A heterobifunctional reactive oxygen species (ROS)-responsive linker for directed drug assembly onto and delivery from a quantum dot (QD) nanoparticle carrier was synthesized and coupled to doxorubicin using EDC/sulfo-NHS coupling. The doxorubicin conjugate was characterized using ¹H NMR and LC-MS and subsequently reacted under conditions of ROS formation (Cu²⁺/H₂O₂) resulting in successful and rapid thioacetal oxidative cleavage which was monitored using ¹H NMR. The deprotected amine linker is amenable to peptide or protein conjugation prior to QD assembly or to direct conjugation to cognate reactive groups on ligands that cap the QD surface.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

D-type cyclins encode G1/S cell cycle checkpoint proteins, that play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterised by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarise and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

The Compact Midwave Imaging System (CMIS) is a wide field of view, multi-angle, multi-spectral pushframe imager that relies on the forward motion of the satellite to create a two-dimensional (2D) image swath. An airborne demonstration of CMIS was successfully completed in January-February 2021 on the NASA Langley Research Center Gulfstream III. The primary objective of the four-flight campaign was to demonstrate the capability of this unique instrument to perform stereo observations of clouds and other particulates (e.g. smoke) in the atmosphere. It is shown that the midwave infrared (MWIR) spectral bands of CMIS provide a unique 24/7 capability with high resolution for accurate stereo sensing. The instrument relies on new focal plane array (FPA) technology, which provides excellent sensitivity at much warmer detector temperatures than traditional technologies. This capability enabled a compact, low-cost design that can provide atmospheric motion vectors and cloud heights to support requirements for atmospheric winds in the 2017-2027 Earth Science Decadal Survey. Applications include day/night observations of the planetary boundary layer, severe weather, and wildfires. A comparison with current space-based earth science instruments demonstrates that the SWIR/MWIR multi-spectral capability of CMIS is competitive with larger, more expensive instrumentation. Imagery obtained over a controlled burn and operating nuclear power plant demonstrated the sensitivity of the instrument to temperature variations. The system relies on a mature stereoscopic imaging technique applied to the same scene from two independent platforms to unambiguously retrieve atmospheric motion vectors (AMVs) with accurate height assignment. This capability has been successfully applied to geostationary and low-earth orbit satellites to achieve excellent accuracy. When applied to a ground-point validation case, the accuracy for the CMIS aircraft observations was 20 m and 0.3 m/s for cloud heights and motion vectors, respectively. This result was confirmed by a detailed error analysis with analytical and covariance models. The results for CMIS cases with underflights of Aeolus, CALIPSO and Aqua provided a good validation of expected accuracies. The paper also showed the feasibility of accommodating CMIS on CubeSats to enable multiple instruments to be flown in a leader-follower mode.

This paper explores the Wilsonian renormalization group of probe-D-branes, focusing on the Dirac-Born-Infeld (DBI) action. The analysis involves deriving the constant of motion and formulating the Wilsonian renormalization group equation. The study extends to the infrared regime, considering both zero and non-zero temperatures. Additionally, thermodynamic aspects related to the functional form of the grand potential are discussed. The investigation provides insights into the renormalization of probe-D-branes and their thermodynamic properties.

Keywords: lactic acid; ceramide; folate; nicotinamide; Alzheimer’s disease

Like 18F-FDG, 99mTc-1-thio-D-glucose (99mTc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of 99mTc-TG. Twelve lym-phoma patients were injected with 729±102 MBq 99mTc-TG. Whole-body planar imaging was per-formed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. 99mTc-TG injections were well tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone mar-row, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. 99mTc-TG SPECT/CT re-vealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal le-sions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using 99mTc-TG. Potentially, 99mTc-TG SPECT can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.

Background: Previous study of sexual minorities has documented both instability in the sex of sex partners and incongruity among all three dimensions of sexual orientation (attraction, behavior and identification), but no attempt has been made to relate the two. How, if at all, does past change affect present incongruity? This study attempts, for the first time, to examine this question. Method: Using a representative probability sample of the British population (n = 15,162), the current dimensions of sexual orientation were compared across changes in sex partner type—opposite-sex only (O/Sex), same-sex only (S/Sex), or both opposite-sex and same-sex (B/Sex)— over three time periods—before 5 years ago (Time 1), 5 years to 1 year ago (Time 2), and the past year (Time 3)—for the nonheterosexual population. Differences and trends in population-weighted percentage frequencies stratified by sex were assessed by t-test or inspection of 95% confidence intervals. Results: Overall incongruity and instability were high: 74% of men and 85% of women did not report congruent lifetime sexual attraction, behavior and identification; of persons reporting any same-sex sex partners at Time 1, 82% reported a different partner type at Time 3. Most change (80% for women, 84% for men) involved a single partner type transition (transience) rather than multiple changes (fluidity) and movement toward increased heterosexual orientation (69%; 65% to O/Sex partners. From Time 1 to Time 3, 19% of persons with S/Sex partners moved to O/Sex partners; 0.1% of persons with O/Sex partners moved to S/Sex partners. Instability moderately reduced already high incongruity for the majority moving toward increased heterosexual orientation, but increased already low incongruity for the minority moving toward increased same-sex orientation. Among presently S/Sex partnered persons (comprising 12% of sexual minorities), incongruity was reported by 1.4% of persons with stable partnership history and 11% of persons with unstable partnership history (p=.0052). For all except presently S/Sex partnered persons (comprising 88% of sexual minorities), incongruity was reported by 97% of persons with stable partnership history and 86% of persons with unstable partnership history (p=.0000). Conclusion: For most sexual minority persons, partner type instability contributed to a modest reduction of high sexual minority orientation incongruity after moving toward increased heterosexual practice. Among current S/Sex partnered persons, however, instability strongly increased incongruity between identification and behavior or attraction. These results are consistent with minority stress theory but inconsistent with homosexual immutability, and counsel caution regarding legal restrictions on support for sexual minority persons moving toward increased heterosexual partnership.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

Recent satellite measurements of glacier mass balance show mountain glaciers all over the world had generally negative mass balances in the first decades of the 21st century. Mean summer temperatures all over the world rose from 1961-90 to 1991-2020, implying increasingly negative mass balances. We study archived annual balances for 38 Northern Hemisphere glaciers to assess changes within in the 19612020 period. We use a modified doublemass curve to visualize mass balance changes occurring around 1990. Mean balances 196190 were already small negative for many of the studied glaciers and became even more negative in 19912020 for glaciers in the Alps, at high latitudes and in western North America. The largest mass balance changes are for some glaciers in the Alps. We are unable to explain the lack of change in mean balance for one glacier in High Mountain Asia. We find complex changes for eight glaciers in Scandinavia, even including one glacier with positive balance. We explain these changes by visualizing deviations of winter and summer balances from their respective 1961-90 mean values. High winter balances in the 1990s for Scandinavia partly obscured the emerging trend of increasingly negative summer balances, which we expect to continue in the future.

We present a case of serious and progressive neuropathy shortly following administration of the herpes zoster subunit (HZ/su) vaccine. The progressive neuropathy occurred a week following the vaccination and progressed until discharge 16 days post admittance. Mild patient’s symptoms persist. The development of neuropathy following HZ/su is exceedingly rare, with an attributable risk of 3 cases per million vaccines administered. A black box warning was issued for this indication, although diagnosis and treatment were not confirmed for this patient. Reporting cases like this is crucial for a comprehensive understanding of vaccine risks and to characterize the underlying etiology of these serious adverse events.

This review aims at studying the phytochemistry and biological activities of some selected Apocynaceae plants. Eleven members of this family were reviewed for their phytochemistry and biological activities. Interestingly, the commonly isolated compounds reported from Mondia whitei (Hook.f.) Skeels, Secondatia floribunda A. DC, Carissa carandas, Tabernaemontana divaricate, Nerium oleander, Wrightia tinctoria, T. divaricate, Alstonia scholaris, Carrisa spinarum Linn, Thevetia peruviana and Caralluma lasiantha were triterpenoids, flavonoids, phytosterols, cardiac glycosides and lignans. All of them exhibited remarkable biological activities, mostly similar to each other. This review provides a detailed insight into the pharmacological activities of these selected members of this family.

Background: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), Gulf War Ill-ness (GWI) and control subjects had fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction Methods: Activated midbrain nuclei were inferred by re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI had greater activation during cognition than ME/CFS in left pedunculotegmental nucleus. Postexercise ME/CFS had greater activation than GWI for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI indicating reciprocal patterns of activation. Controls had no changes. Conclusions: Exercise caused opposite effects with increased activation in ME/CFS but decreased activation in GWI indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.

Correlated binary data in a 2x2 table has been analyzed from both the frequentist and Bayesian perspectives, but a fully Bayesian hierarchical model has not been proposed. This is a commonly used model for correlated proportions when considering, for example, a diagnostic test performance where negative subjects are tested a second time. We consider a new hierarchical Bayesian model for the parameters resulting from a 2x2 table with a structural zero. We investigate the performance of the hierarchical model via simulation. We then illustrate the usefulness of the model by showing how a set of historical studies can be used to build a predictive distribution for a new study that can be used as a prior distribution for both the rate ratio and marginal probability of a positive test. We then show how the prior based on historical 2x2 tables can be used to power a future study that accounts for pre-experimental uncertainty. High quality prior information can lead to better decision making by improving precision in estimation and by providing realistic numbers to power studies.

