryogenesis throughout adult life. In many situations, the two signaling pathways act reciprocally. For example, TGF-β signaling is generally pro-fibrotic whereas BMP signaling is anti-fibrotic and pro-calcific. Sex-specific differences occur in many diseases including cardiovascular pathologies. Differing ratios of fibrosis and calcification in stenotic valves suggests that BMP/TGF-β signaling may vary in men and women. In this review, we focus on the current understanding of the interplay between sex and BMP/TGF-β signaling and pose several unanswered questions.

Clustering coefficient measures are key complex network analysis tools. We examine local and global clustering coefficient measures with respect to the lexicographic graph product. As a preliminary condition, we analyze the $K_3$ subgraph structure focused on vertex inclusion with respect to the product graph. From this structure, we determine both the clustering coefficient for the product graph vertices and the average clustering coefficient for the product graph.

Osteomyelitis is a significant cause of total carcass condemnation in pigs at the slaughterhouse. The decision for total condemnation of a pig carcass for osteomyelitis is often based on traditional perceptions of the risk of pyemia, leading to controversy among Official Veterinarians (OV) in the industry. This review aims to provide a more comprehensive understanding of the etiopatho-genesis of osteomyelitis in pigs, the microorganisms involved, and the risk factors. It also high-lights the urgent need for a more uniform method to evaluate osteomyelitis cases, which could significantly reduce economic losses in the industry. Lesions originating from tail-biting, tail docking, castration, teeth resection, and raw management are described as risk factors for oste-omyelitis. Osteomyelitis is caused by the entry of pathogens into the bloodstream of the animal through an open wound. The most described pathogens are Trueperella monocytogenes, Staphylo-coccus aureus, and Streptococcus spp. At slaughter, OVs condemn carcasses with osteomyelitis due to pyemia. Signs of acute disease are essential to identify pyemia cases. In chronic cases, total carcass condemnation can be avoided depending on the number of lesions and number of vertebrae af-fected. A clear overall image of the problem would help authorities in various countries adopt a more homogenous approach.

Although Lov\'{a}sz introduced the graph exponential $G^K$ in 1967, this product has received little attention. This paper focuses on the number of components in $G^K$ when exponent $K$ is a complete graph $K_n$. For a connected bipartite $G$, when $K$ is $K_2$, $G^{K_2}$ has three components; and when $K$ is $K_n$ with $n>2$, $G^{K_n}$ produces $\lceil\frac{n+1}{2}\rceil$ components. A connected $G$ with an odd cycle produces one component in $G^{K_n}$.

Introduced in 1967 by Lov\'{a}sz, graph exponentiation has received little attention over the past several decades. Since graph exponentiation produces large graphs and any graph can be constructed utilizing its adjacency matrix, we provide a four step linear construction algorithm that generates the adjacency matrix for the graph exponential.

This paper examines the most prominent “progressive” American religious groups’ (as defined by those that liberalized early on the issue of birth control, circa 1930) views of women between the first and second waves of the feminist movement (1930-1965). We find that some groups have indeed had a long and outspoken support for women’s equality. Using their modern-day names, these groups, the United Church of Christ, the Unitarian Universalist Church, and to a lesser extent, the Society of Friends, or Quakers, professed strong support for women’s issues, early, and often. However, we also find that prominent progressive groups –the Protestant Episcopal Church, the Methodist Episcopal Church and the United Presbyterian Church, were virtually silent on the issue of women’s rights – even as the second wave of the feminist movement was picking up steam – as late as 1965.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

A checklist of parasitic cymothoids from Malaysian waters is presented based on available literature and material collected from 2010 to 2020. Most of the collected specimens were recorded from waters of Terengganu, east coast of Peninsular Malaysia (facing South China Sea), whereas literature records were represented from Sarawak, along the Miri coast of northwest Borneo. The checklist comprises 18 species under 10 genera, seven of which are new records from Malaysia, which includes Anilocra nemipteri Bruce, 1987; Ceratothoa barracuda Martin, Bruce and Nowak, 2015; Ceratothoa carinata (Bianconi, 1869); Cymothoa epimerica Avdeev, 1979; Elthusa sigani Bruce, 1990; Joryma engraulidis (Barnard, 1936) and Renocila richardsonae Williams and Bunkley-Williams, 1992. Eight new host records are based on collected specimens: Anilocra nemipteri was dorsally attached on Nemipterus nemurus (Bleeker 1857), Nemipterus nematophorus (Bleeker 1854), Nemipterus tambuloides (Bleeker 1853), and Nemipterus thosaporni Russell 1991 (family Nemipteridae); Ceratothoa carinata was found in the buccal cavity of Decapterus macrosoma Bleeker 1851 (family Carangidae); Cymothoa eremita (Brunnich, 1783) was attached in the buccal cavity of Nemipterus tambuloides and Nemipterus furcosus (Valenciennes 1830); Elthusa sigani was found attached on Pterois russelli Bennett 1831 (family Scorpaenidae); and Renocila richardsonae was attached on the caudal fin of Upeneus japonicus (Houttuyn 1782) (family Mullidae). All cymothoid species listed here are known to have a Central Indo Pacific distribution, with some ranging as far as the western Indian Ocean. The cymothoid-host association is here listed from 28 fish families, with the most common reported from Carangidae (pompanos, jack mackerels, runners, scads), Engraulidae (anchovies) and Leiognathidae (ponyfishes, slipmouths). This paper is the first comprehensive treatment to update both verified literature data and deposited specimens, with a key for the family Cymothoidae in Malaysian waters.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

Although the vegetative stage of indoor cannabis production can be relatively short in duration, there is a high energy demand due to higher light intensities (LI) than the clonal propagation stage and longer photoperiods than the flowering stage (i.e., 16 – 24 hours vs. 12 hours). While electric lighting is a major component of both energy consumption and overall production costs, there is a lack of scientific information to guide cultivators in selecting a LI that corresponds to their vegetative stage production strategies. To determine the vegetative plant responses to LI, clonal plants of ‘Gelato’ were grown for 21 days with canopy-level photosynthetic photon flux densities (PPFD) ranging between 135 and 1430 µmol·m^-2·s^-1 on a 16-hour photoperiod (i.e., daily light integrals of ≈ 8 to 80 mol·m^-2·d^-1). Plant height and growth index responded quadratically; the number of nodes, stem thickness, and aboveground dry weight increased asymptotically; and internode length and water content of aboveground tissues decreased linearly with increasing LI. Foliar attributes had varying responses to LI. Chlorophyll content index increased asymptotically, leaf size decreased linearly and specific leaf weight increased linearly with increasing LI. Generally, PPFD levels of ≈ 900 µmol·m^-2·s^-1 produced compact, robust plants that are commercially relevant, while PPFD levels of ≈ 600 µmol·m^-2·s^-1 promoted plant morphology with more open architecture – to increase airflow and reduce the potential foliar pests in compact (i.e., indica-dominant) genotypes.

Most commercial Cannabis sativa L. (cannabis) genotypes are short-day plants and cultivators typically use a 12.0 h uninterrupted dark period to induce flowering; however, scientific information is lacking to prove this is the optimal dark period for all genotypes, and cultivar specific photoperiods may increase productivity. Tissue culture can be used for research requiring multiple treatments, proper replication, and in a controlled environment on a smaller scale compared to greenhouse and indoor facilities. To determine whether cannabis explants can flower under varied photoperiods in vitro, explants were grown under one of six photoperiod treatments: 12.0, 13.2, 13.8, 14.4, 15.0, and 16.0 h for four weeks. The percentage of flowering explants was highest under 12.0 and 13.2 h treatments. There were no treatment effects on the fresh weight, final height, or growth index of the explants. The results suggest an uninterrupted dark period of at least 10.8 h (i.e. 13.2 h photoperiod) is needed to induce the flowering of this genotype. In vitro flowering could provide a unique and high throughput approach to study floral/seed development and secondary metabolism in cannabis under highly controlled conditions. Further research should determine if this response is the same on a whole plant level.

Current instrumental technology in evaluating performance of skin care creams is still rather limited and there are no industrial standard testing equipment, method and performance specifications for it. In this paper, we report our attempt in using an instrument called PhabrOmeter for this purpose. PhabrOmeter is a commercialized instrument for sensory performance evaluation of textiles, leather, paper and nonwoven and has been designated by American Association of Textile Chemists and Colorists (AATCC) as a standard test method for textiles, AATCC TM 202 in 2013. By adopting artificial skin samples treated with skin care creams, we have developed a procedure to apply this instrument for evaluation of skin care creams from sample preparation, measurement to data analysis and interpretation. The results using commercial skin care creams to demonstrate the feasibility and advantages of this instrument are provided.

The mechanisms of treatment-resistant epilepsy remain unclear. We have previously shown that frontline administration of therapeutic doses of lamotrigine (LTG), which preferentially inhibits the fast-inactivation state of sodium channels, during corneal kindling of mice promotes cross-resistance to several other antiseizure medicines (ASMs). However, whether this phenomenon extends to monotherapy with ASMs that stabilize the slow inactivation state of sodium channels is unknown. Therefore, this study assessed whether lacosamide (LCM) monotherapy during corneal kindling would promote future development of drug-resistant focal seizures in mice. Male CF-1 mice (n=40/group; 18-25 g) were administered an anticonvulsant dose of LCM (4.5 mg/kg, ip), LTG (8.5 mg/kg, ip), or vehicle (0.5% methylcellulose) twice daily for two weeks during kindling. A subset of mice (n=10/group) were euthanized 1 day after kindling for immunohistochemical assessment of astrogliosis, neurogenesis, and neuropathology. The dose-related antiseizure efficacy of distinct ASMs, LTG, LCM, carbamazepine, levetiracetam, gabapentin, perampanel, valproic acid, phenobarbital, and topiramate was then assessed in remaining kindled mice. Neither LCM nor LTG administration prevented kindling: 29/39 vehicle-exposed mice were kindled; 33/40 LTG-exposed mice were kindled; and 31/40 LCM-exposed mice were kindled. Mice administered LCM or LTG during kindling became resistant to escalating doses of LCM, LTG, and carbamazepine. Perampanel, valproic acid, and phenobarbital were less potent in LTG- and LCM-kindled mice, whereas levetiracetam and gabapentin retained equivalent potency across groups. Notable differences in reactive gliosis and neurogenesis were also appreciated. This study indicates that early, repeated administration of sodium channel blocking ASMs, regardless of inactivation state preference, promotes pharmacoresistant chronic seizures. Inappropriate ASM monotherapy in newly diagnosed epilepsy may thus be one driver of future drug-resistance, with resistance being highly ASM class-specific.

