According to the classical view of heredity, genes are the only bearers of genetic information. Nonetheless, there is mounting evidence to support the notion that biological systems, including epigenetic alterations, non-coding RNA molecules, and environmental variables, transmit information beyond genes. This “Inheritance of Information” idea contradicts the traditional notion of heredity and has profound consequences for our knowledge of medicine, evolution, and the basis of life itself. This article investigates the evidence supporting the Inheritance of Information hypothesis and its ramifications, including the possible creation of novel therapies for diseases that target epigenetic alterations, a more nuanced understanding of how species evolve and adapt to changing environments, and a revised definition of life as “informational replicators.”

A document by Chen Xinyu. Click on the document to view its contents.

Background and aim: The sedative role of dexmedetomidine (DEX) in gastrointestinal endoscopic procedures is unclear, highlighting the need to compare DEX with conventional sedatives for a full evaluation. We performed this systematic review and meta-analysis to assess the efficacy and safety of sedation with DEX alone or in combination during gastrointestinal endoscopic procedures with a view to providing guidance for clinical application. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched for randomized controlled trials from inception to July 1, 2022. Standardized mean difference and weighted mean difference with 95% confidence interval or pooled risk ratios with 95% CI was used for continuous outcomes or dichotomous outcomes, respectively, and a random-effect model was selected regardless of the significance of the heterogeneity. Results: Forty-one studies with 3,015 patients were assessed, of which 1,363 patients were in the DEX group and 1,652 patients were in the control (without DEX) group. We found that DEX administration decreased the risk of body movements or gagging, hypoxia, and cough, reduced the additional requirement for other sedatives, and increased the endoscopist satisfaction level, however, induction time, and risk of bradycardia, and without statistical differences in RSS score, patient satisfaction level, recovery time, hypotension, nausea, and vomiting. Conclusion: DEX may benefit patients undergoing gastrointestinal endoscopic procedures in some clinical outcomes, whilst some potential disadvantages also exist. Remarkably, DEX was non-inferior to midazolam and propofol in terms of sedation level. In conclusion, DEX is an alternative option for sedation in gastrointestinal endoscopic procedures.

In this work, a model for the characterization of microalgae cultures based on artificial neural networks has been developed. Data acquisition has been performed using FlowCam, a device capable of capturing images of the cells detected in a culture sample, which are used as inputs by the model. The model can distinguish between 6 different genera of microalgae, having been trained with several species of each genus. It was further complemented with a classification threshold to discard unwanted objects while improving the overall accuracy of the model. The results demonstrate the accuracy of the Deep Learning models for the characterization of microalgae cultures, it being a useful tool for the monitoring of microalgae cultures in large-scale production facilities.

IntroductionTumoral calcinosis (TC) is a rare clinicopathological entity characterized by the presence of calcified deposits in periarticular soft tissue. The calcified deposits predominantly comprise of calcium hydroxy apatite crystals and amorphous calcium phosphate1. Clinically, they appear as a painless slowly growing mass in the vicinity of large joints such as hips, shoulder, and elbow 2, 3. However, it has also been reported in other areas such as the neck, arms, hands, spine, legs, and feet 3. The progressive growth of the mass may result in pain, nerve compression, and functional impairment4. The overlying skin is usually intact; however, long-standing lesions may lead to skin ulceration and sinus tract formation with chalk white drainage 2.The diagnosis of TC is based on clinical and imaging findings. It has a characteristic radiographic appearance of multilobulated calcification in periarticular soft tissues, commonly on the extensor side of the articulation. Radiolucent lines separate the lobules (fibrous septa)5, 6. Ultrasound can be used to examine lesions, especially with minimal calcification, appearing as heterogeneous multiloculated mass with multiple cavities separated by hyperechoic thin septa. Color doppler may detect blood flow in some of these septa. MRI is superior to CT scan in detecting the extent of the lesions and their relationship with surrounding structures 6. However, histopathological examination is required for definitive diagnosis. Treatment options include both medical and surgical intervention5, 7.We present a case of tumoral calcinosis with peculiar presentation. A case of 4-year-old female with tumoral calcinosis of the extensor indicis proprius tendon on the right wrist.