Carukia barnesi (Cb), Malo kingi (Mk) and Chironex fleckeri (Cf) are dangerous Australian box jellyfish species that provoke distinct and not well understood envenomation syndromes. Specifically, Cb and Mk are small, rare and able to induce a systemic syndrome of generalised muscle pain and catecholamine excess termed “Irukandji syndrome”; Cf has been widely regarded as one of the most venomous organisms in the animal kingdom causing severe sting site pain combined with potentially lethal cardiotoxicity. Building on past studies of major chirodropid and carybdeid species venoms, this study compared the utility of various cubozoan specific antibody reagents to better define the relationships between venom proteins from both exemplar Irukandji species (Cb and Mk) and the archetype C. fleckeri box jellyfish. With the aid of commercial ovine derived Cf-specific antivenom, mouse antibodies reactive to Cb and Mk and rabbit antibodies specific to two Cf toxins (CfTX-1 and 2), as well as human sera, the cross-reactivity of jellyfish species-specific polyclonal antibodies against these three cubozoan venoms was investigated. Immunoblot assays revealed distinc levels of immune recognition across the three species, indicating that Mk specific reagents may bind both Irukandji and Cf venoms. Irukandji venom appears to be antigenic with the exception of a few proteins in the range of 43/46 kDa maybe homologous to CfTX-1 and 2. The implications of such antibody binding for future antivenom development require further investigation.

Nine components (C1-C9) were isolated from chloroform fraction of fractionated methanol extracts of Vernonia amygdalina leaves (FMEVA) by column chromatography. All the components C1 to C9 were purified and screened for hypoglycaemic activities in type-2 diabetic rats. The most potent hypoglycaemic component was elucidated on the basis of extensive spectroscopic (1D-, 2D-NMR, GC-MS, FTIR) data analysis. The Component C5 was found to be the most potent hypoglycaemic in reducing blood glucose by 12.55 ± 3.55% at 4 h post-oral administration, when compared to the positive (18.07 ± 1.20%) and negative (-1.99 ± 0.43%) controls. The spectroscopic data analysis reveals that the isolated compound has a structure consistent with 11β,13-dihydrovernolide. The isolated compound is part of the hypoglycaemic components present in V. amygdalina leaves that is responsible for the anti-diabetic activities. Further research is needed in the development of this compound or its derivatives for pharmaceutical use.

Background/Objectives: Women's reproductive and overall well-being are intricately associated to vitamin D levels. In Morocco, vitamin D deficiency is a major issue for premenopausal women, yet little data exists on their dietary intake of this nutrient. This study explores vitamin D dietary intake, socio-demographic determinants, and its correlation with serum 25-hydroxyvitamin D [25(OH)D3] in premenopausal Moroccan women. Methods: A cross-sectional study was conducted with 355 women aged 18-49 in Meknes, Morocco, using validated questionnaires to assess dietary intake and sun exposure. Potential covariates such as physical activity and BMI were also assessed . Serum 25(OH)D was measured via chemiluminescence immunoassay. Chi-square tests and Spearman correlation were used to identify socio-demographic factors influencing vitamin D intake. Linear and multivariate regression analysis determined the main predictors of serum 25(OH)D levels. Results :The median (interquartile range) vitamin D dietary intake was 2.8 (2.7) µg/day , with less than 20% of women meeting the recommended 5 µg/day. Major dietary sources were fish (48%), dairy (24.3%), and meat (9.4%), with fortified foods contributing only for 7%. Lower intake was linked to younger age (p=0.004) and rural living (p=0.024). While no significant association was found between dietary intake and serum 25(OH)D ((β(SE): 0.155(0.094), p=0.340 ) , sun exposure positively predicted serum levels(β(SE): 0.343 (0.128), p=0.008) , and BMI negatively affected them (β(SE): -1.128 (0.337), p=0.001). Conclusions: Our findings highlight insufficient vitamin D intake among premenopausal Moroccan women, especially younger and rural women. Nutritional interventions are needed to address this deficiency, promoting better dietary habits, sun exposure, and healthy weight.

We develop and apply a systematic literature review methodology to identify and characterize the ways in which the peer-reviewed literature depicts how climate change adaptation is occurring in Australia. We reviewed the peer-reviewed, English-language literature between January 2005 and January 2018 for examples of documented adaptation actions. Our results challenge previous assumptions that adaptation action is not happening in Australia and describes adaptation processes that are underway. For the most part, actions can be described as preliminary or groundwork, with a particular focus on documenting stakeholder perspectives on climate change and adaptation, and modelling or scenario planning in the coastal zone, agriculture and health sectors. Where concrete adaptations are reported, they are usually in the agricultural sector and are most common in the Murray-Darling Basin, Australia’s food basket. The findings of the review advance our understanding of adaptation to climate change as a process and the need to consider different stages in the process when tracking adaptation.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

Bats have been identified as the natural hosts of several emerging zoonotic viruses, including paramyxoviruses, such as Hendra and Nipah viruses, that can cause fatal disease in humans. Recently, African fruit bats with populations that roost in or near urban areas have been shown to harbour a great diversity of paramyxoviruses, posing potential spillover risks to public health. Understanding the circulation of these viruses in their reservoir populations is essential to predict and prevent future emerging diseases. Here, we identify a high incidence of multiple paramyxoviruses in urine samples collected from a closed, captive colony of circa. 115 straw-coloured fruit bats (Eidolon helvum). The sequences detected have high nucleotide identities with those derived from free ranging African fruit bats and form phylogenetic clusters with the Henipavirus genus, Pararubulavirus genus and other unclassified paramyxoviruses. As this colony had been closed for 5 years prior to this study, these results indicate that within-host paramyxoviral persistence underlies the role of bats as reservoirs of these viruses.

Transient receptor potential vanilloid (TRPV) channels act as sensors of pain, temperature, and other external stimuli. We have recently shown that DPV576, an aqueous mixture of nanodiamond (ND) and nanoplatinum (NP), can modulate the activity of TRPV on human primary keratinocytes, suggesting their potential as a possible pain modulator [1]. CD4+ T lymphocytes also express TRPV channels, and we sought with special interest to examine the effect of DPV576 in modulating the functions of TRPV channel expression and secretion of cytokines on human CD4+ T lymphocytes. Human primary CD4+ T cells were activated with anti CD3/CD28 with and without DPV576 at 1:25 and 1:100 dilutions for 24 hours in vitro. TRPV Receptor expression (TRPV1 and TRPV4) on CD4+ T cells was examined by flow cytometry. The capacity of DPV576 to modulate the activity of TRPV1 agonist capsaicin in CD4+ T cells was also determined. Activation of CD4+ T cells was determined by production of cytokines TNF-α, IFN-γ, and IL-10 using specific ELISA kits. DPV576 treatment of CD4+ T cells that were activated with anti CD3/CD28, resulted in increased expression of TRPV1 channel but had no effect on TRPV4. This was accompanied by increased secretion of IFN-g and reduced expression of TRPV1 in capsaicin activated CD4+ T cells. In addition, DPV576 inhibited the capsaicin, induced the production of both IFN-g and TNF-α, and enhanced the secretion of IL-10. We conclude that short term exposure to DPV576 inhibits the activity of TRPV1 channels in CD4+ T lymphocytes, which may suggest its possible beneficial use for pain management.

Methane (CH4) is the second most significant contributor to climate change after carbon dioxide (CO2), accounting for approximately 20% of the contributions from all the well-mixed greenhouse gases. Understanding the spatiotemporal distributions, and the relevant long-term trends are crucial to identifying the sources, sinks, and impacts on climate. Hyperspectral thermal infrared (TIR) sounders, including the Atmospheric Infrared Sounder (AIRS), the Cross-track Infrared Sounder (CrIS), and the Infrared Atmospheric Sounding Interferometer (IASI), have been used to measure global CH4 concentrations since 2002. This study analyzed nearly twenty years of data from AIRS and CrIS and confirmed a significant increase in CH4 concentrations in the mid-upper troposphere (around 400 hPa) from 2003 to 2020, with a total increase of approximately 85 ppb, representing a +4.8% increase in 18 years. The rate of increase was derived using global satellite TIR measurements is consistent with in-situ measurements, indicating a steady increase starting in 2007 and became stronger in 2014. The study also compared CH4 concentrations derived from the AIRS and CrIS against ground-based measurements from NOAA Global Monitoring Laboratory (GML) and found phase shifts in the seasonal cycles in the middle to high latitudes in the northern hemisphere, which is attributed to the influence of stratospheric CH4 that varies at different latitudes. These findings provide insights into the global budget of atmospheric composition and the understanding of satellite measurement sensitivity of CH4.

Background and Objectives: Intramedullary spinal cord tumors (IMSCT) are rare entities. Especially, a location in the upper cervical spine as a highly eloquent region carries the risk of postoperative neurological deficits, such as tetraparesis or respiratory dysfunction. Evidence for respiratory dysfunction is scarce. The aim of this study was to describe the early and late postoperative clinical course of this highly eloquent tumours. Patients and Methods: This is a single-centre retrospective cohort study. We included 35 patients with IMSCT at levels of craniocervical junction to C4 who underwent surgical treatment between January 2008 and December 2022. The authors analysed the patients' preoperative status, tumour- and surgery-specific characteristics, and follow-up functional status. Results: The study cohort included 22 patients with grade II ependymoma (62.9%), 2 low-grade astrocytomas (5.7%), 2 glioblastomas (5.7%), 6 hemangioblastomas (17.1%), 2 metastases (5.7%), and 1 patient with partially intramedullary schwannoma (2.9%). Gross total resection was achieved in 76% of patients. Early dorsal column related symptoms and motor deterioration occurred in 64% and 44% of patients, respectively. At a follow-up of 3.27 ± 3.83 years, 43% and 33% of patients preserved postoperative sensory and motor deterioration, respectively. The median McCormick Scale grade was 2 in the preoperative and late postoperative periods, respectively (p=0.0897, α=0.05). Only two out of 35 patients (5.7%) developed new intermittent respiratory dysfunction, of whom two were transient. There were no surgery-related deaths. Conclusions: The surgery of IMSCT of the upper cervical spine could be performed without major procedure-related risk. Roughly a half of the patients develop new neurological deficit in the immediate postoperative period. However, most of the patients still maintain functional independence. The rate of respiratory insufficiency is low and is strongly influenced by the rapid neurological deterioration in high-grade tumours.