Higher consumption of fruit and vegetables has been associated with a lower risk of various chronic diseases including coronary heart disease, obesity, and certain cancers. Recently, fruit and vegetable intake has also been linked with mental health, including depression. This systematic review aimed to evaluate the association between fruit and vegetable intake and depressive symptoms in young people and adults aged 15-45. The systematic review focused on peer-reviewed cohort studies published from 1 January 2000 to 31 August 2020 using searches of six electronic databases. The exposure was fruit and vegetable consumption analysed both separately and/or together, and the outcome was depression or depressive symptoms. Data from eligible studies were extracted according to predefined criteria and the studies were appraised using the Newcastle-Ottawa Scale (NOS) for Cohort Studies to evaluate for study quality and risk of bias. To evaluate the association between fruit and vegetable consumption and depressive symptoms, a narrative synthesis was conducted. Of 9667 potentially relevant studies that were screened for title and abstracts, 144 full text studies were evaluated, and 12 studies from seven countries were deemed eligible and included in the qualitative synthesis. Using the NOS framework one study was categorised as ‘very good’ quality, ten studies were ‘good’ quality, and two studies were ‘moderate’ quality. With respect to combined fruit and vegetable consumption, two studies demonstrated an inverse association with depression. When the effects of fruit and vegetable on depression were analysed separately, five studies showed significant associations in fruit consumption, and two studies showed significant associations in vegetable consumption. Four studies showed no association between combined fruit and vegetable consumption and depression, one study showed no association between fruit consumption and depression, and two studies showed no association between vegetable consumption and depression. Despite some contradictory results in the studies included in this review, the evidence seems to be building that a possible association exists, and this may have implications for addressing the burden of mental illness in young people and adults aged 15-45 years. Well-designed prospective cohort studies are needed to provide more robust evidence on the diet-depression relationship.

Industrial hemp (Cannabis sativa L.) is an attractive candidate for sustainable pest management due to its abundance of bioactive compounds with potential pesticidal properties. Solvent choice has a significant impact on the extraction efficiency of bioactive compounds. Deep Eutectic Solvents (DESs) are gaining popularity in extraction because they are safe and environmentally friendly, making them viable alternatives to organic solvents (OSs). This research first compared the extraction efficiency of OSs on the extraction of phytochemicals from the infloresences of two hemp varieties, Citrus and Cherry Dwarf. Inflorescences were extracted using three OSs, ethanol, ethyl acetate, and hexane. The highest level of cannabidiol (CBD; 0.69%) was extracted from Cherry Dwarf using ethanol while the level of delta-9 tetrahydrocannabinol THC (0.19%) was essentially the same in both. Therefore, Cherry Dwarf was selected to compare the extraction efficiency of DESs to the OSs. The DESs were choline chloride/ethylene glycol, citric acid/ethylene glycol, menthol/lauric acid, choline chloride/urea and choline chloride/glycerol. In the targeted analysis, choline chloride/ethylene glycol extracted the highest amount of CBD (0.87%) followed by choline chloride/urea (0.78%). As some DESs outperformed ethanol, the popular solvent for extracting cannabinoids, DESs are viable candidates to replace organic solvents.

Cancers of the head and ne¬ck and their treatment can cause disfigurement and loss of functioning, with a profound negative impact on the person’s self-image and psychosocial wellbeing. This can lead to experiences of shame and stigma, which are important targets for psychosocial interventions. Accurate measurement and identification of these problems enables clinicians to offer appropriate interventions and monitor patients’ progress. This study aimed to validate the Canadian version of the Shame and Stigma Scale (SSS) among French and English speaking head and neck cancer patients. Data from 258 patients from two major Canadian hospitals was analysed. The existing 4-factor structure of the SSS was supported, with the following subscales: Shame with Appearance, Sense of Stigma, Regret, and Social/Speech Concerns. The Canadian SSS showed adequate convergent and divergent validity and test-retest reliability. Rasch analysis suggested scale improvement by removing two misfitting item and two items with differential functioning between French and English speaking patients. The final 16-item scale version had adequate fit to the Rasch model. The SSS provides more accurate measures for people with high levels of shame and stigma, and thus has utility in identifying patients with more severe symptoms who may be in need of psychosocial interventions.

Advanced cutaneous melanoma is considered the most aggressive type of skin cancer with variable rates of treatment response. Nowadays, there are available some classes of immunotherapy and target therapy for its treatment. Immunotherapy can inhibit tumor growth and its recurrence by triggering host's immune system, while targeted therapy acts inhibiting specific molecules or signaling pathways. However, melanoma response to these treatments are highly heterogenous, and frequently become resistant. Epigenome (DNA/histone modification) contribute to cancer initiation and progression. Epigenetic alterations are divided into four levels of gene expression regulation: DNA methylation, histone modification, chromatin remodeling and non-coding RNAs regulation. The deregulation of lysine methyltransferase enzymes is associated with tumor initiation, invasion, development of metastases, changes in immune microenvironment and drug resistance. The study of lysine histone methyltransferase (KMT) inhibitors is important to cancer epigenetic mechanisms understanding and to biological processes. In addition to immunotherapy and target therapy, the research and development of KMT inhibitors is ongoing. Many studies are exploring the therapeutic implications and possible side effects of these compounds, besides their adjuvant potential to the approved current therapies. Importantly, as with any drug development, safety, efficacy, and specificity are crucial considerations when developing KMT inhibitors for clinical applications.

Childhood obesity is one of the most prevalent public health challenges in the United States and although rates are declining overall, rates among children living in underserved neighborhoods are increasing. This five-year intervention project seeks to empower teachers (n=92) to invest in their own health and then to integrate nutrition concepts into core subjects’ lessons in elementary schools. The professional development sessions reflect the concepts in the Whole Child, Whole School, Whole Community model. Results indicate that teachers who attended professional development sessions were more likely to implement nutrition lessons in the classroom (r = 0.54, p&lt;0.01) and students demonstrated a significant increase in nutrition knowledge (p &lt; .001, df = 2, F = 9.66). Investing in school-based programs that ensure teacher well-being and professional development can yield positive benefits for both teachers and students.

The emergence of the COVID-19 pandemics prompted a fast development of novel diagnostic methods of the etiologic virus SARS-CoV-2. Methods based on CRISPR-Cas systems have been particularly promising because they can achieve a similar sensitivity and specificity to the golden standard RT-qPCR, especially when coupled to an isothermal pre-amplification step. Furthermore, they have also solved inherent limitations of RT-qPCR that impede its decentralized use and deployment in the field, such as the need for expensive equipment, high cost per reaction, and delivery of results in hours, among others. In this review, we evaluate publicly available methods to detect SARS-CoV-2 that are based on CRISPR-Cas and isothermal amplification. We critically analyze the steps required to obtain a successful result from clinical samples and pinpoint key experimental conditions and parameters that could be optimized or modified to improve clinical and analytical outputs. The COVID outbreak has propelled intensive research in a short time, which is paving the way to develop effective and very promising CRISPR-Cas systems for the precise detection of SARS-CoV-2. This review could also serve as an introductory guide to new labs delving into this technology.

In this paper we explore how we can use catchment resilience as a unifying concept to manage and regulate catchments, using structured reviews to support our perspective. River catchments are physical boundaries which delineate where all surface water (e.g. precipitation, snow, meltwater) falling on a piece of land runs off or flows to a single point at a lower elevation, where the river meets a larger body of water (e.g. sea, lake). Catchments are complex systems with interrelated natural, social, and technical aspects. The exposure, vulnerability, and resilience of these aspects (separately and in combination) are the latent conditions which when triggered by a specific hazard, result in catchment impacts. In complex catchment systems, resilience is the ability to bounce-back, the ability to absorb, and the ability to transform. When all three abilities are accounted for, we are forced to consider the interactions of the catchment system. Six main complexity concepts can be used to frame how we approach evaluating catchment resilience. These concepts are: natural-social-technical aspects, interactions, spatial scales, time scales, multiple forms of evidence, and uncertainty. In analysing these complexity concepts we have found that there are several gaps in current practice. For example critical interactions which need further methodological study are the linkages between the natural-social-technical realms, as well as across spatial scales (e.g. households or communities) and time scales (e.g. days or years). Requirements for future methodological approaches are suggested. Central to these is (1) the study of interactions linking the short- to medium-term time scales (2) better integration of bottom-up and top-down approaches, to link local context with higher-level decision-making, and (3) developing ‘hazard-agnostic’ methods which can address the impacts of floods, droughts – even acknowledging dormant ‘socio-technical hazards’. There is no ‘one size fits all’ approach to catchment resilience. Mixed method approaches are required and their selection will depend on contextual issues identified early in the process for specific catchments. Central to any effective approach is the incorporation of a linking systems or interaction analysis, which draws together the natural-social-technical system in a meaningful way. If our approaches do not begin to acknowledge the interdependencies and interactions, we may miss substantial opportunities to enhance catchment resilience.

