Age is an essential trait for understanding the ecology and management of wildlife. A conventional method of estimating age in wild animals is counting annuli formed in the cementum of teeth. This method has been used in bears despite some disadvantages, such as high invasiveness and the requirement for experienced observers. In this study, we established a novel age estimation method based on DNA methylation levels using blood collected from 49 brown bears of known ages living in both captivity and the wild. We performed bisulfite pyrosequencing and obtained methylation levels at 39 cytosine-phosphate-guanine (CpG) sites adjacent to 12 genes. The methylation levels of CpGs adjacent to four genes showed a significant correlation with age. The best model was based on DNA methylation levels at just four CpG sites adjacent to a single gene, SLC12A5, and it had high accuracy with a mean absolute error of 1.3 years and median absolute error of 1.0 year after leave-one-out cross-validation. This model represents the first epigenetic method of age estimation in brown bears, which provides benefits over tooth-based methods, including high accuracy, less invasiveness, and a simple procedure. Our model has the potential for application to other bear species, which will greatly improve ecological research, conservation, and management.

Background: Immunomodulatory peptides are capable of stimulating or suppressing the immune system. Hence, deregulation of them can be considered as an immunotherapy approach. These peptides may have dual behavior in response to different infections. For instance, an antimicrobial peptide may act as an anticancer, tumor marker or even cause cancer progression. Methods: In this study, we used single-cell RNA sequencing analysis to investigate the deregulation of immunomodulatory peptides in malignant versus normal human breast epithelial cells. We validated the obtained results in chromatin accessibility level. Furthermore, we used a drug repositioning approach to change the expression of these peptides based on their role in cancer biology. Results: As a result, ten immunomodulatory peptides were upregulated in breast cancer versus normal. Chromatin was more accessible for these peptides in cancer cell lines versus normal. Among these ten peptides, five of them were tumor drivers (i.e., BST2, GAPDH, S100A8, S100A9 and HMGB1), three of them were anticancer (i.e., H2AFJ, SCGB2A1 and HMGN2), S100A7 had dual behavior in different cancers and ZG16B was a tumor marker. Using the LINCS L1000 database, we proposed a list of drugs that can deregulate the candidate peptides according to their role in the progression of malignancy. Conclusions: In conclusion, immunomodulatory peptides can be considered as drug targets based on their role in cancer biology.

Schistosoma mansoni is an intestinal parasite with one β-class carbonic anhydrase, SmaBCA. We report the sequence enhancing, production, catalytic activity, and inhibition results of the recombinant SmaBCA. It showed significant catalytic activity on CO 2 hydration in vitro with k cat 1.38 x 10 5 s -1 and k cat/K m 2.33 x 10 7 M -1 s -1. Several sulfonamide inhibitors, from which many are clinically used, showed submicromolar or nanomolar inhibitory effects on SmaBCA. The most efficient inhibitor with a K I of 43.8 nM was 4-(2-amino-pyrimidine-4-yl)-benzenesulfonamide. Other effective inhibitors with K Is in the range of 79.4 nM-95.9 nM were benzolamide, brinzolamide, topiramate, dorzolamide, saccharin, epacadostat, celecoxib, and famotidine. The other tested compounds showed at least micromolar range inhibition against SmaBCA. Our results introduce SmaBCA as a novel target for drug development against schistosomiasis, a highly prevalent parasitic disease.

Clinical Letter to the EditorFood-dependent exercise-induced anaphylaxis due to potato snacks involving recurring psychogenic abdominal painAkiko Ikedaa, Atsushi Inagakia, Yuki Nishikawaa, Mariko Shimizua, Chiharu Kawaguchia, Nayu Satob,c, Masashi Nakamurab,c, Tomofumi Kawabec, Kayoko Matsunagaba Department of Pediatrics, Yamato-Takada Municipal Hospital, Nara, Japanb Department of Integrative Medical Science for Allergic Disease, Fujita Health University School of Medicine, Aichi, Japanc General Research and Development Institute, Hoyu Co., Ltd., Aichi, JapanRunning title: FDEIA from potato snacks