We conducted a study to determine if antenatally collected maternal urine cotinine (a me- 13 tabolite of nicotine) measurements can be used to assess the neonatal impact of nicotine exposure 14 during pregnancy. This was a prospective longitudinal cohort of mother-infant dyads. Only term 15 singleton pregnancies were included. The primary outcome measure was the correlation between 16 maternal urine cotinine and infant birth weight. We analysed data from 238 mother-neonates' dy- 17 ads. Urine cotinine was detected in 50.4 % (120/238) women from the whole cohort, but only 16% 18 (38/238) self-reported as smokers (chi-square 39.7, p<0.0001), and these women had significantly 19 smaller babies (p=0.010). There was a significant negative correlation between maternal urine co- 20 tinine and birth weight (Spearman's coefficient = -0.0226, p=0.013). Female babies born to women 21 with nicotine in the urine were significantly smaller (p= 0.001). The number of women exposed to 22 nicotine during late pregnancy (measured in urine) was markedly higher than self-reported and 23 National smoking percentages, suggesting an urgent need for improvement of medical record re- 24 porting on smoking habits to better assess neonatal outcomes.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

In this study, we performed a bibliographical review examining the scientific literature on “feeding in Anthozoa” theme for the period from 1890 to 2019, using scientific databases (Google Scholar) supplemented with additional literature. This study categorized published scientific papers on this topic by decade of publication, target taxa, variability of species studied in each order and main themes studied. As a result, 153 studies were found, and based on their content, it was observed that within Anthozoa, there has been a concentration of feeding studies on species in the orders Actiniaria (Hexacorallia), Scleractinia (Hexacorallia), and Alcyonacea (Octocorallia). This indicates that the other remaining orders of the group have been comparatively neglected with regards to their feeding aspects. Therefore, as data on feeding in some groups of Anthozoa are scarce, studies need to be carried out to fill the gaps that permeate this important benthic group, in order to better understand their ecology.

Ethanolic extracts of propolis collected from Apis mellifera hives have been shown to reduce Nosema ceranae infection in honey bee workers. This study aimed to determine the propolis concentration that optimizes the control of N. ceranae infection in honey bee workers. Newly emerged worker bees were individually fed 2 μL of 50% sucrose solution (w/v) containing 105 N. ceranae spores per bee, and treated with 0%, 25%, 50%, and 75% ethanolic extracted propolis in 50% sucrose solution (v/v). The treated bees were maintained in cages at 34 ± 2˚C and 55 ± 5% RH throughout the study. The number of dead bees was counted and removed from the cages daily for 30 days to generate survival curves. The number of N. ceranae spores per bee (infectivity) was quantified using a hemocytometer, and the number of infected bees per hundred bees (infection rate) was determined. The survival rates of N. ceranae infected bees fed 25%, 50%, and 75% propolis (NP1, NP2, NP3, respectively) were significantly higher than those of infected bees not fed propolis (NO). Furthermore, the infectivity and infection rates of NP2 and NP3 groups were significantly lower than those of the NO group. The infectivity and infection rates of the NP1 group were not different than those of the NO group. Our data suggest that 50% and 75% propolis extracts are appropriate concentrations for treating N. ceranae infection in honey bees. Ethanolic extracted propolis can be an alternative treatment for N. ceranae infection in Western honey bees.

Indigenous forests cover 24% of New Zealand and provide valuable ecosystem services. However, a national map of forest types, that is, physiognomic types, which would benefit conservation management, does not currently exist at an appropriate level of detail. While traditional forest classification approaches from remote sensing data are based on spectral information alone, the joint use of space-based optical imagery and structural information from synthetic aperture radar (SAR) and canopy metrics from air-borne Light Detection and Ranging (LiDAR) facilitates more detailed and accurate classifications of forest structure. We present a support vector machine (SVM) classification using data from ESA’s Sentinel-1 and 2 missions, ALOS PALSAR, and airborne LiDAR to produce a regional map of physiognomic types of indigenous forest in New Zealand. A five-fold cross-validation of ground data showed that the highest classification accuracy of 80.9% is achieved for bands 2, 3, 4, 5, 8, 11, and 12 from Sentinel-2, the ratio of bands VH and VV from Sentinel-1, HH from PALSAR, and mean canopy height and 97th percentile canopy height from LiDAR. The classification based on the optical bands alone was 73.1% accurate and the addition of structural metrics from SAR and LiDAR increased accuracy by 7.8%. The classification accuracy is sufficient for many management applications for indigenous forest in New Zealand, including biodiversity management, carbon inventory, pest control, ungulate management, and disease management. National application of the method will be possible in several years, once national LiDAR coverage is achieved, and a national canopy height model is available.

The synthesis of enantiomeric forms of D-amino acids can be achieved by a two-step "hydantoinase process" based on the sequential catalysis of substrates by specific enzymes, D-carbamoylase and D-hydantoinase. In addition to our previously studied D-hydantoinase, we describe here the structural features of D-carbamoylase from Pseudomonas, the encoded gene of which was chemically synthesized and cloned into Escherichia coli. A significant fraction of the overexpressed recombinant protein forms insoluble inclusion bodies, which are partially converted to a soluble state upon treatment with N-lauroylsarcosine or upon incubation of the cells at low temperatures. Analysis of the substrate specificity of the purified His-tag protein showed that D-carbamoylase exhibits the highest activity toward N-carbamoyl-D-alanine and N-carbamoyl-D-tryptophan. Molecular docking analysis revealed the location of the substrate binding site in the three-dimensional structure of D-carbamoylase. Molecular dynamics simulations showed that the binding pocket of the enzyme in complex with N-carbamoyl-D-tryptophan is stabilized within 100 ns. The free energy of binding indicated a possible role of residues Arg176 and Asn173 in the formation of hydrogen bonds between the enzyme and N-carbamoyl-D-tryptophan. The properties of the studied D-carbamoylase and D-hydantoinase support further development of a combined biotechnological process for the production of new drugs and peptide hormones.

The recent rise in ocean temperatures, accompanied by other environmental changes, has notably increased the occurrence and spread of diseases in Octocorallia, of which many species are integral to shallow tropical and subtropical coral reef ecosystems. This study focuses on the understanding of these diseases, which has been largely limited to symptomatic descriptions, with clear etiological factors identified in only a fraction of cases. A key example is the multifocal purple spots syndrome (MPSS) affecting the common Caribbean octocoral sea fan Gorgonia ventalina, linked to the gall-forming copepods of the genus Sphaerippe, a member of the widespread family Lamippidae. The specialized nature of these copepods as endoparasites in octocorals suggests the potential for the discovery of similar diseases across this host spectrum. Our investigation employed four molecular markers to study disease hotspots in Saint Eustatius, Curaçao, northwest and southwest Cuba, and Bonaire. This led to the discovery of a group of copepod species in these varied Caribbean locations. Importantly, these species are morphologically indistinguishable through traditional methods, challenging established taxonomic approaches. The observed diversity of symbionts, despite the host species' genetic uniformity, is likely due to variations in larval dispersal mechanisms. Our phylogenetic analyses confirmed that the Lamippidae copepods belong to the order Poecilostomatoida (Copepoda) and revealed their sister group relationship with the Anchimolgidae, Rhynchomolgidae, and Xarifiidae clades, known for their symbiotic relationships with scleractinian corals. These results add to our understanding of the evolutionary and ecological interactions of copepods and their hosts, and the diseases they cause, important data in a changing climate.

The Australian tropical montane cloud forest (TMCF) is home to approximately 18 percent of the nation’s total vascular plant species. Over the past century, human activity and industrial development have caused global climate changes, posing a severe and irreversible danger to the entire land-based ecosystem, and WTWHA is no exception. The current average annual temperature of WTWHA in FNQ is 24 °C. However, in the coming years (by 2030), the average annual temperature increase is estimated to be between 0.5 and 1.4 °C compared to the climate observed between 1986 and 2005. Looking further ahead to 2070, the anticipated temperature rise is projected to be between 1.0 and 3.2 °C, with the exact range depending on future emissions. We identified 84 plant species endemic to the WTWHA in FNQ, which are already experiencing climate change threats. Few of these plants are used in herbal medicines. This study comprehensively reviewed metabolomics studies conducted on these 84 plant species until now toward understanding their physiological and metabolomics responses to global climate change. This review also discusses: i) recent developments in plant metabolomics studies that can be applied to study and understand the interactions of wet tropical plants with climatic stress, ii) medicinal plants and isolated phytochemicals with structural diversity, and iii) reported biological activities of crude extracts and isolated compounds.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.