The ejido system in Mexico based on communal land was transformed for private ownership due to neoliberal trends during 1990. This research describes the evolution of Mexican land policies that changed the ejido system into private development to answer why land tenure change is shaping urban growth. To demonstrate this, municipalities of San Andrés Cholula and Ocoyucan were selected as a case study. Within this context, we evaluated how much ejido land is being urbanized due to real estate market forces and what type of urbanization model is created. These two areas represent different development scales: S.A. Cholula where its ejidos were expropriated as part of a regional urban development plan; and Ocoyucan where its ejidos and rural land were reached by private developers without local planning. To analyze both municipalities, historical satellite images from Google Earth were used with GRASS GIS 7.4 and corrected with QGIS 2.18. We found that privatization of ejidos fragmented and segregated the rural world for the construction of massive gated-communities. Therefore, a disturbing land tenure change occurred during the last 30 years, hence this research questions the role of local authorities in permitting land use change without regulations or local planning. The resulting urbanization model is a private sector development that isolates rural communities in their own territories, for which we provide recommendations.

The exploration of heath data by clustering algorithms allows to better describe the populations of interest by seeking the sub-profiles that compose it. This therefore reinforces medical knowledge, whether it is about a disease or a targeted population in real life. Nevertheless, contrary to the so-called conventional biostatistical methods where numerous guidelines exist, the standardization of data science approaches in clinical research remains a little discussed subject. This results in a significant diversity in the execution of data science projects, whether in terms of algorithms used, reliability and credibility of the designed approach. Taking the path of parsimonious and judicious choice of both algorithms and implementations at each stage, this paper proposes Qluster, a practical workflow for performing clustering tasks. Indeed, this workflow makes a compromise between (1) genericity, as it is suitable regardless of the data volume (small/big) and regardless of the nature of the variables (continuous/qualitative/mixed), (2) ease of implementation, as it is based on few easy-to-use software packages, and (3) robustness, through the stability evaluation of the final clusters and through recognized algorithms and implementations. This workflow can be easily automated and/or routinely applied on a wide range of clustering projects. A synthesis of the literature on data clustering as well as the scientific rationale supporting the proposed workflow is also provided. Finally, a detailed application of the workflow on a concrete use case is provided, along with a practical discussion for data scientists. An implementation on the Dataiku platform is available upon request to the authors.

In the 21st century, three highly pathogenic betacoronaviruses have emerged, with an alarming rate of human morbidity and case fatality. Genomic information has been widely used to understand the pathogenesis, animal origin and mode of transmission of betacoronaviruses in the aftermath of the 2002-03 severe acute respiratory syndrome (SARS) and 2012 Middle East respiratory syndrome (MERS) outbreaks. Furthermore, genome sequencing and bioinformatic analysis have had an unprecedented relevance in the battle against the 2019-20 coronavirus disease 2019 (COVID-19) pandemic, the newest and most devastating outbreak caused by a coronavirus in the history of mankind, allowing the follow up of disease spread and transmission dynamics in near real time. Here, we review how genomic information has been used to tackle outbreaks caused by emerging, highly pathogenic, betacoronavirus strains, emphasizing on SARS-CoV, MERS-CoV and SARS-CoV-2.

Wastewater-based surveillance is emerging as an important tool for COVID-19 pandemic trending. Current methods of wastewater collection, such as grab and auto-composite sampling, have drawbacks that impede effective surveillance, especially from small catchments with limited accessibility. Passive samplers, which are more cost-effective and require fewer resources to process, are promising candidates for monitoring wastewater for SARS-CoV-2. Here, we compared traditional auto sampling with passive sampling for SARS-CoV-2 detection in wastewater. Torpedo-style 3D printed passive sampler device containing both cotton swabs and electronegative filter membranes was used. Between April and June 2021, fifteen passive samplers were placed at a local hospital wastewater outflow alongside an auto sampler. Reverse transcription and quantitative polymerase chain reaction (RT-qPCR) was used to detect SARS-CoV-2 in the samples after processing and RNA extraction. The swab and membrane of the passive sampler showed similar detection rates and Ct values for SARS-CoV-2 RNA for the N1 and N2 gene targets. The passive method performed as well as the grab/auto sampling, with no significant differences between N1 and N2 Ct values. There were discrepant results on two days with negative grab/auto samples and positive passive samples, which might be related to the longer duration of passive sampling in the study. Overall, the passive sampler was rapid, reliable and cost-effective, and could be used as an alternative sampling method for the detection of SARS-CoV-2 in wastewater.

Glutathione (GSH) is an antioxidant that our cells utilize to prevent damage done by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals [1]. Due to its immune role in tuberculosis (TB), GSH is hypothesized to play an important part in the immune response against M. tb. Furthermore, one of the hallmark structures of TB is granuloma formation, which involves many types of immune cells. T cells specifically are a major component and are involved in the release of cytokines and activation of macrophages. GSH acts as an important function in macrophages, natural killer cells, and T cells in modulating their activation, their metabolism, the proper cytokine release, the proper redox activity, and free radical levels. For more susceptible patients with HIV and Type 2 Diabetes, the demand for higher GSH levels is increased. This review compiles reports demonstrating the benefits of GSH in improving the immune cell responses against M. tb infection and the use of GSH as adjunctive therapy for TB.

Rotavirus (RV) replicates within viroplasms, membrane-less electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single and double-stranded virus RNAs, and host components such as microtubules, perilipin-1 and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

The aim of this study was to assess the effect of added cultures of probiotic lactic acid bacteria on physicochemical, textural, and sensory characteristics of fresh cheese as well as their viability. Probiotic strains Lactobacillus acidophilus and L. rhamnosus were evaluated at two inoculation times (before the renneting and salting processes) following a factorial treatment arrangement. The bacterial count (log CFU g-1), acidity determination (% lactic acid), pH and percentage of syneresis were evaluated at 0, 1, 7, 14 and 21 days of refrigerated storage (4–5 °C). The texture profile analysis and an extended preference test were carried out at 21 days of storage. At the end of storage, fresh cheeses containing L. rhamnosus, added prior to the renneting process, had similar acidity values (0.18% lactic acid), pH (5.36) and percentage of syneresis (4.71%) compared to those for the cheeses without probiotics or control. Excluding adhesiveness, no differences were observed in texture profile parameters among the assessed cheeses. The fresh cheese supplemented with L. rhamnosus before the renneting process had a microorganism count greater than 6 logarithmic cycle/g, and the highest preference among treatments. The results from this study suggest that fresh cheese can be an excellent matrix for probiotic microorganisms, in particular L. rhamnosus.

Background/Objectives: Instability is one of the main symptoms in patients with vestibular and neurological disorders and therapeutic exercise interventions are increasing its popularity as a way of treatment for those. Additionally, the limits of stability measurement are known to be a good tool for balance evaluation and monitoring of this interventions. The aim of this work is to understand better how a specific protocol provokes changes on this variable and study the characteristics of those who respond and non-respond to it. Methods: A retrospective study was developed with the data of 40 patients treated in the Otorhinolaryngology department in Clínica Universidad de Navarra (Madrid, Spain). Those had an initial reduction in limits of stability, completed the protocol proposed with home-based and hospital-based exercises with frequent limits of stability remeasurement, and assist to the follow-up retest after 1-2 months. Results: A progressive improvement in limits of stability measure was developed through the intervention and partially retained at follow-up visit. Differences were found between responders and non-responders patients. More specifically an initial measure of the limits of stability was able to differentiate those groups with a cut-off data of 56cm2. Conclusions: The protocol proposed was able to induce motor learning in patients included in this study with good retention after 1-2 months. Besides, there is some variability in how patients respond to the treatment. Age and diagnostic should be considered, and an interesting cut-off data for clinal decision making was found.

The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.

The Transient Receptor Potential Ankyrin 1 (TRPA1) cation channels function as broadly-tuned sensors of noxious chemicals in many species. Recent studies identified four functional TRPA1 isoforms in Drosophila melanogaster (dTRPA1(A) to (D)), but their responses to non-electrophilic chemicals are yet to be fully characterized. Methods: We determined the behavioral responses of adult flies to the mammalian TRPA1 non-electrophilic activators citronellal and menthol, and characterized the effects of these compounds on all four dTRPA1 channel isoforms using intracellular Ca2+ imaging and whole-cell patch-clamp recordings. Results: Wild type flies avoided citronellal and menthol in an olfactory test and this behavior was reduced in dTrpA1 mutant flies. Both compounds activate all dTRPA1 isoforms in the heterologous expression system HEK293T, with the following sensitivity series: dTRPA1(C) = dTRPA1(D) &gt; dTRPA1(A) ≫ dTRPA1(B) for citronellal and dTRPA1(A) &gt; dTRPA1(D) &gt; dTRPA1(C) &gt; dTRPA1(B) for menthol. Conclusions: dTrpA1 was required for the normal avoidance of Drosophila melanogaster towards citronellal and menthol. All dTRPA1 isoforms are activated by both compounds, but the dTRPA1(B) is consistently the least sensitive. We discuss how these findings may guide further studies on the physiological roles and the structural bases of chemical sensitivity of TRPA1 channels.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

Introduction: Young adults are the second largest segment of the immigrant population in the United States (US). Given recent trends in later age of initiation of tobacco use, we examined variation in use of tobacco products by nativity status for this population group. Methods: Our study included young adults 18-30 years of age sampled in the National Health Interview Survey (2015-2019), a nationally representative sample of the US population. We calculated prevalence of use of any and 2 or more tobacco products (cigarettes, cigars, pipes, e-cigarettes, and smokeless tobacco) for foreign-born (n=3,096) and US-born (n=6,811) young adults. Logistic regression models adjusted for age, sex, race-ethnicity, education, and poverty, while accounting for the complex survey design. Results: Foreign-born young adults were significantly less likely to use any tobacco product (Cigarette = 7.3% vs 10.7%; Cigar= 1.8% vs 4.8%; E-cigarette= 2.3% vs 4.5%, respectively; p<0.01) or poly tobacco use (1.9% vs. 4.2%; p<0.01) than US-born young adults. Adjusted regression models showed lower odds of poly tobacco use among the foreign-born than their US-born counterparts (Odds Ratio = 0.41, (95% Confidence Interval: 0.26-0.63)). Conclusion: Findings highlight the importance of targeted interventions by nativity status and further tobacco prevention efforts needed for the US-born.