A global decline in seagrass populations has led to renewed calls for their conservation as important providers of biogenic and foraging habitat, shoreline stabilisation, and carbon storage. Eelgrass (Zostera marina) occupies the largest geographic range among seagrass species spanning a commensurately broad spectrum of environmental conditions. However, relatively little is known about their fine-scale genetic structure and broad-scale genomic signatures of environmental adaptation, and in Canada, eelgrass is considered a single phylogroup despite occurring across three oceans. We used a pooled whole-genome re-sequencing approach to characterise population structure, gene flow, and adaptation of 23 eelgrass populations ranging from the Northeast United States, to Atlantic, subarctic, and Pacific Canada. We identified over 500,000 SNPs, which when mapped to a chromosome-level genome assembly revealed six broad clades of eelgrass across the study area, with pairwise FST ranging from 0 among neighbouring populations to 0.54 between Pacific and Atlantic coasts. Genetic diversity was highest in the Pacific and lowest in the Arctic, consistent with colonisation of the Arctic and Atlantic oceans from the Pacific. Using redundancy analyses and two climate change projection scenarios, we found that subarctic populations are more vulnerable to climate change through genomic offset predictions. Conservation planning in Canada should ensure that representative populations from each identified clade are included within a national network so that latent genetic diversity is protected, and gene flow is maintained. Northern populations, in particular, may require stronger protective measures given their susceptibility to change climate.

Background: nosocomial infection (NIs) is a major challenge in healthcare facilities and has been associated with prolonged hospital stay as well as increased morbidity and mortality. Aims: This research aimed to estimate the impact of acute decompensation (AD) consequences on the successive risk of nosocomial infections (NIs) and the go after outcome. Methods: A total of 250 hospitalized cirrhotic patients with decompensation were included in the study. Different decompensation events and after-effects in patients with or without NIs were compared. The logistic regression and Cox proportional hazards models were designed for NIs development and mortality at 28 days, respectively. Results: During hospitalization, 22.4 % of patients developed NIs. Remarkably, a higher percentage of patients with NIs had jaundice (42.9% vs. 26.8 %; p= 0.06 at admission compared to patients without NIs, whilst a lower percentage had gastrointestinal hemorrhage (14.3 vs. 33.5%; p=0.017+). Multivariate analysis revealed that jaundice was independently linked with the development of NIs (OR, 0.474; 95% CI: 0.24–0.92). The 28-day mortality rates of patients with NIs were significantly higher than those without NIs (21.4 vs. 9%; p = 0.014). According to the Cox proportional hazards model, jaundice stayed an independent risk factor for 28-day death (HR,8.38; 95% CI: 3.58–19.62). Conclusion: Different decompensation events have different impact on the incidence of Nosocomial infections. Jaundice is independently associated with occurrence of NIs and increased 28-day mortality. Therefore, prophylaxis measures are recommended to benefit this specific subsection of patients. Keywords Decompensation, nosocomial infections, jaundice, mortality, hospitalization

Internet of Things (IOT) related and IOT enabled education and research are becoming more prevalent in today’s academic environment. One of the challenges faced by educators and researchers is the availability of resources to support lab based, hands on learning and research projects. Existing resources are often highly customized, balkanized, and difficult to manage. For new technology areas such as IOT, these environments rarely provide opportunities for resource sharing and interdisciplinary collaboration. In this paper we describe the development of a multi-tenant, IOT centric platform, the Environmental Sensing Data Network (ESDN) meant to support plug and play sensor deployment and the tools necessary for data management. The platform turns the University campus into an open platform that can be used to easily set up IOT based labs for education, research, campus infrastructure management and community applications innovation. The paper covers the development of a sensor augmentation module facilitating easy deployment and management. The operational tools and services integration are also described. We believe the platform is an important step in facilitating distance and in person education and research. ESDN is rapidly expanding beyond the multi-site University campus supporting a growing number of research and community projects.

In the last two decades, an increasing number of bacterial species have been recognized that are able to generate a phenotypically diverse population that shares an identical genotype. This ability is dependent on a complex genetic regulatory network that includes cellular and environmental signals, as well as stochastic elements. Among Bacilli, a broadly distributed family of Rap (Response-regulator aspartyl phosphate) phosphatases is known to modulate the function of the main phenotypic heterogeneity regulators by controlling their phosphorylation. Even more, their related extracellular Phr (Phosphatase regulator) peptides function as quorum sensing signals, creating a cell-cell communication network that regulates the phenotypic development of the entire population. In this review, we examine the role that the Rap phosphatases and their Phr peptides play in the regulation of B. subtilis phenotypic differentiation, and in other members of the Bacillus genus. We also highlight the contribution of these regulatory elements to the fitness of bacterial cells and mobile genetic elements, e.g. prophages and conjugative vectors.