The application of smartphone-based color evaluation of passive sampling devices for gases has only been sparsely reported. The present review aims to compile available publications with respect to the configuration of the passive samplers, conditions of smartphone photographing, analytical procedure for color detection and quantification (including calibration processes), and their application to different target gases. The performance of the methods - whenever available - is presented regarding the analytical specifications selectivity, sensitivity, and limit of detection in comparison with other color evaluation methods of passive samplers. Practical aspects like requirements of instrumentation and ease of use will be outlined in view of the potential employment in education and citizen science projects. In one section of the review the inconsistent terminology of passive and diffusive sampling is discussed in order to clarify the distinction of information obtained from the uptake of the passive samplers between gas-phase concentration and the accumulated deposition flux of gaseous analytes. Colorimetric gas sensors are included in the review when applied in passive sampling configurations and evaluation is performed with smartphone-based color evaluation. Differences in the analytical procedures employed after the passive sampling step and prior to the detection of the colored compounds are also presented.

Gastrointestinal parasites (GIP) are diverse parasitic organisms known to have coevolved with bacterial populations inside the gut of mammalian hosts. These helminths produce small molecules, peptides and proteins to evade or fight their hosts' immune systems. Small molecules include polar compounds, amino acids, lipids and carbohydrates. Metabolomics is an emerging field of research recently applied to study helminth infections and host-parasite interactions. This review comprehensively discusses metabolomics studies of small molecules of GIP in animals, providing insights into the available tools and techniques, databases, and analytical software. Most metabolomics investigations employed LC-MS, MS or MS/MS, NMR, or a combination thereof. Recent advancements in metabolomics platforms, including artificial intelligence (AI)-assisted software tools and databases, have propelled helminth metabolomics forward, offering new avenues to explore host-parasite interactions, immunomodulation, and the intricacies of parasitism. As our understanding of helminth metabolomics continues to expand, it promises to unveil novel perspectives and enrich the knowledge of these complex host-parasite relationships.

This study checked whether vitamin D (Vit-D) supplementation improves the efficacy of resistance training (RT) in terms of increasing muscle strength and lean body mass (LBM) and influencing cardiorespiratory fitness (VO2max) in Vit-D insufficient middle-aged healthy men. Participants (n = 28) were quasi‐randomly assigned to one of the two groups, which, in a double‐blind manner, supplemented their diet daily with either Vit‐D (8000 IU; VD) or placebo (PLC) during participation in a 12‐week supervised RT program. During the intervention, serum Vit‐D concentrations increased 2.6‐fold (p < 0.001) in the VD group, while no changes occurred in the PLC group. Muscle strength gains (p < 0.001) as measured in seven exercises performed on RT equipment and increases (p < 0.001) in LBM were similar in the two groups. Total fat mass, percent total fat, and percent android fat decreased (p < 0.05) to a similar extent in both groups, but there was no change in VO2max in either group. In conclusion, in healthy Vit‐D insufficient middle-aged men engaged in resistance training, Vit‐D supplementation increases serum 25(OH)D levels but does not enhance gains in muscle strength and LBM or decreases in fat mass and fat percentage and does not affect cardiorespiratory fitness.

Ship detection from synthetic aperture radar (SAR) imagery is crucial for various fields in real-world applications. Numerous deep learning-based detectors have been investigated for SAR ship detection, which require a substantial amount of labeled data for training. However, SAR data annotation is time-consuming and demands specialized expertise, resulting in that deep learning-based SAR ship detectors struggle due to a lack of annotations. With limited labeled data, semi-supervised learning is a popular approach for boosting detection performance by excavating valuable information from unlabeled data. In this paper, a semi-supervised SAR ship detection network is proposed, termed as Multi-Teacher Dempster-Shafer Evidence Fusion Net-work (MTDSEFN). The MTDSEFN is an enhanced framework based on the basic teacher-student skeleton frame, comprising two branches: the Teacher Group (TG) and the Agency Teacher (AT). The TG utilizes multiple teachers to generate pseudo-labels for different augmentation versions of unlabeled samples, which are then refined to obtain high-quality pseudo-labels by using Dempster-Shafer (D-S) fusion. The AT not only serves to deliver weights of its own teacher to the TG at the end of each epoch, but also updates its own weights after each iteration, enabling the model to effectively learn rich information from unlabeled data. The combination of TG and AT guarantees both reliable pseudo-label generation and learning comprehensive diversity information from numerous unlabeled samples. Extensive experiments were performed on two public SAR ship datasets, and the results demonstrated the effectiveness and superiority of the proposed approach.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in &gt; 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged &lt;13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations; G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n=37, 67.2%) and comprised three G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 lineage). Both two G3 lineages have been recently detected in several countries. Our study is the first to document African children infection with G3 lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.

Previous studies in our lab show that that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (T_IBAT) in male DIO rats. What remains unclear is whether chronic hindbrain (4V) OT can impact body weight in female high fat diet-fed (HFD) rodents and whether this involves activation of BAT. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce body weight in female high fat diet-fed rats. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of T_IBAT and reduction of body weight in DIO rats. We first measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (0.5, 1, and 5 µg ≈ 0.5, 0.99, and 4.96 nmol) to stimulate T_IBAT in female HFD-fed rats. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) stimulated T_IBAT similarly between sham rats and denervated rats (P=NS). We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day ≈ 16.1 mg/day) or vehicle infusion to reduce body weight, adiposity and energy intake in female HFD-fed rats (N=7-8/group). Chronic 4V OT reduced body weight gain (sham: -18.0±4.9 g; denervation: -15.9±3.7 g) and adiposity (sham: -13.9±3.7 g; denervation: -13.6±2.4 g) relative to vehicle treatment (P<0.05) and these effects were similar between groups (P=NS). These effects were attributed, in part, to reduced energy intake evident during weeks 2 (P<0.05) and 3 (P<0.05). To test whether these results translate to other female rodent species, we also examined the effect of chronic 4V infusion of OT on body weight and adiposity in two strains of female HFD-fed mice. Similar to what we found in the HFD-fed rat model, we also found that chronic 4V OT (16 nmol/day) infusion resulted in reduced body weight gain, adiposity and energy intake in female DIO C57BL/6J and DBA/2J mice (P<0.05 vs vehicle). Together, these findings suggest that 1) sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and weight loss in female HFD-fed rats and 2) the effects of OT to elicit weight loss translate to other mouse models of diet-induced obesity.

Height assignment is an important problem for satellite measurements of Atmospheric Motion Vectors (AMVs) that are interpreted as winds by forecast and assimilation systems. Stereo methods assign heights to AMVs from the parallax observed between observations from different vantage points in orbit while tracking cloud or moisture features. In this paper, we fully develop the stereo method to jointly retrieve wind vectors with their geometric heights from geostationary satellite pairs. Synchronization of observations between observing systems is not required. NASA and NOAA stereo-winds codes have implemented this method and we have processed large datasets from GOES-16, -17, and Himawari-8. Our retrievals are validated against rawinsonde observations and demonstrate the potential to improve forecast skill. Stereo winds also offer an important mitigation for the loop heat pipe anomaly on GOES-17 during times when warm focal plane temperatures cause infra-red channels that are needed for operational height assignments to fail. We also examine several application areas, including deep convection in tropical cyclones, planetary boundary layer dynamics, and fire smoke plumes, where stereo methods provide insights into atmospheric processes. The stereo method is broadly applicable across the geostationary ring where systems offering similar Image Navigation and Registration (INR) performance as GOES-R are deployed.

Rice provides ~20% of human dietary energy and, for many people, a similar share of their protein. Rice cultivation, however, produces significant greenhouse gas (GHG) emissions, comparable to those from the aviation sector. The main GHG from rice production is methane, mostly a result of conventional rice cultivation (CRC) keeping rice fields continuously flooded during the crop cycle. There is extensive evidence that alternate wetting and drying (AWD) of rice fields substantially reduces methane emissions. AWD is one component of the System of Rice Intensification (SRI), an agroecological approach to the management of plants, water, soil and nutrients practiced by millions of farmers in both lowland irrigated rice and upland rainfed cultivation. Thirteen countries have included SRI in their Nationally Determined Contributions to GHG reduction or climate change mitigation. This article reviews 16 field studies of the net reduction in GHG emissions from the adoption of AWD, eight from the adoption of SRI, and two that compared SRI and AWD. Where available, the review includes data on yield and therefore on carbon dioxide-equivalent GHG emissions per kilogram of rice produced. The evidence indicates that AWD and SRI offer a similar and substantial reduction (~35–41%) in GHG emissions per hectare compared with conventional rice cultivation. However, SRI offers ~66% greater yield than CRC, and therefore greater reduction in emissions per kilogram of rice, ~54% more than AWD. The limited data directly comparing SRI and AWD support this finding. SRI also appears to have greater potential to sequester carbon in the soil. SRI lowers rice farmers’ costs of production, adds to their income and can make climate-friendly methods more attractive. Both AWD and SRI are greatly preferable to current conventional practices, but SRI offers opportunities to contribute to food security while directly addressing the drivers of climate change.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Antimicrobial resistance (AMR) represents a growing crisis in both human and veterinary medicine. We evaluated the use of two categories of antibiotic alternatives – heavy metals and essential oils – in beef cattle, and their effects on gram-negative and gram-positive bacteria. In this randomized controlled field trial, we measured the impact of supplemental zinc and menthol on antimicrobial resistance among commensal enteric bacteria of feeder cattle. Fecal suspensions were plated onto plain- and antibiotic-supplemented MacConkey and m-Enterococcus agar for quantification of total and antimicrobial-resistant Escherichia coli and Enterococcus spp., respectively. Temporal effects on overall E. coli growth were significant (P&lt; 0.05); however, there were no significant effects on antibiotic-supplemented agar. Zinc was associated with significant increases in growth on erythromycin-supplemented m-Enterococcus agar. Cattle fed zinc exhibited significantly higher macrolide resistance among fecal enterococci isolates.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Phosphorus (P) is an important and irreplaceable macronutrient. It is central to energy and information storage and exchange in living cell. P is an element with “broken geochemical cycle” since it lacks abundant volatile compounds capable of closing the P cycle. P fertilizers are critical for global food security, but the reserves of minable P are scarce and non-evenly distributed between countries of the world. Accordingly, the risks of global crisis due to limited access to P reserves is expected to be graver than those entailed by competition for fossil hydrocarbons. Paradoxically, despite the scarcity and value of P reserves, its usage is extremely inefficient: current waste rate reaches 80% giving rise to a plethora of unwanted consequences such as eutrophication leading to harmful algal blooms. Microalgal biotechnology comprise a promising solution to tackle this challenge. The proposed review briefly presents the relevant aspects of microalgal P metabolism such as cell P reserve composition and turnover, and the regulation of P uptake kinetics for maximization of P uptake efficiency with the focus on novel knowledge. Multifaceted role of polyPhosphates, the largest cell depot for P, is discussed with emphasis on the P toxicity mediated by short-chain polyPhosphates. Opportunities and hurdles of P bioremoval via P uptake from waste streams with microalgal cultures, either suspended or immobilized, is discussed along with the role of bacterial components of microalgal-bacterial consortia in these processes. Possible avenues of P-rich microalgal biomass such as biofertilizer production or extraction of valuable polyPhosphates and other bioproducts are considered. The review concludes with a comprehensive assessment of the current potential of microalgal biotechnology for ensuring the sustainable usage of phosphorus.