This paper investigates the adaptability of four state-of-the-art Artificial Intelligence (AI) models to the Australian mammographic context through transfer learning, explores the impact of image enhancement on model performance and analyses the relationship between AI outputs and histopathological features for clinical relevance and accuracy assessment. A total of 1712 screening mammograms (n=856 cancer cases and n=856 matched normal cases) were used in this study. The 856 cases with cancer lesions were annotated by two expert radiologists and the level of concordance between their annotations was used to establish image subsets. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of Globally aware Multiple Instance Classifier (GMIC), Global-Local Activation Maps (GLAM), I&amp;H and End2End AI models, both in the pre-trained and transfer learning modes, with and without applying the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm. The four AI models with and without transfer learning in the high-concordance subset outperformed those in the entire dataset. Applying the CLAHE algorithm to mammograms improved the performance of the AI models. In the high-concordance subset with transfer learning and CLAHE algorithm applied, the AUC of the GMIC model was highest (0.912), followed by GLAM model (0.909), I&amp;H (0.893) and End2End (0.875). There were significant differences (P&lt;0.05) in the performances of the four AI models between high-concordance subset and entire dataset. The AI models demonstrated significant differences in malignancy probability concerning different tumour size categories in mammograms. The performance of AI models was affected by several factors such as concordance classification, image enhancement and transfer learning. Mammograms with strong concordance of radiologists’ annotations, applying image enhancement and transfer learning could enhance the accuracy of AI models.

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and is-chemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients so as to prevent and minimize the morbidity of HIBI. Further studies aimed at stand-ardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Proper nutrition is crucial for normal brain and neurocognitive development. Failure to optimize neurodevelopment early in life can have profound long-term implications for both mental health and quality of life. Although the first 1000 days of life represent the most critical period of neurodevelopment, the central and peripheral nervous systems continue to develop and change throughout life. All this time, development and functioning depend on many factors, including adequate nutrition. In this review, we outline the role of nutrients in cognitive, emotional, and neural development in infants and young children with special attention to the emerging roles of polar lipids and high quality (available) protein. Furthermore, we discuss the dynamic nature of the gut-brain axis and the importance of microbial diversity in relation to a variety of outcomes, including brain maturation/function and behavior are discussed. Finally, the promising therapeutic potential of psychobiotics to modify gut microbial ecology in order to improve mental well-being is presented. Here we show that the individual contribution of nutrients, their interaction with other micro-and macronutrients, and the way in which they are organized in the food matrix are of crucial importance for normal neurocognitive development.

Despite the strong links between sleep, circadian rhythms, and mental health, sleep education has been neglected in mental healthcare provider training programs. The current pilot study examined the potential efficacy and acceptability of a sleep education workshop for trainee psychologists, called the Sleep Psychology Workshop. Eleven students completing their Master of Psychology degrees (90% female, 24.4 ± 1.6 years old) attended the Sleep Psychology Workshop as part of their Health Psychology course, delivered as three, two-hour lectures (total six hours). Trainees’ sleep psychology knowledge quiz scores (% correct) demonstrated significant improvement from pre- (M = 60%, SD = .09) to post-workshop (M = 79%, SD = .08), t (6) = -5.18, p = .002. Trainees also reported increased self-efficacy to use common sleep-related assessment instruments and empirically supported interventions to manage sleep and circadian rhythm disturbances, along with increased confidence to manage insomnia disorder in clinical practice (all p<.02). Trainees also endorsed the workshop as an acceptable sleep education program for trainee psychologists via a post-workshop feedback survey, focus group, and six-month follow-up survey. This pilot study provides preliminary evidence for the Sleep Psychology Workshop as an effective and acceptable sleep education program for trainee psychologists.

Objective: Food security during public health emergencies relies on situational awareness of needs and resources. Artificial intelligence (AI) has revolutionized situational awareness during crises, allowing the allocation of resources to needs through machine learning algorithms. Limited research exists monitoring Twitter for changes in the food security-related public discourse during the COVID-19 pandemic. We aim to address that gap with AI by classifying food security topics on Twitter and showing topic frequency per day. Methods: Tweets were scraped from Twitter from January 2020 through December 2021 using food security keywords. Latent Dirichlet Allocation (LDA) topic modeling was performed, followed by time-series analyses on topic frequency per day.Results: 237,107 tweets were scraped and classified into topics, including food needs and resources, emergency preparedness and response, and mental/physical health. After the WHO’s pandemic declaration, there were relative increases in topic density per day regarding food pantries, food banks, economic and food security crises, essential services, and emergency preparedness advice. Threats to food security in Tigray emerged in 2021.Conclusions: AI is a powerful yet underused tool to monitor food insecurity on social media. Machine learning tools to improve emergency response should be prioritized, along with measurement of impact. Further food insecurity word patterns testing, as generated by this research, with supervised machine learning models can accelerate the uptake of these tools by policymakers and aid organizations.

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anticancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50kDa), medium (MMW, 50-100kDa) and high (HMW, >100kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had highest the levels of sugars, acids and sulphation among molecular weight fractions. There was a dose dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in sub G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress induced apoptosis-like cell death for F. vesiculosus fucoidan but features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.

Acerola (Malpighia spp.) is a tropical plant genus of shrubs and trees whose fruit is rich in nutrients and bioactive compounds. However, its production generates significant waste that could pose an environmental issue. This review aims to summarize recent research on the potential uses of acerola wastes, including the extraction of bioactive compounds such as polyphenols, carotenoids, and pectins, as well as the development of materials such as nanomaterials, chitosan, and biofuels. Additionally, the paper discusses the potential medical applications of acerola wastes, such as wound healing, antioxidant, and anticancer effects. Finally, the paper explores the challenges and opportunities of using acerola waste as a sustainable source of raw materials and energy. The findings suggest that acerola waste could be a valuable resource for developing high-value products and promoting sustainable production practices in the fruit industry.

Pineapple is a highly demanded fruit in international markets, thanks to its unique appearance and flavor, high fiber content, vitamins, folic acid, and minerals. It makes the pineapple production and processing market a significant source of income for producing countries, such as Costa Rica. Nowadays, its processing produces a large amount of waste with negative consequences for the environment. However, pineapple waste is an essential source of cellulose, hemicellulose, lignin, and other high-value products like enzymes (bromelain). These by-products can be obtained by pineapple waste biorefinery, generating an additional source of export goods and foreign currency, framing pineapple processing in the concept of the circular economy. This review discusses how incorporating biorefinery in the pineapple production processes can contribute to the post-COVID 19 economy in Costa Rica. Pineapple production in Costa Rica is explored, and the contamination of generated residues is delineated. Furthermore, the primary processes for by-product extraction via biorefinery, their general characteristics and applications in the medical field, and their contribution to the circular economy are presented.

There has been significant increase of studies investigating plasma biomarkers of Alzheimer’s and their relationship to cognitive functioning. The impact of ethnicity on this relationship has not been extensively studied. The current research investigated the relationship between the plasma biomarkers of total tau, Aβ40, Aβ42 and NfL and neuropsychological test performance in a bi-ethnic sample of cognitively unimpaired, older community dwelling adults. The 1326 cognitively unimpaired participants drawn from The Health & Aging Brain Study – Health Disparities (HABS-HD) study included 765 Mexican American participants and 860 non-Hispanic White participants with complete plasma biomarkers and neuropsychological testing. Plasma samples were assayed using Simoa technology. Significant differences in concentrations were found for all of the plasma biomarkers. NHWs had significantly higher levels of each of the biomarkers with a lower Aβ42/ Aβ40. With none of the biomarkers related to performance on any of the neuropsychological tests. For MAs, Aβ40 was the only biomarker that was significantly related to neuropsychological test performance. Aβ40 levels were negatively related to performance on Trails A, Trails B and Digit Symbol Substitution. Results suggest that the relationship of these biomarkers to cognitive functioning is impacted by ethnicity and may be domain specific.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

In recent times, a great interest has been motivated in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, lupane-type triterpenes are phytochemicals that exert significant activities against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose‐limiting toxic effects and chemoresistance. Herein, we investigated the structure-activity relationship of six pentacyclic triterpenes: oleanolic acid (OleA), ursolic acid (UrA), asiatic acid (AsA), betulinic acid (BeA), betulin (Betu), lupeol (Lupe), on NSCLC A549 cells. From our studies, we confirmed that all these triterpenes showed cytotoxicity in the mid µM range, where BeA showed the strongest effect. Then, we determined that most of these triterpenes induced S-phase and G2/M phase cycle arrest, reactive oxygen species, mitochondrial depolarization, and caspase 3 activation. For chemoresistance markers, we elucidated that most triterpenes downregulated STAT3 and PDL1 genes. In contrast, ursane-type UrA and AsA also induced DNA damage, reactive nitrogen species and autophagy. These results showed that even slight structural changes in these triterpenes can influence the cellular response and mechanistic pathways. This study opens promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids.

The prevalence and incidence of cardiac pro-arrhythmic disorders are often influenced by sex due to specific effects on the QT interval. Androgens shorten QT, which may be protective against acquired long QT syndromes and their related arrhythmias in men such as torsade de pointes (TdP). On the other hand, androgens can potentiate Brugada and early repolarization syndromes, which are most prevalent in men. In this case series, we highlight four male patients with aborted SCD in the setting of abnormal testosterone status; two patients with TdP in a setting of testosterone deprivation (of which one drug-induced) and 2 patients with ventricular fibrillation associated with exogenous androgenic booster (Tribulus terrestris) intake. From this case series, we review the current available literature of the effects of androgen as a double-edged sword on the QTc interval and emphasize the importance of QTc monitoring in this subset of patients.