As an important branch of the Internet of Things, Internet of Drones (loD) is changing the way of human life. However, loD suffer cyber attacks in practice. In 2021, Hussain et al. proposed an loD authentication scheme based on Elliptic Curve Cryptography (ECC) to solve this problem. Through analysis, their scheme is expensive to calculate and difficult to adapt to loD environment. As a result, a new lightweight authentication scheme based on secure one-way hash function and bitewise XOR operations was proposed. The experimental results show that the proposed scheme not only guarantees the safety, but also has lower computation cost. Thus, it is more suitable for loD.

Introduction: The influenza A virus nonstructural protein NS1 is crucial for the virus infection process. By interacting with various host RNAs or proteins, NS1 regulates both host and viral activities. Nucleolar and coiled-body phosphoprotein 1 (NOLC1), a protein involved in cell cycle regulation, may be involved in host viral resistance. The purpose of this study was to elucidate the changes in host NOLC1 during virus infection and the effect of these changes on virviral replication. Methods: We used co-immunoprecipitation to confirm that H1N1 NS1 can interact with NOLC1 in host cells. Results: We found that the D125 and R200 residues in H1N1 NS1 are crucial for the interaction. Real-time PCR and western blotting revealed changes in host NOLC1 during viral infection. Constructing a lentiviral vector, and then overexpressing and knocking down NOLC1 in A549 cells, enabled us to demonstrate how NOLC1 affects viral replication. We found that H1N1 NS1 interacts with host NOLC1 and that NOLC1 is inhibited during H1N1 infection. In NOLC1-knockdown A549 cells, viral replication was inhibited. Conclusion: The current study revealed that viral replication is negatively affected by a decrease in NOLC1 level in host cells. This research lays the foundation for a deeper comprehension of the mechanisms underlying the complex host–influenza virus interactions, as well as for the prevention and management of influenza viruses.

Mycobacterium tuberculosis (M. tuberculosis) is an intracellular bacteria capable of evading the human immune system through various mechanisms. M. tuberculosis secretes many virulence factors when infecting host cells. The 6 kDa early secretory antigen target (ESAT-6) is one of the most virulent factors producted by the ESX-1 system, which acts alone or in conjunction with culture filtrate protein 10 (CFP-10) to involve in host-pathogen interactions. ESAT-6 has been widely investigated in M. tuberculosis pathogenicity and vaccination. Nonetheless, little is known about its contribution to M. tuberculosis immune evasion and the involved cellular mechanisms. In this study, differential genes between BCG with the region of difference-1 (RD1) gene and Bacille Calmette-Guérin (BCG) infected dendritic cells (DC) were analyzed to reveal that ESAT-6, expressed in the RD1 region, involves host denfensive function of DC in response to BCG. In vitro evidence indicated that ESAT-6 (5 μg/ml) inhibits M. tuberculosis-induced apoptosis in THP-1(A) macrophages by suppressing TLR2 and via caspase-9 and caspase-3 endogenous pathways. It also inhibits the expression of IL-10, TNF-α, IL-12, and the phagocytosis of macrophages. Additionally, ESAT-6 suppresses the bactericidal activity of macrophages, including ROS production, and the killing of M. tuberculosis. In summary, these data suggest a central role of ESAT-6 in M. tuberculosis’s evasion from macrophage recognition, phagocytosis, killing, and apoptosis. Our work may provide a theoretical basis for exploring new molecular targets of M. tuberculosis both for innovative vaccines and therapeutic inventions.