Untargeted metabolomics is a powerful tool for measuring and understanding complex biological chemistries. However, employment, bioinformatics and downstream analysis of mass spectrometry (MS) data can be daunting for inexperienced users. Numerous open-source and free-to-use data processing and analysis tools exist for various untargeted MS approaches, including liquid chro-matography (LC), but choosing the ‘correct’ pipeline isn’t straight-forward. This tutorial, in con-junction with a user-friendly online guide presents a workflow for connecting these tools to process, analyse and annotate various untargeted MS datasets. The workflow is intended to guide explor-atory analysis in order to inform decision-making regarding costly and time-consuming down-stream targeted MS approaches. We provide practical advice concerning experimental design, organisation of data and downstream analysis, and offer details on sharing and storing valuable MS data for posterity. The workflow is editable and modular, allowing flexibility for updated/ changing methodologies and increased clarity and detail as user participation becomes more common. Hence, the authors welcome contributions and improvements to the workflow via the online repository. We believe that this workflow will streamline and condense complex mass-spectrometry approaches into easier, more manageable, analyses thereby generating opportunities for researchers previously discouraged by inaccessible and overly complicated software.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

This is a single tertiary center in southwest Romania, population-based, study. We retrospectively compared data obtained in two periods: January 2008 - December 2013 and January 2018 - De-cember 2023, respectively. The global incidence of transposition of great arteries (TGA) - the ter-minated cases added to the ones resulting in live-born pregnancies, remained almost constant. The live-born incidence of TGA decreased (0.34% to 0.013%). The prenatal detection rate increased slightly (71.42% to 87.5%). The median gestational age at the diagnosis decreased, from 29.3 ges-tational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The proportion of terminated pregnancies significantly increased (14.28% to 75%, p = 0.019).

Weathering and erosion transport minerals and organics toward the sea or lake bottoms over geologic time. The finest solids are deposited in lower, less turbulent areas, such as lake bottoms and continental shelves. They sometimes stack up to thicknesses of kilometers, and begin compacting. These sediment sections are called shales, and as initially deposited in water, shales can have porosities up to 50-80{\%} water, As they are buried, many alteration products from oil to slate are produced due to overburden and temperature increasess, making them important to study. A preceeding paper \cite{1} showed that pressure solution is the primary mechanism for porosity reduction, with possible mechanical compaction at shallow depths. Without naming the mineral(s) involved, it postulated that the greater the product of the water and pore interfaces, the faster the reaction would proceed. This term is $ \varphi^{4m/3}(1-\varphi)^{4n/3}$ , where $\varphi$ is porosity and m and n are numbers close to unity. The large exponents, {\em 4/3}, recognize that the reaction occurs at the molecular scale at which the surfaces are rough. A second term, $\exp^{(-E/RT)}$ , indicates that the reaction is impeded by a quantum energy barrier, E, with diminished impeding power as increased available thermal energy, represented by the absolute temperature, T, becomes available at greater depths in the Earth. These two factors combine to allow porosity $\varphi$ to reduce with time, or equivalently for the fraction of solids, $(1-\varphi)$, to increase with time,$\left. \frac{\partial(ln(1-\varphi) ) }{\partial t } \right |_{\sigma} = (\varphi )^{4m/3}( 1-\varphi )^{4n/3}Ae^{-E/(RT)}$. { \em Here it is shown that this equation can cover quantitatively any actual deposition rates which may have been experienced by the six sections studied, the actual deposition rates being unknown for these cases. Hence a time-depth depositional history for any new shale section, known in detail, would allow determination of the parameters m, n, E and a lumped proportionality constant A. This was accomplished by showing that, for a wide range of depositional rates, r, the range of E for any of the studied sections is small compared to laboratory measurements of quartz solution\cite{2}, 24+-15kJ/mol. Results were obtained over this range of r's using the previously determined m and n, and porosity and temperature profiles. The presently existing porosity profiles necessarily incorporate any overpressure or underpressure conditions that may have existed in the past or currently, as the net difference between overburden and pore pressure is a primary driving force for pressure solution. $SiO_2$ usually comprises 20-50{\%} of shales. In conclusion, pressure solution of quartz can account for vertical compaction of shales quantitatively in the studied examples. Separately, a quasi-eqivalent method for discussing reduced porosities in Macron 2 versus Macron 1 as increased vertical stress, rather than additional horizontal stress, is illustrated. Experiments are suggested to clarify the pressure solution mechanism. The role of horizontal forces is discussed. From a global point of view, shale compaction by pressure solution is a quantified step in the cycling of continental rocks, beginning with rifting.

Multiple sclerosis is an autoimmune disorder where both T cells and B cells are implicated in pathology. However, it remains unclear how these two distinct populations cooperate to drive disease. There is ample evidence from studies in both MS patients and mouse models that Th17, B cells, and follicular T helper (TFH) cells contribute to disease. This review article describes the literature that identifies mechanisms by which Th17, TFH, and B cells cooperatively drive disease activity in MS and EAE. The curation of this literature has identified that CNS-infiltrating TFH cells act with TH17 cell to contribute to an inflammatory B cell response in neuroinflammation. This demonstrates that TFH cells and their products are promising targets for therapies in MS.

Calcium sulfate (CS) materials containing terbium ions at 0, 1.0, or 2.0 mol.% were obtained by mechanochemical synthesis. According to X-ray diffraction data, the powder materials are characterized by the presence of a CaSO4×0.5H2O phase, while Tb3+ is incorporated into the lattice at ≤1.0 mol.%. Specific surface area enlarged from 2.1 to 22.5 m2/g as crystallite size decreased from 68 to 31 nm and the Tb3+ concentration increased up to 1.0 mol.%. Thermal analysis showed that terbium slightly raises the temperature of CaSO4×2H2O-to-CaSO4 transition. The presence of Tb3+ did not affect the solubility of the CS cements. Furthermore, after 7 days of soaking of the materials in a simulated body fluid, a calcium phosphate layer formed corresponding to a hydroxyapatite phase, in contrast to the pure cements. Luminescent properties were studied by excitation at 276 nm. The recorded emission peaks of the CS materials indicated that the luminescence of the samples is green and blue, with the most intense luminescence observed for samples containing 1.0 mol.% Tb3+. The developed materials can find applications in medicine as bioimplants for the regeneration and restoration of bone tissue with a possibility of noninvasive monitoring of the bone restoration process.

The expression of the oncogene zinc-finger protein 217 (ZNF217) has been reported to play a central role in cancer development, resistance, and recurrence. Therefore, targeting ZNF217 has been proposed as a possible strategy to fight cancer, making necessary to discover novel com-pounds. The present work aims to characterize the chemopreventive properties of cucurbitacin D , a compound with a broad range of anticancer effectsin relation to the ZNF217 expression. Different cucurbitacins were isolated from the Vietnamese plant Elaeocarpus hainanensis. The purified compounds were tested on nucleophosmin-mutated acute myeloid leukemia and other hematology cancer to study their effects on viability, apoptosis, cell cycle and on the expression of ZNF217. Cucurbitacin D reduced the number of acute myeloid leukemia cells by increasing apoptosis and blocking cell cycle progression. It also significantly decreased ZNF217 expression but only in the OCI-AML3 Nucleophosmin-mutated cell line, but not in other hematologic cancers. The reduction in ZNF217 expression contributed significantly to the blocking of cell cycle progression but not to apoptosis as established by the silencing of the same gene. The obtained results suggest Cucurbitacin D as a promising molecule to target the mutated Nu-cleophosmin or its pathway in acute myeloid leukemia cells, although further studies are needed for in depth investigatiion of its specificity.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of Vitamin D, there has been a progressive advancement in analytical technologies for its determination, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of Vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the determination of Vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. Additionally, given the important interrelations between Vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Neuropathic pain (NeP) is a complex and debilitating condition that impacts millions of people globally. Although various treatment options exist, their effectiveness is often limited, and they can be accompanied by significant side effects. In recent years, there has been increasing interest in targeting the N-methyl-D-aspartate receptor (NMDAR) as a potential therapeutic approach to alleviate different types of neuropathic pain. This narrative review aims to provide a comprehensive examination of NMDAR antagonists, specifically ketamine, memantine, methadone, amantadine, carbamazepine, valproic acid, phenytoin, dextromethorphan, riluzole, and levorphanol, in the management of NeP. By analyzing and summarizing current preclinical and clinical studies, this review seeks to evaluate the efficacy of these pharmacologic agents in providing adequate relief for NeP.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