Thin supported inorganic mesoporous membranes are used for removal of salts, small molecules (PFAS, dyes, polyanions) and particulate species (oil droplets) from aqueous sources with high flux and selectivity. Nano-filtration membranes can reject simple salts with 80-100% selectivity through a space charge mechanism. Rejection by size selectivity can be near 100% since the membranes can have a very narrow size distribution. Mesoporous membranes have received par-ticular interest due to their (potential) stability at operational conditions and defouling operations. More recently membranes with extreme stability became interesting with the advent of in-situ fouling mitigation by means of ultrasound, emitted from within the membrane structure. For this reason we explored the stability of available and new membranes with accelerated lifetime tests in aqueous solutions at various temperatures and pH values. Of the available ceria, titania, mag-netite membranes none were actually stable at all test conditions. In earlier work, it was already established that meso-porous alumina membranes have very poor stability. A new nano-filtration membrane was made of cubic zirconia membranes that exhibited a near perfect stability. A new ultra-filtration membrane was made of amorphous silica that was fully stable in ultrapure water at 80°C. This work provides details of membrane synthesis, stability characterization and actual sta-bility data.

The Peripheral giant cell granuloma (PGCG) is an asymptomatic, non-neoplastic and proliferative lesion of unknown etiology. Some possible pre-disposing factors such as hormonal changes dur-ing pregnancy, have been suggested. However, the association between PGCG and pregnancy is controversial. There are few reported clinical cases of pregnancy-associated PGCG in the litera-ture, and they occurred only in the lower jaw. The present report is on a 35-year-old female pa-tient at 36 weeks of gestation who presented with a PGCG in the central and lateral incisors of the upper jaw. The management consisted of surgical excision, along with curettage of the affected bony walls. The diagnosis was based on clinical results and imaging examinations, and it was histopathologically confirmed. The patient underwent postoperative follow-up evaluations at 3, 6 and 12 months, and there were no signs of recurrence.

Background: Machine learning has revolutionized situational awareness during disaster management by classifying, clustering, and predicting impacted locations and people. Despite its importance, no review has been conducted on machine learning tools for food assistance efforts during emergency or non-emergency situations. The purpose of this scoping review is to address that gap. Methods: Keywords were defined within the concepts of food assistance and machine learning. After the database searches, PRISMA guidelines were followed to perform a partnered, two-round scoping literature review. Text mining and Latent Dirichlet Allocation topic modeling algorithms were used to determine trends. Results: 28 articles met criteria and were included in the analysis. The types of study designs included: model development (42.9%), non-study (i.e., text and opinion) (28.6%), qualitative research (14.3%), case study (10.7%), and meta-analysis (3.6%). There were no quantitative studies. The machine learning tools’ main functions were improving SNAP programs (32.1%), detecting needs and resources (25%), predicting food insecurity (21.4%), and situational awareness of current food insecurity issues (21.4%). None of these studies took place during a disaster or explicitly addressed emergency mitigation, preparedness, or recovery. All of the studies were in early phases of development and implementation. Conclusion: Machine learning tools for improving situational awareness, resource allocation, policymaking, and prediction have the potential to improve food assistance, but there is a lack of implementation and evaluation during all disaster phases. Also needed is more formative work on generating food-related queries and defining variables and features of food security.

Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Materials & Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of 10 control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR) methods. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

Understanding the dynamics of humoral immune responses throughout the COVID-19 pandemic is crucial for optimizing vaccine strategies. This study aimed to investigate the impact of infection and vaccine-induced immunity on the Albanian population from August 2021 to August 2022. Two independent samples from the Albanian general population were analyzed using an ELISA method to assess IgG class anti-Spike (S1) and anti-Nucleocapsid (N) SARS-CoV-2 antibodies. The results revealed a robust immune response among vaccinated individuals with prior COVID-19 infection who received only one vaccine dose. In the 2022 cohort, most individuals who received one vaccine dose achieved comparable seropositivity and antibody levels to those who received two doses. However, individuals aged 61 and over required two or three vaccine doses to reach the same level of immune response as the younger population. Notably, the time elapsed since infection or vaccination did not significantly impact the immune response. These findings highlight the importance of hybrid immunity and suggest that one vaccine dose may be sufficient for most individuals with prior COVID-19 infection. However, additional doses are necessary for optimal protection in older individuals. This study provides unique insights into humoral immune response dynamics that can be used to refine ongoing COVID-19 population vaccination strategies for middle-income countries with low vaccination coverage.

The major stress-inducible Hsp70 (HSPA1A) is overexpressed in the cytosol of many highly aggressive tumor cells including glioblastoma multiforme and presented on their plasma membrane. Depending on its intracellular or membrane localization, Hsp70 either promotes tumor growth or serves as a target for NK cells. The kinetics of the membrane Hsp70 (mHsp70) density on human glioma cells (U87) was studied after different irradiation doses to define the optimal therapeutic window for Hsp70-targeting NK cells. To maintain the cells in the exponential growth phase during a cultivation period of 7 days different initial cell counts were seeded. Although cytosolic Hsp70 levels remained unchanged on days 4 and 7 after a sublethal irradiation with 2 Gy, 4 Gy and 6 Gy, a dose of 2 Gy resulted in an upregulated mHsp70 density in U87 cells which peaks on day 4 and starts to decline on day 7. Higher radiation doses (4 Gy, 6 Gy) resulted in an earlier and more rapid onset of the mHsp70 expression on days 2 and 1, respectively, followed by a decline on day 5. Membrane Hsp70 levels are higher in G2/M than in G1, however, an irradiation-induced cell cycle arrest on days 4 and 7, was not associated with an increase in the mHsp70 density. Extracellular Hsp70 concentrations increased significantly compared to sham (0 Gy) irradiated cells on days 4 and 7 but not on day 1. Functionally, elevated mHsp70 densities were associated with a significantly better lysis by Hsp70-targeting NK cells. In summary, the kinetics of changes in the mHsp70 density upon irradiation on tumor cells is time- and dose-dependent.

African swine fever virus (ASFV) is the causative agent of African swine fever, an economically important disease of pigs, often with a high case fatality rate. ASFV has demonstrated low genetic diversity among isolates collected within Eurasia. To explore the influence of viral variants on clinical outcomes and infection-dynamics in pigs experimentally infected with ASFV, we have designed a deep sequencing strategy. Variant analysis revealed 3 distinct SNPs present in the virus inoculum (at 2.4%, 0.7%, and 13% frequency, respectively) that were maintained within all infected pigs (1-6 % frequency, and the latter at 16-21%). Several pigs displayed other unique SNPs at &lt;10% frequency. In addition, a deletion of 10487 bp (resulting in the complete loss of 21 genes) was present at nearly 100% frequency in the ASFV DNA from one pig at position 6362-16849. This deletion was also found to be present at low levels in the virus inoculum and in two other infected pigs. The current methodology can be used for the currently circulating Eurasian ASFVs and also adapted to other ASFV strains and genotypes. Comprehensive deep sequencing is critical for following ASFV molecular evolution, especially for identification of modifications that affect virus virulence.

The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite’s strong dependence on this pathway and significant structural differences of its glycolytic enzymes compared to their human counterpart, glycolysis is considered as a potential drug target. In this study, we provide the first three-dimensional protein structure of P. falciparum hexokinase (PfHK), containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion which lines the active site. Moreover, we propose that this insertion plays a role upon ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both Sglutathionylation and Snitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.

The parasitic mite, Varroa destructor, has shaken the beekeeping and pollination industries since its spread from its native host, the Asian honey bee (Apis cerana), to the naïve European honey bee (A. mellifera) used commercially for pollination and honey production around the globe. Varroa is the greatest threat to honey bee health. Worrying observations include increasing acaricide resistance in the varroa population and sinking economic treatment thresholds, suggesting that the mites or their vectored viruses are becoming more virulent. Highly infested weak colonies facilitate mite dispersal and disease transmission to stronger and healthier colonies. Here, we review recent developments in the biology, pathology and management of varroa, and integrate older knowledge that is less well known.

Purpose: To create a highly balanced comparison of ab interno trabeculectomy (Trabectome, AIT) and trabecular bypass stenting (iStent, TBS).Setting: Eye and Ear Institute, Pittsburgh, Ross Eye Institute, Buffalo, and Glaucoma Associates of Texas, Dallas, USA.Design: Retrospective Exact Matching analysis.Methods: AIT and TBS patients were included from three large glaucoma practices. The primary outcome measure was the unmedicated IOP ≤ 21 mmHg at 2-year follow-up visit. A secondary measure was unmedicated IOP reduction ≥ 20% at 2 years. Patients were matched by baseline IOP, the number of glaucoma medications and glaucoma type using Exact Matching and by age using Nearest Neighbor matching. Patients without a close match were excluded. All surgeries were combined with phacoemulsification. Results: 154 AIT and 110 TBS eyes were analyzed. 48 AIT patients were exactly matched to 48 TBS patients. Both groups had a baseline IOP of 15.3±3.1 mmHg. At 24 months, the mean IOP was 13.9±3.3 for AIT versus 16.8±2.8 mmHg for TBS (p=0.04), while the number of medications was 0.7±1.0 for AIT versus 1.7±1.2 for TBS (p=0.04). The proportion of subjects achieving IOP ≤ 21 mmHg without medications at 24 months was 53% in AIT versus 16.6% in TBS (P < 0.05). At 24-month follow up 17.6% of patients in AIT had ≥ 20% IOP reduction without medication versus no patient in TBS. Conclusions: An Exact Matching comparison of AIT and TBS demonstrated greater IOP reduction with fewer medications in AIT.