Alveolar bone exostoses (ABE) are benign localized convex outgrowths of buccal or lingual bone from the cortical plate, often known as buttress bone development. Our review and case series shows ABE following orthodontic treatment. If self-remission fails after orthodontic forces are removed, we have shown surgical methods to correct ABE

Several approaches can correct pseudo Class III anterior crossbite. 2x4 appliance, compressed open coil springs, Class III elastics, etc. All cause either soft tissue lacerations, smile line flattening or upper incisor overproclination.This paper describes a novel method to tip lower incisors into a normal overjet without compromising the upper dentition

Foot and ankle TB is rarest form of skeletal TB. It's symptoms may present slowly over an extended period of time, making a diagnosis difficult. For the best outcome and to reduce the risk of deformity diagnosis must be early. The treatment is 12 months rifampin-based regimen for drug-susceptible TB.

Studying Arctic ice formation stays in the focus of research groups over the past decades in the context of ice cover changes, thermal budget and climate agenda in general. Nevertheless, the phenomenon’s underlying mechanisms are still not completely understood and described. The main reason for the lack in understanding is the limited experimental access to the field data, thus there is a need to build competent analogies between the natural (ocean water – ice) and laboratory (binary alloy) conditions of the experiment as a step of data preparation for the verification of the mathematical model. In the current paper the existing qualitative models describing the process of melting and crystallization were expanded and the experimental method was developed copying the layering of the natural ocean water – ice mixture. The experimental set-up for studying the solidification within the intermediate zone was designed for Al-Cu alloys and the corresponding experimental data was used for the development of a binary phase-field model for solidification considering moving boundaries. The model includes the description of the free energy of both phases and their respective diffusion coefficients. It allows modeling of the eutectic alloys and potentially corresponding natural ocean water — ice mixture at a mesoscopic spatial level by including the concentration-driven phase transition. The novel results will help the quantitative understanding of solidification phenomena and are highly-evaluated from interdisciplinary point of view, including glaciology and geosciences, ultimately significant for the understanding the global climate change landscape.

Pakistan is one of the 36 water-stressed countries, with less than 1000 cubic per person annual water availability. Factors like global warming, urbanization, and irrigation for agribusiness have come into play in skyrocketing the need for water globally. As a low-middle income country, inhabitants of Pakistan are actively moving toward resolving the water crisis through rainwater harvesting during the monsoon period. Though the practice is simple, feasible, and cost-effective, there are certain health risks associated with it. Due to its virological and microbial quality, rainwater is highly contraindicated for potable use without proper treatment. Pathogens like Campylobacter jejuni, Salmonella spp., Giardia lamblia, hepatitis A virus, rotaviruses, etc, and fecal matter of animals like birds, mammals, and reptiles, contaminate the roof harvested rainwater (RHRW) and result in diseases such as Human enteritis, Acute diarrheal disease, Giardiasis, among many others. Apart from this, the sporadic multi-demics of dengue, malaria, and cholera being directly or indirectly related to the monsoon period impose a burden on Pakistan’s public health sector and improper Rooftop Rainwater Harvesting (RTRWH) adds to the stress. It is now imperative that doctors and public health officials join hands to counsel the public on individual and national levels to contain the recurring outbreaks of these diseases associated with the monsoon period. Procedures of RHRW treatment such as ultra-membrane filtration, UV treatment, safe roofing material, and first-flush diversion devices should be strategically promoted through awareness campaigns. Our article discusses the limitations for potable use of RHRW in this era of multi-demic and suggests strategies to retrieve favorable outcomes to cater to the water scarcity through RTRWH in the state effectively.