Human papillomavirus (HPV) can potentially compromise both unassisted conception and success rates with assisted reproductive technology (ART). We aimed to evaluate the rates of HPV vaccination among women presenting for fertility care. This was a prospective study analyzing a self-reported intake form completed by all new patients presenting to a fertility clinic. The primary outcome was HPV vaccination status. Among the 523 new patients included in this study 172 (32.9%) were fully vaccinated, 237 (45.3%) were unvaccinated, and 95 (18.2%) patients didn’t respond. There was a significant age difference between fully vaccinated patients (33.1 years) compared to unvaccinated patients (37.4 years) p&lt;0.001 and a significant difference in gravidity between fully vaccinated patients (average 0.65) and unvaccinated patients (average 1.11) p=0.0005. No significant association was found between HPV vaccination status and history of abnormal Pap smears or relationship status (single vs. married). Less than half of patients presenting to our fertility center were vaccinated against HPV, despite being eligible to receive the vaccine. Younger patients with lower gravidity were more likely to be vaccinated against HPV than older patients with higher gravidity. Reproductive Endocrinologists have the opportunity to recommend HPV vaccination for eligible patients presenting for fertility care.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

This paper presents the Aether Physics Model (APM), a novel theoretical framework that offers a unified description of the fundamental forces and weak interaction. The APM proposes a quantum Aether composed of discrete units, recognizes two distinct charge manifestations, and treats all charges as distributed. Using dimensional analysis and simple equations, the APM derives force equations that unify gravity, electromagnetism, and the strong forces and the weak interaction. The model makes specific predictions about force strengths, maximum mass density, and fine structure constants for protons and neutrons. These predictions align with existing observations and offer new avenues for experimental testing. The APM addresses the limitations of the Standard Model while providing a more intuitive explanation for phenomena like the quantum Hall effect and Casimir effect. If validated, the APM could revolutionize our understanding of space, matter, and fundamental forces.

The Aether Physics Model (APM) presents a radical reinterpretation of fundamental physics, offering potential solutions to long-standing problems in Quantum Mechanics and General Relativity. This paper explores the core concepts and equations of the APM, demonstrating how they provide a unified framework for understanding the nature of space, time, matter, and fundamental forces. We examine the implications of the APM's quantized Aether structure, the role of the Singularity and Gforce, and the reinterpretation of fundamental constants and forces. The model's predictions regarding dark matter, neutron content in stable matter, and the unification of forces are discussed, along with potential experimental tests. Additionally, we introduce the loxodrome concept and toroidal particle topology as central elements in explaining fundamental particles and forces. While speculative, the APM offers a thought-provoking alternative to standard physics models and warrants further investigation.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

Manned missions to Mars and other deep space exploration targets are expected to take place in the next 20 years. These missions will involve prolonged crew exposure to the unique space environment, increasing the risk that astronauts will experience additional physical and psychological health conditions beyond those that would be expected through normal aging on Earth. Thus, there is an acute need to develop therapeutic solutions that can withstand the harsh space environment, while maintaining astronaut health and maximizing crew capabilities to foster successful exploration-class missions. This review covers the nuanced and interdisciplinary challenge that is providing safe and effective pharmaceuticals for future deep space missions. First, the limitations of current pharmaceutical solutions are discussed; the impacts of the space environment on human health and chemical compound stability are covered, along with an evaluation of astronaut medication use on similar missions. Second, potential pharmaceutical solutions and concepts are presented for consideration. Future research should prioritize these and other potential innovations to ensure that our space programs are well equipped to maximize crew safety as astronauts explore deep space objectives.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

OPMDs (Oral Potentially Malignant Disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of a range of diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also reveals a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD, and investigate their potential association and ramifications for clinical management of OPMDs.

In the present work we revise and extend the Characteristic Crystallographic Element (CCE) norm, an algorithm used to simultaneously detect radial and orientational similarity of computer-generated structures with respect to specific reference crystals and local symmetries. Based on the identification of point group symmetry elements, the CCE descriptor is able to gauge local structure with high precision and finely distinguish between competing morphologies. As test cases we use computer-generated monomeric and polymer systems of spherical particles interacting with the hard-sphere and square-well attractive potentials. We demonstrate that the CCE norm is able to detect and differentiate, between others, among: hexagonal close packed (HCP), face centered cubic (FCC), hexagonal (HEX) and body centered cubic (BCC) crystals as well as non-crystallographic fivefold (FIV) local symmetry in bulk 3-D systems; triangular (TRI), square (SQU) and honeycomb (HON) crystals, as well as pentagonal (PEN) local symmetry in thin films of one-layer thickness (2-D systems). The descriptor is general and can be applied to identify the symmetry elements of any point group for arbitrary atomic or particulate system in two or three dimensions, in the bulk or under confinement.

Viral variant analysis is a bedrock of the disease surveillance. When combined with temporospatial analysis variant analysis can further the knowledge of disease spread in a study area. This paper suggests a method to perform the analysis in an operational setting which will allow for real-time surveillance of viral variants and allow local public health professionals to rapidly respond to changes in the evolution of the disease. This method includes three main subprocesses: preprocessing, analysis, and rendering. This method can be performed across multiple software platforms. A use case is given in which it was found that this method helped a hospital system understand the spread of SARS-CoV-2 in Northeast, Ohio.

A micro decision-making utility model under uncertainty is presented as a complementary foundation for macro coronavirus models. The micro model consists of two functions, a risk averse utility function depending on wellness and a wellness random output which is a function of the input variable called “treatment” consisting of such elements as social distance, washing hands, wearing a face mask, and others. The decision maker selects a level of treatment that maximizes her/his expected utility, given the probabilities of the respective outputs. The focus is on how changes in a person’s psychological attitude towards the macro determined (announced) probabilities affects the optimum results of the model. Such changes create a micro-macro dynamic interaction which is briefly outlined. A short discussion of the model’s behavioral implications for health policy is also given.

Abstract: The marketing of Sugar-Sweetened Beverages (SSBs) within grocers is an obesogenic factor that negatively impacts children’s nutritional behavior, specifically regarding people from racial and ethnic minority groups. We aimed to develop and employ a methodology that more precisely assesses the availability, price, and promotion of SSBs to young immigrant children within independently owned grocery stores. A case comparison design was used to explore the differences in the grocery store landscape of SSB marketing by conducting an enhanced Nutrition Environment Measures Survey-SSB (NEMS-SSB) within 30 grocery stores in the Hispanic and Latino enclaves in Southwest Detroit, in the Arab and Chaldean enclaves in North-central Detroit, and in Warren, Hamtramck, and Dearborn, in comparison with 48 grocers in Metro Detroit. Organic, plant-based, and unsweetened toddler and infant beverages, as well as questions about marketing, were added to the original NEMS-S to capture the promotion tactics used in marketing SSBs. NEMS-SSB scores revealed in the immigrant enclaves there was a significantly higher availability of SSBs in grocery stores (−2.38), and they had lower prices than those in the comparison group (−0.52). Availability of unsweetened and organic beverages was zero in 97% of all participating grocery stores. Signage featuring cartoon characters was the most frequent in-store SSB marketing tactic. Widespread SSB marketing towards toddlers within the grocery stores in immigrant enclaves could be linked with the higher childhood obesity prevalence among this population. Our findings can assist local and national organizations in developing and implementing healthy eating interventions. This study can be repeated in other states to provide comparable results.

Experimental systems to simulate future elevated CO2 conditions in the field often have large, rapid fluctuations in CO2. To examine possible impacts of such fluctuations on photosynthesis, intact leaves of field grown plants of five species were exposed to two-minute cycles of CO2 between 400 and 800 mol mol-1 lasting a total of 10 minutes, with photosynthesis, stomatal conductance and PSII fluorescence measured at the end of each half-cycle, and also 10 minutes after the end of the cycling. Prior to the cyclic CO2 treatments, steady-state responses of leaf gas exchange and fluorescence to CO2 were determined. In four of the five species, in which stomatal conductance decreased with increasing CO2, the cyclic CO2 treatments reduced stomatal conductance. In those species, both photosynthesis and the photochemical efficiency of PSII were reduced at limiting internal CO2 levels, but not at saturating CO2. In the fifth species, there was no change in stomatal conductance with CO2, and no change in either photosynthesis or PSII efficiency at any CO2 level with CO2 cycling. It is concluded that in many, but not all, species fluctuations in CO2 may reduce photosynthesis at low CO2 partly by decreasing the photochemical efficiency of photosystem II, as well as by decreasing stomatal conductance.

There is an overarching need to find alternative treatment options for malaria and this quest is more pressing in current times due to the morbidity and mortality data arising from most endemic countries and partially owing to the fact that the SARS-Cov-2 pandemic has diverted much public health attention. Additionally, the therapeutic options available for malaria has been severely threatened with the emergence of resistance to almost all existing drugs by the human malaria parasite. The Artemisinin Combination Therapies (ACTs) which hitherto have been the mainstay for malaria have encountered resistance in South East Asia, a notorious ground zero for the emergence of antimalarial drug resistance. This review analyses few key druggable targets of the parasite and the potential to leverage strategic inhibitors to mitigate the scourge of malaria by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Furthermore, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage such findings for antimalarial drug production.