The main objective of this work was to evaluate the application of individual and ensemble machine learning models to classify malignant and benign breast masses using features from two-dimensional (2D) correlated spectroscopy spectra extracted from five-dimensional Echo Planar-Correlated Spectroscopic Imaging (5D EP-COSI) and Diffusion-weighted imaging (DWI). Twenty-four different metabolite and lipid ratios with respect to 2D diagonal peaks at 1.4ppm and 5.4ppm, and water from one-dimensional non-water-suppressed (NWS) spectra were used as the features. Additionally, water fraction, fat fraction and water-to-fat ratios from NWS spectra and apparent diffusion coefficients (ADC) from DWI were included. Nine most important features were identified using recursive feature elimination. XGBoost (AUC:93.0%, Accuracy:85.7%, F1-score:87.6%), GradientBoost (AUC:94.4%, Accuracy:87.0%, F1-score:89.4%), CatBoost (AUC:95.2%, Accuracy:86.9%, F1-score:88.4%) and RandomForest (AUC:92.2%, Accuracy:85.3%, F1-score:87.6%) were the best performing models. While the conventional biomarkers like choline, myo-Inositol, and glycine were statistically significant predictors, the key features contributing to the classification were ADC, 2D diagonal peaks at 0.9ppm, 2.1ppm and 2.3ppm, cross peaks between 1.4 and 0.9ppm, 4.3 and 4.1ppm, 2.1 and 1.4ppm and the triglyceryl-fat cross peak. The results highlight the contribution of the 2D spectral peaks to the model, and they demonstrate the potential of 5D EP-COSI for early breast cancer detection.

Pineapple is a highly demanded fruit in international markets, thanks to its unique appearance and flavor, high fiber content, vitamins, folic acid, and minerals. It makes the pineapple production and processing market a significant source of income for producing countries, such as Costa Rica. Nowadays, its processing produces a large amount of waste with negative consequences for the environment. However, pineapple waste is an essential source of cellulose, hemicellulose, lignin, and other high-value products like enzymes (bromelain). These by-products can be obtained by pineapple waste biorefinery, generating an additional source of export goods and foreign currency, framing pineapple processing in the concept of the circular economy. This review discusses how incorporating biorefinery in the pineapple production processes can contribute to the post-COVID 19 economy in Costa Rica. Pineapple production in Costa Rica is explored, and the contamination of generated residues is delineated. Furthermore, the primary processes for by-product extraction via biorefinery, their general characteristics and applications in the medical field, and their contribution to the circular economy are presented.

Novel sensing technologies for liquid biopsies offer a promising prospect for the early detection of metabolic conditions through -omics techniques. Indeed, high-field NMR facilities are routinely used for metabolomics investigations on a range of biofluids in order to rapidly recognize unusual metabolic patterns in patients suffering from a range of diseases. However, these techniques are restricted by the prohibitively large size and cost of such facilities, suggesting a possible role for smaller, low-field NMR instruments in biofluid analysis. Herein we describe selected biomolecule validation on a low-field benchtop NMR spectrometer (60 MHz), and present an associated protocol for the analysis of biofluids on compact NMR instruments. We successfully detect common markers of diabetic control at low-to-medium concentrations through optimized experiments, including glucose (≤ 2.6 mmol./L) and acetone (25 μmol./L), and additionally in readily-accessible biofluids. We present a combined protocol for the analysis of these biofluids with low-field NMR spectrometers for metabolomics, and offer a perspective on the future of this technique appealing to point-of-care applications.

Despite needs for new therapies and improvements in existing approaches in cardiovascular, pulmonary, endocrine, and renal disease, investment in these areas is lagging relative to other specialties. This article summarizes a meeting of key stakeholders of U.S. Food and Drug Administration (FDA) officials, representatives from academia, national organizations, and patients and caregivers. The purpose was to identify and discuss high-priority issues, establish areas of common interest, and explore opportunities for collaboration. During the meeting (September 2016), the construct of a “multimorbidity continuum” emerged, in which chronic diseases are understood as their effects on the whole rather than individual organ systems. Cross-disciplinary priorities included: 1) the need to generate greater high-quality evidence at lower cost; 2) the imperative to develop and implement patient-centered approaches to clinical investigations; 3) the importance of trial participation in under-represented populations, particularly with comorbid conditions, and 4) the need for progress in tobacco regulation. Representatives from each therapeutic area reported on their consensus priorities, and FDA representatives discussed the agency’s role in facilitating broader approaches to therapeutic development and evaluation of disease as linked across organ systems rather than in isolation, and emphasized the importance of patient engagement, collaboration and communication across stakeholders.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR=11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Amazon Simple Storage Service (Amazon S3) has become a widely used and reliable platform for storing large biomedical datasets. However, unintended changes to the original data can occur during the data writing and transmission, ultimately altering the original contents of the object transferred and producing unexpected results when later accessed. Despite the interest in verifying end-to-end data integrity, there are no existing open-source and easy-to-use tools to accomplish this mission. To bridge this gap, here we present aws-s3-integrity-check, a user-friendly, lightweight and reliable bash tool to verify the integrity of a dataset stored within an Amazon S3 bucket. By using this tool, we completed the integrity verification of 1,045 records ranging between 5 Bytes and 10 Gigabytes (GB) in size and occupying a total of ~935 GigaBytes (GB) of Amazon S3 cloud storage space in ~114 minutes. The aws-s3-integrity-check tool also provides file-by-file on-screen and log-file-based information about the status of each individual integrity check. To the best of our knowledge, the aws-s3-integrity-check bash tool is the only open-source tool that allows verifying the integrity of a dataset uploaded to the Amazon S3 Storage system in a quick, reliable and efficient manner. The aws-s3-integrity-check tool is freely available for download and use at https://github.com/SoniaRuiz/aws-s3-integrity-check and https://hub.docker.com/r/soniaruiz/aws-s3-integrity-check.

Sonoran felids are threatened by drought and habitat fragmentation. Vector range expansion and anthropogenic factors such as habitat encroachment and climate change are altering viral evolutionary dynamics and exposure. However, little is known about the diversity of viruses present in these populations. Small felid populations with lower genetic diversity are likely to be most threatened with extinction by emerging diseases, as with other selective pressures, due to having less adaptive potential. We used a metagenomic approach to identify novel circoviruses, which may have a negative impact on the population viability, from confirmed bobcat (Lynx rufus) and puma (Puma concolor) scats collected in Sonora, Mexico. Given some circoviruses are known to cause disease in their hosts, such as porcine and avian circoviruses, we took a non-invasive approach using scat to identify circoviruses in free-roaming bobcats and puma. Three circovirus genomes were determined, and, based on the current species demarcation, they represent two novel species. Phylogenetic analyses reveal that one circovirus species is more closely related to rodent associated circoviruses and the other to bat associated circoviruses, sharing the highest genome-wide pairwise identity of approximately 70% and 63%, respectively. At this time, it is unknown whether these scat-derived circoviruses infect felids, their prey, or another organism that might have had contact with the scat in the environment. Further studies should be conducted to elucidate the host of these viruses and assess health impacts in felids.

This retrospective study assesses the efficacy and tolerability of anti-CGRP therapy in adolescents and young adults (ages 12-21) with migraines and chronic daily headaches unresponsive to standard treatments. Migraines severely affect school performance, self-esteem, psychological well-being, and cognitive health in this demographic, who are also sensitive to the side effects of conventional medications often prescribed off-label and face high insurance denial rates. Medication overuse, including analgesics, triptans, and NSAIDs, is prevalent due to treatment failures. Elevated plasma CGRP levels during migraines suggest that anti-CGRP therapies, which have shown success in adults, might benefit this age group. Over three years, patients at a specialized headache center were evaluated for the impact of anti-CGRP treatments, including monoclonal antibodies (erenumab, fremanezumab, galcanezumab) and small molecule CGRP receptor antagonists (ubrogepant, rimegepant, atogepant), either alone or in combination with OnabotulinumtoxinA. The study found significant improvements in migraine management, especially among older adolescents, with reduced rescue medication use and emergency visits. Longer treatment courses and combination therapy with traditional medications were more effective than monotherapy, reducing migraine intensity and frequency. Adverse effects were minimal, and no significant medication interactions were noted. Anti-CGRP therapy demonstrates substantial potential in improving outcomes for this age group with chronic and episodic migraines.

Glioblastoma (GBM) is the most common primitive tumor in adult central nervous system (CNS), classified as grade IV according to WHO 2016 classification. GBM shows a poor prognosis with an average survival of approximately 15 months, representing an extreme therapeutic challenge. One of its distinctive and aggressive features is aberrant angiogenesis, which drives tumor neovascularization, representing a promising candidate for molecular target therapy. Although several pre-clinical studies and clinical trials have shown promising results, anti-angiogenic drugs have not led to a significant improvement in overall survival (OS), suggesting the necessity of identifying novel therapeutic strategies. Metformin, an anti-hyperglycemic drug of the Biguanides family, used as first line treatment in Type 2 Diabetes Mellitus (T2DM), demonstrated in vitro and in vivo antitumoral efficacy in many different tumors, including GBM. From this evidence, a process of repurposing of the drug has begun, leading to the demonstration of the inhibition of various oncopromoter mechanisms and, consequently, to the identification of the molecular pathways involved. Here, we review and discuss the potential metformin’s antitumoral effects on GBM, inspecting if it could properly act as an anti-angiogenic compound to be considered as a safely add-on therapy in the treatment and management of GBM patients.