Interactions between invaders and resource availability may explain variation in their success or management efficacy. For widespread invaders, regional variation in plant response to nutrients can reflect phenotypic plasticity of the invader, genetic structure of invading populations, or a combination of the two. The wetland weed Alternanthera philoxeroides (alligatorweed) is established throughout the southeastern USA and California, and has high genetic diversity despite primarily spreading clonally. Despite its history in the USA, the role of genetic variation for invasion and management success is only now being uncovered. To better understand how nutrients and genotype may influence A. philoxeroides invasion, we measured the response of plants from 26 A. philoxeroides populations (three cp haplotypes) to combinations of nitrogen (4 or 200 mg/L N) and phosphorus (0.4 or 40 mg/L P). We measured productivity (biomass accumulation and allocation), plant architecture (stem diameter and thickness, branching intensity) and foliar traits (toughness, dry matter content, percent N, percent P). A short-term developmental assay was also conducted by feeding a subset of plants from the nutrient experiment to the biological control agent Agasicles hygrophila, to determine whether increased availability of N or P to its host influenced agent performance, as has been previously suggested. A. philoxeroides haplotype Ap1 was more plastic than other haplotypes in response to nutrient amendments, producing more than double the biomass from low to high N and 50-68% higher shoot:root ratio than other haplotypes in the high N treatment. A. philoxeroides haplotypes differed in 7 of 10 variables in response to increased N. We found no differences in short-term A. hygrophila development between haplotypes but mass was 23% greater in high than low N treatments. This study is the first to explore the interplay between nutrient availability, genetic variation, and phenotypic plasticity in invasive characteristics of the global invader, A. philoxeroides.

The objective of this work is to investigate the Iridium L-band downlink burst signal in terms of the cross-ambiguity characterization for single burst and multicarrier multi-burst mode, to demonstrate its suitability and capability as Signal of OPportunity (SoOP) for navigation. The Iridium bursts are collected and examined by demodulating without any prior knowledge for frame verification. Then, the ambiguity function (AF) for the two modes is investigated and deduced to assess the waveform properties with resolution and sidelobes in both the Doppler and delay domains. It has been found that, the simplex burst with maximum length of 20.32ms presents 40μs delay resolution and 49Hz Doppler resolution, and its AF yields a peak to interference floor ratio of 26.64dB, which are the best capability for the single burst mode. The multichannel multi-burst mode produces a significant improvement for the time delay resolution even if the AF profile degradation should be accepted. Issues relating to the AF property improvement also are identified during this study.

The field of food allergy has seen tremendous change over the past 5-10 years with seminal studies redefining our approach to prevention and management and novel testing modalities in the horizon. Early introduction of allergenic foods is now recommended, challenging the previous paradigm of restrictive avoidance. The management of food allergy has shifted from a passive avoidance approach to active interventions that aim to provide protection from accidental exposures, decrease allergic reaction severity and improve the quality of life of food-allergic patients and their families. Additionally, novel diagnostic tools are making their way into the clinical practice with the goal to reduce the need for food challenges and assist physicians in the -- often complex -- diagnostic process. With all the new developments and available choices for diagnosis, prevention and therapy, shared decision-making has become a key part of the medical consultation, enabling patients to make the right choice for them, based on their values and preferences. Communication with patients has also become more complex over time, as patients are seeking advice online and through social media, but the information found online may be outdated, incorrect, or lacking in context. The role of the allergist has evolved to embrace all the above exciting developments and provide patients with the optimal care that fits their needs. In this review, we discuss recent developments, as well as the evolution of the field of food allergy in the next decade.

Abstract Objective: To evaluate the results of the excision and chemotherapy treatment methods for ALHs located on the arytenoids. Study design: retrospective study. Methods: Twenty-six ALH patients in 29 different cases were enrolled in the study. Some patients were treated more than once. Twenty-nine cases of ALHs treated with either chemotherapy or excision were studied to assess the efficacy of both treatments. Results: All the patients in the ALH excision group were cured, and the ALHs did not recur. The mean lumen constriction score for the chemotherapy group was 2.95. The score for the ALH excision group was higher than that for the chemotherapy group. Conclusion: Both chemotherapy and excision are safe and effective treatments for ALHs located on the arytenoids. On the condition that the ALH is well exposed and can be completely removed, ALH excision surgery is a better method to treat ALHs located on the arytenoids.

Key points:  Diagnosis of AIFRS should be alert in the immunocompromised patient presenting with new-onset, rapidly progressive sinusitis with facial-cranio-orbital spread.  Extended debridement should be considered on a case-by-case basis.  Antifungal agent contributed greatly to the outcome of AIFRS.  Prognosis mostly up to the balance of underlying disease and fungal invasion, more emphasizes should be focused on comprehensive treatment.  AIFRS with facial-cranio-orbital involved often had a disastrous end.