The risk classification of barrier lake is the key to conducting emergency treatment in a scientific manner. Such difficulties are faced as short time for risk evaluation, complex evaluation indicators, difficulty in obtaining information quickly and quantifying index weights. Based on this, this paper constructs a quantitative risk classification model for barrier lakes based on D-AHP. On the basis of studies on nearly 100 cases of barrier lakes, an 8-factor evaluation index system and quantitative classification are proposed. The methods of rapid calculation of reservoir capacity curve of barrier lake and intelligent identification of particles on the surface of barrier body were developed, which realized the rapid acquisition of 8-factor evaluation index information in emergency environment. The D-AHP method dealt with inconsistent weight assignment to evaluation factors by experts, which helped achieve weight quantification of 8 factors. The risk assessment on15 barrier lakes such as Tangjiashan barrier lake show that the conclusion drawn with risk classification method proposed in this paper is basically consistent with that of the traditional table-lookup method. However, the table-lookup method ignores cumulative loss’s impacts on the risk level of barrier lakes, and considers the extremely severe loss of barrier lakes as a sufficient condition for the evaluation level to be grade I, and thus a deviation in the evaluation. The risk classification method proposed in this paper is more reasonable and reliable.

Recent in vivo assays of the responses of Rubisco to temperature in C₃ plants have revealed substantial diversity. Three cultivars of soybean (Glycine max L. Merr.), Holt, Fiskeby V, and Spencer, were grown in indoor chambers at 15, 20, and 25 ^oC. Leaf photosynthesis was measured over the range of 15 to 30 ^oC, deliberately avoiding higher temperatures which may cause deactivation of Rubisco, in order to test for differences in temperature responses of photosynthesis, and to investigate in vivo Rubisco kinetic characteristics responsible for any differences observed. The three cultivars differed in the optimum temperature for photosynthesis (from 15 to 30 ^oC) at 400 µmol mol^-1 external CO₂ concentration when grown at 15 ^oC, and in the shapes of the response curves when grown at 25 ^oC. The apparent activation energy of the maximum carboxylation rate of Rubisco differed substantially between cultivars at all growth temperatures, as well as changing with growth temperature in two of the cultivars. The activation energy ranged from 58 to 84 kJ mol-1, compared with the value of 64 kJ mol^-1 used in many photosynthesis models. Much less variation in temperature responses occurred in photosynthesis measured at nearly saturating CO₂ levels, suggesting more diversity in Rubisco than in electron transport thermal properties among these soybean cultivars.

One of the major areas of research in a business setting has been the effect of the transformational leadership style on workplace engagement. Much debate has taken place on the definitions of both constructs but in recent years, general agreement appears to have been reached on the Multi-Factor Leadership Questionnaire (MLQ) (Avolio and Bass, 2004) as the measure of transformational leadership, and on workplace engagement measured by the Utrecht Work Engagement Scale (UWES) (Schaufeli et al, 2006). However, in the education setting, there is much less agreement on the definition of transformational leadership. Furthermore, there is less of a focus on workplace engagement than in the business field even though available evidence suggests that workplace engagement worldwide is in crisis. This study sought to address both the lack of agreement on the transformational leadership definition and the lack of focus on workplace engagement in educational research by means of a meta-analysis. The meta-analysis resulted in a significant pooled effect size although due recognition is given to the endogeneity problem in causal studies. The endogeneity issue together with the results of the meta-analysis are discussed with a view to furthering educational leadership research.

Abstract: This study reviewed aspects of the biology of two members of the glucosinolate family, namely sinigrin and glucoraphanin and their anti-tumour and anti-microbial properties. Sinigrin and glucoraphanin are converted by the β-sulphoglucosidase myrosinase or the gut microbiota into their bioactive forms, allyl isothiocyanate (AITC) and sulphoraphanin (SFN) which constitute part of a sophisticated defence system plants developed over several hundred million years of evolution to protect them from parasitic attack from aphids, ticks, bacteria or nematodes. Delivery of these components from consumption of cruciferous vegetables rich in the glucosinolates also delivers many other members of the glucosinolate family so the dietary AITCs and SFN do not act in isolation. In-vitro experiments with purified AITC and SFN have demonstrated their therapeutic utility as antimicrobials against a range of clinically important bacteria and fungi. AITC and SFN are as potent as Vancomycin in the treatment of bacteria listed by the World Health Organisation as antibiotic-resistant "priority pathogens" and also act as anti- cancer agents through the induction of phase II antioxidant enzymes which inactivate potential carcinogens. Glucosinolates may be useful in the treatment of biofilms formed on medical implants and catheters by problematic pathogenic bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus and are potent antimicrobials against a range of clinically important bacteria and fungi. The glucosinolates have also been applied in the prevention of bacterial and fungal spoilage of food products in advanced atmospheric packaging technology which improves the shelf-life of these products.

This study develops a hybrid machine learning (ML) algorithm integrated with IoT technology to improve the accuracy and efficiency of soil monitoring and tomato crop disease prediction in Anakapalle, a south Indian station. An IoT device collected one-minute and critical soil parameters—humidity, temperature, pH values, nitrogen (N), phosphorus (P), and potassium (K)—essential for assessing soil health and optimizing crop growth. Kendall's correlations were computed to rank these parameters for utilization in hybrid ML techniques. Various ML algorithms including K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Decision Tree (DT), Random Forest (RF), and Logistic Regression (LR) were evaluated. A novel hybrid algorithm, 'Bayesian Optimization with KNN', was introduced to combine multiple ML techniques and enhance predictive performance. The hybrid algorithm demonstrated superior results with 95% accuracy, precision, and recall, and an F1 score of 94%, while individual ML algorithms achieved varying results: KNN (80% accuracy), SVM (82%), DT (77%), RF (80%), and LR (81%) with differing precision, recall, and F1 scores. This hybrid ML approach proved highly effective in predicting tomato crop diseases in natural environments, underscoring the synergistic benefits of IoT and advanced ML techniques in optimizing agricultural practices.

Whereas bisexuality, as it existed in modernity, has been described as a ‘floating signifier', one that was problematically conflated with gender and intersex bodies, the articulation of bisexuality is now experiencing a discursive resurgence in spaces and platforms online. Through a deliberately disparate comparison between Virginia Woolf’s modernist writing and the discussions of bisexuality on the video-sharing social networking service TikTok, this essay presents a reflective reassessment of how far bisexual representation in the popular imagination has progressed and by extension, evaluate extant limitations. To realize these ambitions, I compare the reception of sexology (the new science of sexuality) in ‘high’ modernist literature with a post-modern demographic whose bisexuality is articulated in the 2020s online via TikTok’s towards what I would demarcate as a post-queer theory user base. This essay is not intended as an overview of the advancements made in psychoanalytic institutions about bisexuality nor does it set out to comment on the refinement of bisexuality’s aestheticization through time. Instead, it uses these two temporally specific moments in the cultural zeitgeist to compare and contrast how differently two different demographics articulate bisexuality, both as a written mode in modernism and as a visual apparatus online. This is less a critique of bi-erasure, but an interrogation of why and how bisexual representation, as an aestheticized subjectivity that compromises romantic, spiritual, and erotic desires for bodies of all genders, continues to be problematically restrictive.

Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.

Vitamin D and iron deficiencies are the most prevalent micronutrient deficiencies among women of reproductive age (WRA) in Morocco. Recent studies suggest that Vitamin D deficiency (VDD) may reduce iron bioavailability necessary for erythropoiesis, potentially leading to iron deficiency (ID) and anemia. This study investigates the association between vitamin D status, iron levels, and anemia risk among Moroccan WRA aged 18-49 years. A cross-sectional study was conducted with 463 participants. Serum levels of 25(OH)D, blood count parameters, iron, ferritin, C-reactive protein, and creatinine were measured. Lifestyle factors, including dietary intake, sun exposure, and physical activity, were evaluated using validated questionnaires, and anthropometric data were collected. Linear and logistic regression models assessed the relationships between variables, while Receiver Operating Characteristic (ROC) curve analysis evaluated the predictive accuracy of VDD for ID and anemia. VDD (25(OH)D &lt; 20 ng/ml) was significantly associated with lower levels of hemoglobin, hematocrit, red blood cells, and ferritin (all p &lt; 0.01), suggesting a role of vitamin D in erythropoiesis and iron storage. Multivariate logistic regression showed that VDD increased the risk of anemia (OR: 7.17, 95% CI: 3.19-19.28, p &lt; 0.001), ID (OR: 2.20, 95% CI: 1.32-3.77, p = 0.007), and IDA (OR: 4.10, 95% CI: 1.73-12.08, p = 0.004). Dietary iron intake was inadequate among all participants, with minimal protective effect against anemia and ID (β(SE): -0.08(0.03), p = 0.030 and β(SE): -0.05(0.02), p=0.037 respectively). ROC analysis demonstrated moderate discriminative power for VDD in diagnosing IDA and anemia (AUC: 0.643 and 0.603) but reduced accuracy for ID (AUC: 0.575). This study identifies VDD as a significant risk factor for impaired iron status and anemia among Moroccan WRA, underscoring the need for targeted nutritional interventions and further research to explore effective prevention strategies.