In contrast to normal cells, tumor cells of multiple entities overexpress the Heat Shock Protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane-Hsp70 positive tumor cells actively release Hsp70 into lipid microvesicles termed exosomes into the blood. Due to conformational changes of Hsp70 in the lipid environment, most commercially available antibodies fail to detect membrane-bound and exosomal Hsp70. To fill this gap and to assess the role of exosomal Hsp70 in the circulation as a potential tumor biomarker, we established the novel complete Hsp70 (compHsp70) sandwich ELISA using two monoclonal antibodies (mAbs) that are able to recognize both, free and lipid-associated Hsp70 on the cell surface of viable tumor cells and exosomes. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70, with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/ml, high recovery rates of ‘spiked’ liposomal Hsp70 (>84%), comparable values between human serum and plasma samples, and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy volunteers. Hsp70 concentrations dropped concomitantly with the decrease in viable tumor mass on irradiation of patients with approximately 20 Gy (range 18 – 22.5 Gy) or after completion of radiotherapy (60 - 70 Gy). In summary, the compHsp70 ELISA presented herein provides a highly sensitive and reliable tool for measuring free and exosomal Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a predictive tumor-specific biomarker, risk assessment and for monitoring therapeutic outcome.

Bioenergy with carbon capture and sequestration (BECCS) is one strategy to remove CO2 from the atmosphere. To assess the potential scale and cost of CO2 sequestration from BECCS in the US, this analysis models carbon efficiencies and costs of biomass production, delivery, power generation, and CO2 capture and sequestration in saline formations. The analysis includes two biomass supply scenarios (near-term and long-term), two biomass logistics scenarios (conventional and pelletized), two generation technologies (pulverized combustion and integrated gasification combined cycle), and three cost accounting scenarios (gross cost, net cost after electricity revenues, and net cost after electricity revenues with avoided emissions from conventional power generation). Results show cost Mg-1 CO2 as a function of CO2 sequestered (simulating capture up to 90% of total CO2 sequestration potential) and associated spatial distribution of resources and generation locations for the array of scenario options. Under a near-term scenario using 222 million Mg yr-1 of biomass, up to 196 million Mg CO2 can be sequestered at scenario-average costs ranging from $60 to $158 Mg 1 CO2; under a long-term scenario using 823 million Mg yr-1 of biomass, up to 727 million Mg CO2 yr 1 can be sequestered at scenario-average costs ranging from $32 to $242 Mg-1 CO2. These costs are largely influenced by cost accounting scenario, and the CO2 sequestration potential may be reduced if future competing demand reduces resource availability. Results suggest there are multiple feedstock-logistics-generation pathways toward CO2 drawdown that could be incrementally trialed and monitored for environmental sustainability effects. Interactive visualization of results is available at [final link to be determined].

A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments, such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of pharmacoresistance in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We compared the group of patients with controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p &lt; 0.05). In addition, lipoproteins (p = 0.05), lactate (p = 0.05), glucose (p = 0.05), unsaturated lipids (p = 0.05), isoleucine (p = 0.05), and proline (p = 0.05), could discriminate between the two groups of patients classified according to response to ASM. The identified metabolites were linked to different biological pathways related to cell energy metabolism, and pathways linked to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In contrast, we found that pyruvate metabolism may be linked to resistance to ASM. In conclusion, in addition to insights into the mechanisms underlying MTLE and the response to treatment with ASM, our results suggest that plasma metabolites may be used as biomarkers of disease and response to ASM in patients with MTLE. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE.

Children with severe acute malnutrition (SAM) are at high risk of impaired development. Contributing causes include inadequate intake of specific nutrients such as polyunsaturated fatty acids (PUFA) and lack of adequate stimulation. We conducted a pilot study assessing developmental and nutritional changes in children with SAM provided with a modified ready-to-use therapeutic food and a context-specific psychosocial intervention in Mwanza, Tanzania. We recruited 82 children with SAM (6-36 months) and 88 sex- and age-matched non-malnourished children. We measured child development, using the Malawi Development Assessment Tool (MDAT), measures of family and maternal care for children, and whole blood PUFA levels. At baseline, the mean total MDAT z-score of children with SAM was lower than non-malnourished children; -2.37 (95% confidence interval: -2.92; -1.82) as was their total n-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels. After 8 weeks’ intervention, MDAT z-scores improved in all domains, especially fine motor, among children with SAM. Total n-3, and EPA levels increased, total n-6 fatty acids decreased, and DHA remained unchanged. Family and maternal care also improved. The suggested benefits of the combined interventions on developmental and nutritional status of children with SAM will be tested in a future trial.

The unprecedented COVID-19 pandemic posed major challenges to local, regional, and global economies and health systems, and fast clinical diagnostic workflows were urgently needed to contain the spread of SARS-CoV-2. Here, we describe the platform and workflow established at the Cornell COVID-19 Testing Laboratory (CCTL) for high-throughput testing of clinical samples from the university and the surrounding community. This workflow enabled efficient and rapid detection, and successful control of SARS-CoV-2 infection on campus and its surrounding communities. Our cost-effective and fully automated workflow enabled testing of over 8,000 pooled samples per day and provided results for over 2 million samples. Automation of time- and effort-intensive sample processing steps such as accessioning and pooling increased laboratory efficiency. Customized software applications were developed to track and store samples, deconvolute positive pools, track and report results and for workflow integration from sample receipt to result reporting. Additionally, quality control dashboards and turn-around time tracking applications were built to monitor assay and laboratory performance. As infectious disease outbreaks pose a constant threat to both human and animal health, the highly effective workflow implemented at CCTL could be modeled to establish regional high-capacity testing hubs for infectious disease preparedness and emergency response.

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study we aimed to investigate prognostic factors based on clinicopathologic findings in a molecular/immunohistochemical confirmed nationwide multicenter cohort of 57 EHE. Patients had unifocal disease (n=29), multifocal disease (n=5), lymph node metastasis (n=8) and/or distant metastasis (n=15) at the time of diagnosis. The overall survival rate was 69.6% at 1 year and 50.5% at 5 years. Survival did not correlate with sex, age or histo-pathological parameters. No survival differences were observed between multifocal and metastatic disease suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al. dividing the cases into low (n=4), intermediate (n=15) and high (n=3) risk-groups. Larger tumor size (>3cm) and higher mitotic count (>1/10HPF) was asso-ciated with progressive unifocal disease course. Lymph node metastases at time of diagnosis oc-curred in 14.0% of the cases and was mainly associated with tumor localization in the head and neck area proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previous described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

Objective: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. Design: Systematic umbrella review of existing meta-analyses. Data Sources: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manually searching reference lists from 2009 to June 2023. Inclusion Criteria: Systematic reviews and meta-analyses of cohort, case-control, and/or cross-sectional study designs that evaluated the associations between exposure to ultra-processed foods and adverse health outcomes in humans across the lifespan. Results: The search identified 45 unique pooled analyses, including 13 dose-response and 32 non-dose-response associations (n=9,888,373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health outcome domains spanning cardiometabolic, gastrointestinal, and respiratory conditions, cancer, mental health, and mortality. Based on a pre-specified evidence classification criteria, convincing evidence (Class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease-related mortality (RR: 1.50; 95%CIs: 1.37 to 1.63), type two diabetes (dose-response RR: 1.12; 95%CIs: 1.11 to 1.13), and depressive outcomes (HR: 1.21; 95%CIs: 1.16 to 1.28), as well as higher risks of prevalent anxiety outcomes (OR: 1.48; 95%CIs: 1.37 to 1.59) and combined common mental disorder outcomes (OR: 1.53; 95%CIs: 1.43 to 1.63). Highly suggestive (Class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all-cause mortality (RR: 1.21; 95%CIs: 1.15 to 1.27), heart disease-related mortality (dose-response HR: 1.66; 95%CIs: 1.51 to 1.84), and type two diabetes (OR: 1.40; 95%CIs: 1.23 to 1.59), together with higher risks of prevalent obesity (OR: 1.55; 95%CIs: 1.36 to 1.77), adverse sleep-related outcomes (OR: 1.41; 95%CIs: 1.24 to 1.60), and wheezing (RR: 1.40; 95%CIs: 1.27 to 1.55). Out of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (Class III-IV) and 13 were graded as no evidence (Class V). Using the GRADE framework, 22 pooled analyses were rated as "Low" quality, with 19 rated as "Very Low” and four rated as "Moderate" quality. Conclusions: Higher exposure to ultra-processed food was associated with a greater risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to evaluate the effectiveness of using population-based measures to target and reduce dietary exposure to ultra-processed foods for improved human health. Systematic Review Registration: PROSPERO CRD42023412732.

Withania somnifera (WS), also known as ashwagandha, is a popular botanical supplement used to treat various conditions including memory loss, anxiety and depression. Previous studies from our group showed an aqueous extract of WS root (WSAq) enhances cognition and alleviates markers for depression in Drosophila. Here, we sought to confirm these effects in the 5xFAD mouse model of β-amyloid (Aβ) accumulation. Six- to seven-month-old male and female 5xFAD mice were treated with WSAq in their drinking water at 0 mg/mL, 0.5 mg/mL or 2.5 mg/mL for four weeks. In the fourth week of treatment, spatial memory, anxiety and depressive-like symptoms were evaluated. At the conclusion of behavioral testing, brain tissue was harvested, immunohistochemistry was performed, and the cortical expression of antioxidant response genes was evaluated. Both concentrations of WSAq improved spatial memory and reduced depressive and anxiety-related behavior. These improvements were accompanied by a reduction in Aβ plaque burden in the hippocampus and cortex and an attenuation of neuroinflammatory markers. Antioxidant response genes were upregulated in the cortex of WSAq treated mice. Oral WSAq treatment could be beneficial as a therapeutic option in AD for improving disease pathology and behavioral symptoms. Future studies focused on dose optimization of WSAq administration and further assessment of the mechanisms by which WSAq elicits its beneficial effects will help inform the clinical potential of this promising botanical therapy.