Introduction: Vaccine hesitancy has historically played a large role in the low rate of the human papillomavirus (HPV) vaccine coverage in the United States and has further surfaced to the forefront of public discourse since the start of the COVID-19 pandemic. This study aims to determine how HPV vaccination attitudes and trends among primary care physicians and patients have changed since the COVID-19 pandemic. Design: Physicians and patients (aged 9-45) participated in a voluntary survey regarding HPV vaccination. In patients under 18 years of age, the survey was completed by the patient’s parent or guardian. Results: Of the 27 healthcare providers surveyed, 22.2% agreed that there has been an increase in misinformation about the HPV vaccine since the COVID-19 pandemic and 7.4% of providers believed that patients were less willing to discuss or receive the HPV vaccine. A majority of patients surveyed (87.7%) were aware of the HPV vaccine but only about a third of those patients had received all three doses of the vaccine (28.1%). Conclusion: Recent trends in receiving the HPV vaccine may be associated with the polarizing climate during the COVID-19 pandemic. Understanding how trends in vaccine hesitancy have changed since the pandemic will allow further and more targeted efforts to increase HPV vaccine uptake.

A document by Hamid Mottaghi Golshan. Click on the document to view its contents.

We present a 3D map of magnetic field orientation on the surface of the Local Bubble.  This map is the first of its kind to fully chart magnetic fields over an observed superbubble.  Recent work mapping the 3D shape and dynamics of the Local Bubble has revealed that the formation of all young stars within 200 pc of the Sun was triggered by the Bubble's rapid expansion.  The exact mechanics of this expansion, and the role that magnetic fields in the surrounding interstellar medium have played in regulating its evolution, is not yet clear.  By combining detailed models of the Bubble’s geometry (derived from 3D dust mapping) with the assumption that magnetic field vectors are tangent to the Bubble’s surface, we are able to infer the 3D magnetic field orientation from Planck plane-of-the-sky dust polarization orientations.  We analyze the relationship between the Bubble’s inferred magnetic field and background starlight polarimetry observations, and discuss how magnetic fields may have affected the dynamics of the Local Bubble and other nearby structures in the ISM.

Magnetic resonance imaging (MRI) studies have demonstrated differences in the subcortical structure of schizophrenia patients compared to controls; nonetheless, it is not clear whether these changes are reason for or the result of schizophrenia (SZ). We aimed to investigate whether the basal ganglia volume was different in medication- naïve first episode schizophrenia patients. Seventy-one drug-naïve patients with first-episode psychosis (FEP) who applied to outpatient clinics and were diagnosed according to DSM-5 as well as 47 healthy controls (HC) were included in the study (n=118, 64 males, 54 females). T1-weighted images were acquired on a 1.5 T scanner (Magnetom SP, Siemens), and the basal ganglia volume was measured using the VolBrain software. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) by an experienced psychiatrist. The volumes of right (R) and left (L) striatum, R- and L-caudate (CAU), and R- and L- Substantia nigra (SN) were found to be higher in FEP patients compared to the HC. The volume of L-putamen was higher, while that of the L- Globus pallidus (GP) and L-nucleus accumbens (NAcc) was smaller in FEP patients compared to HC. No significant correlation was found between volume measurements and PANSS scores. R-CAU, L-CAU, R-Striatum, L-Striatum, L-Putamen, L-NAcc, R-GP and L-SN were found to significantly predict psychosis in a Univariate Logistic Regression Model. Basal ganglia are affected from the first stage of the disease in schizophrenia, and it can be more possible that these changes are the result of pathogenesis schizophrenia.

The dynamic on-state resistance instability of a high-current cascode multi-GaN-chip power module under high frequency and voltage switching conditions is demonstrated in this paper. The presented double pulse test (DPT) topology is utilized to evaluate switching dependencies on voltage, current, and frequency, showing its versatility in investigating the switching instability of the device. The extended defects in the buffer layer resulted in a decrease in dynamic on-state resistance (RDS-ON) under hard switching conditions. Despite this, no noticeable RDS-ON degradation occurs under harsh switching conditions due to electron de-trapping. This study comprehensively analyzes the dynamic stability of a multi-GaN-chip cascode module with devices.

Neurodegenerative disorders are common among the elderly. They possess a tremendous therapeutic challenge for drug development and tackling the disease. Alzheimer's ranks as the most common neurodegenerative disease affecting the elderly population. Developing therapeutics is still a challenge despite advancements in the medical sciences. Replacing the small molecules that are used for Alzheimer's today, numerous Monoclonal antibodies and vaccines are tried that targets explicitly the disease pathology, either beta-amyloid or Tau aggregation. In this review, we try to shed light on the existing small molecule therapeutics and the recent advances with insights into Monoclonal antibodies and clinical trials.