The most recent National Research Council Nutrient Requirements for Sheep and Goats was published in 2007, one of the most consequential nutrient requirement recommendations for sheep and goats in the world. It is pertinent to continue the refinement and discussion of nutrient utilization and requirements for the purposes of enhancing the efficiency of production systems, maximizing resource economy, and minimizing the carbon footprint, among others. Progress has been made in the estimation of energy and protein requirements in sheep and goats, mainly utilizing empirical feeding experimentation, comparative slaughter technique and minimum endogenous loss method. In sheep, newer estimates of energy and protein requirements for maintenance and growth and partial efficiencies had been reported since 2007. There were suggestions that energy and protein requirements could have been affected by breed, wool growth, gender and size; with these reported values being similar or lower than the recommended values in international feeding systems such as NRC, ARC, INRA and AFRC. In goats, energy and protein requirements for growing goats were reported to be either higher or lower than the established recommendations, depending upon meat or dairy breeds. Effect of gender on energy requirement appeared to be related to the stage of growth or degree of maturity. Newer data also suggested that the guidelines of the major feeding systems for the entire growth phase may not be adequate for non-pregnant and non-lactating pubertal females. In multiparous pregnant goats, energy and protein requirements for maintenance did not appear to be affected by days of pregnancy, but efficiencies of metabolizable energy and metabolizable protein utilization for pregnancy were. There were suggestions that that metabolizable protein synthesis in the rumen can be predicted from energy intake using combined equations that encompass both sheep and goats, but more data on goats were called for to account for specific differences in nutrition. In addition to sulfur, there has been progress made on the estimation of maintenance and growth requirements of calcium, phosphorus, potassium and magnesium in goats, with suggestions on the consideration of gender and breed differences. Species, level of Intake, genotype, mature size, age, gender, body composition, use of tissue energy, activity, season, and acclimatization continue to be important considerations for the estimation of nutrient requirements in sheep and goats, with emerging factors such as climate change, heat stress, parasitism and secondary plant compounds. Model equations and partial efficiencies used by NRC to predict energy and protein requirements for maintenance, growth, lactation, and fiber have been highlighted and discussed for the purpose of a more focus discussion and refinement for the future. Potential and limitation of both traditional and emerging methodologies in determining the nutrient requirements in sheep and goats were discussed. To justify the research investment, emerging methodologies such as nutrigenomics will have to be linked more directly to the improvement of production efficiency via more precise prediction of nutrient requirement.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

Background: Delis-Kaplan Executive Function System (D-KEFS) is a neuropsychological tool used in clinical practice to measure executive function in clinical and non-clinical populations, in individuals aged 8-89 years, and consists of nine subtests that can be administered either as a single system or separately. Aims: In the present study, were established norms for the Verbal Fluency Test as well as the Design Fluency Test of the D-KEFS in a Greek population aged 20 to 49 years, since there is no previous study conducted in Greece for these age clusters. Methods: The study sample consisted of 100 healthy adults (44.4% male and 55.6% female), aged 20 to 49 years (M=32.81 SD=11.04) with education from 12 to 18 years (M=14.73, SD= .91). First, Spearman and Pearson tests explored the associations of gender, age and education with D-KEFS subtests’ performance. Afterwards, we calculated normative data using raw scores and transformed to percentile scores. Results: The present study is the first attempt to calculate norms for the two fluency subtests of the D-KEFS in Greek adult population stratified by age and educational level. Conclusion: Future research will promote the use of D-KEFS, in order to introduce a widely used tool which measures all basic executive functions subtypes for Greek adult population. Given that the majority of neuropsychological tools are adapted for older adult population, the current study aims at filling the gap in neuropsychological assessment of young adults as well as those who have co existing neurological or psychiatric disorders.

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

Background: We previously developed a refined, tumor selective adenovirus, Ad5NULL-A20, har-boring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6 positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 hours post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6 selective manner, whilst cell killing me-diated by oncolytic Ad5NULL-A20 was αvβ6 selective. Biodistribution analysis following intrave-nous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor: liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20 based virotherapies efficiently target αvβ6 integrin positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic ap-plications, enabling tumor selective overexpression of virally encoded therapeutic transgenes.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic VSL#3 at improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and VSL#3 treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n=64) was treated with rifaximin (seven days per month for three months) followed by VSL#3, and group B (n=60) was treated with a placebo. At the beginning of the study and after three months of treatment, all patients completed NIH-CPSI and IBS-SSS questionnaires to score the severity of their urogenital and gastrointestinal symptoms, and we measured seminal plasma levels of IL-6 and IL-10 using ELISA. We defined patients who improved following the treatment as those with a ≥6-point reduction in their NIH-CPSI score or ≥50-point reduction in their IBS-SSS score. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI and IBS-SSS scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs 4.4 pg/mL) relative to baseline, whereas levels of IL-6 and Il-10 did not change in the placebo group. The co-occurrence of two clinical phenotypes (IBS-D plus IIIa prostatitis) result in increased intestinal inflammation and altered immune activation, both of which can be balanced by treatment with rifaximin and VSL#3.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

Valles Marineris (VM), the most prominent example of a Martian Valley Network, has been extensively studied for over 50 years, yet no detailed examination of the principal azimuths of the system exists. To address this, two methods are presented to precisely calculate the principal azimuths, a Bezier Spline analysis, and a GIS technique. The medial axis of the main canyon of VM was determined analytically from cubic polynomial splines fitted to 93 coordinate points along both north and south edges of the canyon. These splines were optimized, and medial axis points were calculated through numerical techniques that ensured orthogonality between the tangents of each spline and their connecting normal lines. 1,000 Medial Axis points were extracted, and various regression models constructed, including fitting to sinusoidal and cubic polynomial curves, achieving accuracies with R² values of 0.98 and 0.99, respectively. Principal azimuths were obtained using the sinusoidal equation with the slope of the tangent at any point x simply determined by the derivative of the curve’s equation. This analytic approach was cross-validated by a GIS method (using QGIS software), where a vector medial axis was obtained which produced principal azimuths that agreed with values from the analytic study with a correlation coefficient of 1.00, and a p value of 6.43e-65. The findings suggest that a deterministic process plays a significant role in the structural geometry of VM, highlighting its potential importance in the canyon’s formation.

We have now identified two thermodynamically distinct types (A and B) of energetic processes naturally occurring on Earth. Type A energy processes such as the classical heat engines, apparently well follow the second law of thermodynamics; Type B energy processes, such as the newly discovered thermotrophic function that isothermally utilizes environmental heat energy to do useful work in driving ATP synthesis, which follows the first law of thermodynamics (conservation of mass and energy) but does not have to be constrained by the second law, owing to their special asymmetric functions. Several Type-B energy processes such as asymmetric-function-gated isothermal electricity and epicatalysis have been created through human efforts. The innovative efforts on Type-B processes to enable isothermally utilizing endless environmental heat energy could help to liberate all peoples from their dependence on fossil fuel energy, thus helping to reduce greenhouse gas CO2 emissions and control climate change towards a sustainable future for the humanity on Earth.

Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRM), able to recognise pathogen- or dan-ger-associated molecular patterns (PAMP, DAMP) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self-cells, and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at C-terminus). Pulmonary sur-factant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air-liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells, and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeo-stasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term “cancer” includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumourigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy.

Blackcurrant leaf chlorosis associated virus (BCLCaV) was detected recently by next-generation sequencing (NGS) and proposed as a new and distinct species in the genus Idaeovirus. Genomic components of BCLCaV that were detected and confirmed include: 1) RNA-1 that is monocistronic and encodes the replicase complex; 2) a bicistronic RNA-2 that encodes a movement protein (MP) and the coat protein (CP) of the virus, with open reading frames (ORF) that overlap by a single adenine (A) nucleotide (nt) representing the third position of an opal stop codon of the MP ORF2a and the first position of the start codon of the CP ORF2b; 3) a subgenomic form of RNA-2 (RNA-3) that contains ORF2b; and 4) a concatenated form of RNA-2 that consists of a complementary and inverted RNA-3 conjoined to the full-length RNA-2. Analysis of NGS-derived paired-end reads revealed the existence of bridge reads encompassing the 3’-terminus and 5’-terminus of RNA-2 or RNA-3 of BCLCaV. The full RNA-2 or RNA-3 could be amplified using outward facing or abutting primers; also RNA-2/RNA-3 could be detected even after three consecutive RNase R enzyme treatments with denaturation at 95 ^oC preceding each digestion. Evidence was obtained indicating that there are circular forms of BCLCaV RNA-2 and RNA-3.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

This paper examines hybrid threats to maritime transportation systems, and their governance re-sponses; focusing on the congested Straits of Malacca and Singapore (SOMS) as an illustrative case study. The methodology combines secondary sources with primary data from 42 expert in-terviews, a 30-respondent survey, and two maritime security roundtables. Key findings were that ships’ critical systems are increasingly interconnected, yet aging IT infrastructure and minimal cybersecurity awareness among crews heighten risks. Meanwhile, regional terrorist groups have previously targeted shipping and shown considerable skill in exploiting online tools, aligning with broader calls for jihadist violence. Further, opportunistic piracy persists in the SOMS with the po-tential to disrupt shipping. Experts confirmed maritime cybersecurity lags other critical infra-structure sectors and needs updated governance. Initial International Maritime Organization (IMO) guidelines lack specificity but revisions and updated IMO guidance are in process, while Port state implementation of maritime cybersecurity standards varies. Crucially, information sharing remains inadequate, even as recorded attacks increase. Findings underscore that although major hybrid incidents have not occurred, simulations and threat actors’ capabilities demonstrate potential for catastrophic collisions or cascading disruption in congested waterways. Mitigating factors like redundancy and crew training are deficient currently. Some alignment between SOMS states on maritime security cooperation exists, but not cyber threats specifically. Key recommen-dations include an anonymous cyber-attack reporting system, reinforced training and shipboard systems, and consolidated regional frameworks. Until these priorities are addressed, the analysis concludes that hybrid vulnerabilities in this vital global chokepoint remain a serious concern.