Background: the devastating outbreak of COVID-19 poses serious challenges for the diagnostics laboratories, which are often facing global shortage of reagents and equipment. With the aim of increasing the diagnostic throughput for SARS-CoV-2 molecular test, the purpose of this study was to validate an additional RNA extraction method respect to those already recommended by WHO and the US Centers for Disease Control and Prevention (CDC). Methods: a new protocol for RNA extraction from nasopharyngeal swab was set up, adapting the Qiagen RNeasy 96 plate and validated on a set of 100 clinical samples analyzed in parallel by Roche-Magnapure method (already recommended by CDC guidelines). Results: the internal control and target genes analysis showed a good agreement between the two extraction methods indicating that the two methods can be considered equivalent and that the RNeasy-adapted method can be applied for the SARS-CoV-2 diagnostics. The addition of this new extraction method resulted in a throughput increase for SARS-CoV-2 molecular test of about 2000 samples/month during the initial months of the pandemic emergency in which the lack of reagents for the extraction led to an insufficient sample processing throughput of the analysis of the swabs.

Study Objective: This study examined office workstation types’ impact on objective health-related metrics including stress, physical activity (PA), and sleep quality. We propose a sensor-based sleep quality index (SB-SQI) to fill a needed gap for objective sleep quality measurement over short timescales. Methods: We monitored 231 office workers using chest-worn sensors for 72 hours, yielding 11,736 hours of usable data from 163 participants (mean age 43.4, 56% women). SB-SQI was based on a validated algorithm estimating sleep-onset latency, total sleep time, and sleep efficiency, using the scoring method from the Pittsburg Sleep Quality Index (PSQI). We examined the relationships between SB-SQI, office workstation type (open-bench seating, cubicle, and private office), work-hours stress (standard deviation of heart rate variability), and after-work PA (relative duration of moderate-to-vigorous activity). Results: The sensor-derived poor-sleep ratio of the private office workers was higher than with other office workstation types (81% vs. 66.1%, p = 0.023). PSQI revealed a similar but insignificant trend with a lower effect-size. Among good-sleepers, open-bench seating workers had 22% (p = 0.018) less stress during work hours than others. A significant association between work-hours stress and after-work hours PA (r = 0.331, p = 0.000) was observed irrespective of office workstation type, with the highest PA level observed for open-bench seating workers. Conclusions: Office workstation type had a significant impact on work-hours stress, affecting PA after work hours, which influenced sleep quality. SB-SQI could be more sensitive than PSQI in determining the impact of office workstation types on sleep quality.

Background: Disruption of alternative splicing (AS) is frequently observed in cancer and it might represent an important signature for tumor progression and therapy. Exon skipping (ES) represents one of the most frequent AS events and in non-small cell lung cancer (NSCLC) MET exon 14 skipping was shown to be targetable. Methods: We constructed a neural network (NN) specifically designed to detect MET exon 14 skipping events using RNAseq data. Furthermore, for discovery purpose we also developed a sparsely connected autoencoder to identify uncharacterized MET isoforms. Results: The NN had 100% Met exon 14 skipping detection rate, when tested on a manually curated set of 690 TCGA bronchus and lung samples. When globally applied to 2605 TCGA samples, we observed that the majority of false positives was characterized by a blurry coverage of exon 14, but interesting they share a common coverage peak in the second intron and we speculate that this event could be the transcription signature of a LINE1-MET fusion. Conclusions: Taken together our results indicate that neural networks can be an effective tool to provide a quick classification of pathological transcription events and sparsely connected autoencoders could represent the basis for the development of an effective discovery tool.

Hearing impairment (HI) is a common sensory disorder that is defined as the partial or complete inability to detect sound in one or both ears. This diverse pathology is associated with a myriad of phenotypic expressions and/or syndromes. HI can be caused by various intrinsic, environmental and/or unknown factors. Some ontologies capture some relevant HI forms, phenotypes and syndromes, but there is no comprehensive knowledge portal which includes aspects specific to the HI disease state. This hampers inter-study comparability, integration and interoperability within and across disciplines. This work describes the HI Ontology (HIO) that was developed based on the Sickle Cell Disease Ontology (SCDO) model. This is a collaboratively developed resource built around the 'Hearing Impairment' concept by a group of experts in different aspects of HI and ontologies. HIO is the first comprehensive, standardized, hierarchical and logical representation of existing HI knowledge. HIO allows researchers and clinicians alike to readily access standardized HI-related knowledge in a single location and promote collaborations and HI information sharing, including epidemiological, socio-environmental, biomedical, genetic and phenotypic information. Furthermore, this ontology illustrates the adaptability of the SCDO framework for use in developing a disease-specific ontology.

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n=42) and European American (EA, n=33) women. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for calibration and quality assurance of inactivated SARS-COV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. Heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)- C-terminal domain (CTD) across all SARS-COV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprising of UV-inactivated SARS CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (Limit of Detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a twenty amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust ‘pan-variant’ antigen-based assays for viruses prone to high mutational rates.

Despite offering free-of-charge COVID-19 vaccines starting July 2021, Guatemala has one of the lowest vaccination rates in Latin America. During September 28, 2021 to April 11, 2022, we conducted a cross-sectional survey of community members adapting a CDC questionnaire to evaluate COVID-19 vaccine access and hesitancy. Of 233 participants ≥12 years, 127 (55%) received >1 dose of COVID-19 and 4 (2%) reported prior COVID-19 illness. Persons ≥12 years old unvaccinated (n=106) were more likely to be female (73% vs 41%, p<0.001) and homemakers (69% vs 24%, p<0.01) compared with vaccinated participants (n=127). Among those ≥18 years, the main reported motivation for vaccination among vaccinated participants was to protect the health of family/friends (101/117, 86%); 40 (55%) unvaccinated persons reported little/no confidence in public health institutions recommending COVID-19 vaccination. Community- and/or home-based vaccination programs, including vaccination of families through the workplace, may better reach female homemakers and reduce inequities and hesitancy.

Background: In this secondary analysis of the Supporting the Modification of Lifestyle In Lowered Emotional States (SMILES) randomised controlled trial, we investigated if the beneficial effects of a dietary intervention on clinical depression were driven, in part, by reducing the consumption of foods classified as ultra-processed.Methods: The SMILES trial enrolled 67 adults with major depressive disorder, randomly assigning them to either a 12-week modified Mediterranean dietary intervention or a social support control. Our analysis included 44 participants with non-missing dietary data and at least one valid Montgomery–Åsberg Depression Rating Scale (MADRS) assessment at 12 weeks of follow-up. The Nova food classification system was used to estimate the proportion of ultra-processed foods in the overall diet (percentage of grams) based on data from seven-day food diaries. We fitted linear regression models under blinded conditions to determine whether ultra-processed food intake-change from baseline to 12 weeks moderated the dietary intervention effects on depressive symptoms. We estimated mean differences in depressive symptoms along with ninety-five per cent confidence intervals (95%CIs).Results: For participants in the dietary intervention, there was an additional 2.5-point improvement in MADRS scores for each 10% reduction in the dietary share of ultra-processed foods compared to participants in the control group (between-group mean differences in depressive symptoms: −2.46, 95%CIs −4.71 to −0.20, p=0.039, η _p ² of 0.10).Conclusions: These preliminary findings suggest that the therapeutic benefit of a dietary intervention for depression may stem, at least in part, from reductions in the dietary share of ultra-processed foods.

Background: We previously found that QNBC tumors are more frequent in African Americans compared to TNBC tumors. To characterize this subtype further, we sought to determine the miRNA-mRNA profile in QNBC patients based on race. Methods: Both miRNA and mRNA expression data were analyzed from TCGA and validated using datasets from the METABRIC, TCGA proteomic, and survival analysis by KMPLOT. Results: miRNA-mRNAs which include FOXA1 and MYC (mir-17/20a targets); GATA3 and CCNG2 (mir-135b targets); CDKN2A, CDK6, and B7-H3 (mir-29c targets); and RUNX3, KLF5, IL1-β, and CTNNB1 (mir-375 targets) were correlated with basal-like and immune subtypes in QNBC patients and associated with a worse survival. Conclusion: Thus, QNBC tumors have an altered gene signature implicated in racial disparity and poor survival.

Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim of this study was to identify immune-related biomarkers that more effectively predict outcome of glioblastoma. Since heat shock protein 70 (Hsp70) and IL-2 are known to increase the expression of activatory NK cell receptors, recognizing aggressive human tumor cells that present Hsp70 on their cell surface, extracellular Hsp70 levels were determined in glioma patients together with activatory NK cell receptors. All gliomas are membrane Hsp70-positive (mHsp70+) and high grade gliomas more frequently show an overexpression of Hsp70 in the nucleus and cytosol. Significantly increased extracellular Hsp70 levels are detected predominantly in glioblastomas with large necrotic areas. Overall survival (OS) is more favorable in patients with low Hsp70 serum levels indicating that a high Hsp70 expression is associated with an unfavorable prognosis. Elevated frequencies of NK cells are associated with a more favorable outcome. Of caution, a glucocorticoid therapy reduces the prevalence of NK cells. In summary, elevated frequencies of Hsp70-reactive NK cells at diagnosis and lower Hsp70 levels predict a more favorable prognosis in glioblastoma patients.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

The aim of this retrospective study was to compare the clinical outcomes of treating isolated surgical neck fractures of the humerus using either the intramedullary nail or the MIROS (Minimally Invasive Reduction and Osteosynthesis System®) system. The study included 42 patients who underwent surgical treatment at the Polyclinic from January 2014 to June 2020. The results indicated that both treatments were effective; however, the MIROS system exhibited a higher complication rate. Intramedullary nailing was more reliable, thus recommended as the primary treatment method. This study underscores the importance of selecting the appropriate fixation technique to minimize complications and enhance patient outcomes.