Background: Observational studies have linked various exposures to ovarian cancer (OC) risk, but the findings are potential subject to reverse causation and confounding. Herein, we performed comprehensive Mendelian randomization (MR) analyses to systematicly evaluate potential causal associations of known and suspected influencing factors with risk of OC and six common histotypes. Methods: Two-sample MR analyses were applied to data from the genome wide association study summary results comprising a total of 25,509 women with epithelial OC and 40,941 controls of European descent in the Ovarian Cancer Association Consortium. Genetic instrumental variables associated with influencing factors were selected. Inverse-variance weighted method was used as the primary analysis, and the MR assumptions were evaluated in sensitivity analyses. MR-PRESSO method was applied for the detection and correction of potential horizontal pleiotropy. Results: OC and six histotypes were considered in this study. Of 100 known and suspected influencing factors, 7 lifestyle factors, 12 dietary factors, 4 reproductive factors, 12 body size factors, 3 comobidities, and 7 biomarkers were significantly associated with risk of OC. Among them, 26, 9, 25, 19, 5, 13, and 22 factors were associated with the risk of OC, clear cell OC, endometrioid OC, high grade serous OC, low grade serous OC, mucinous OC, and low malignant potential OC respectively. Conclusion: Our study adds to current knowledge on the causal effect of known and suspected influencing factors on OC and six histotypes. Further investigation is needed to better understand potential pathways or mechanisms of these factors.

This brief report describes the importance of close discussion between clinicians and scientists and progress in leukaemia genetic work-up to deliver optimal treatment to a girl with 2 episodes of childhood Acute Lymphoblastic Leukaemia. At initial presentation, limited cytogenetic analyses did not identify any recurrent genetic abnormalities and the patient was subsequently treated according to NCI risk criteria on regimen A of UKALL2003. Nine years later, she presented with low hypodiploid ALL which was associated with genetically confirmed Li-Fraumeni Syndrome. Genetic backtracking established late relapse of the initial ALL which was instrumental in informing treatment decisions.

Title : Cutaneous presentation of Candida krusei fungemia refractory to amphotericin BAuthors : Michelle Toker, BS1, Carson Kirkpatrick, MD1, Pooja Srivastava, MD1,2, Bijal Amin, MD1,2, Benedict Wu, DO, PhD1Affiliations :1- Division of Dermatology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA2- Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USACorresponding author :Michelle Toker, BSAlbert Einstein College of Medicine, Montefiore Medical Center1300 Morris Park Avenue, Bronx, New York, 10461Email: michelle.toker@einsteinmed.eduTelephone: 516-946-4726Funding and support : NoneConflicts of Interest : NoneManuscript word count : 599Reference count : 5Figure count : 2Table count : 0Key words : disseminated fungemia, candida, oncology, leukemia, cutaneous fungal infection, rash, pathology, infectious disease

Background: The effect of race, age, sex, atopy, environmental exposures, and social determinants of health on total serum immunoglobulin E (IgE) has not been examined in children with food allergy. Method: We conducted a cross-sectional analysis with univariable and multivariable linear mixed effect models of data from 398 African American and European American children 0-12 years with allergist-diagnosed food allergy from the multi-center, observational cohort FORWARD; total serum IgE in kU/L was the primary outcome measure. Results: Total serum IgE positively associated with African American race ( p < .0001), older age ( p < .0001), male sex ( p =. 0142), lower household income ( p = .0051), lower parent/caregiver education ( p = .0051), allergic rhinitis ( p < .0001), asthma ( p < .0001), eczema ( p = .0240), and a higher number of food allergies ( p < .0001), but not tobacco smoke exposure. After covariate adjustment in multivariable analysis, total serum IgE remained higher in African American than European American ( p < .0001), older than younger ( p < .0001), and male than female children and in children with allergic rhinitis ( p = .0083), asthma ( p < .0001), eczema ( p = .0140), and a higher number of food allergies ( p < .0001). Conclusions: We provide foundational data that total serum IgE varies by race in children with food allergy; values were higher in African American than European American children, independent of atopic status. These findings call attention to the need to establish race-dependent values of total serum IgE for diagnostic and therapeutic purposes.

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When a single-phase grounding fault occurs in a power distribution system, the fault characteristics are not prominent and are easily drowned out by noise, making fault line selection difficult. A fault line selection method based on improved empirical wavelet transform (EWT) and GIN network is proposed to solve this problem. Firstly, EWT is optimized using kurtosis as the basis and N-point search method. EWT decomposes the electrical signal into a series of modal components, and noise is filtered out by weighted permutation entropy to reconstruct the signal, obtaining a denoised electrical signal. Then, according to the topology of the power distribution network, a corresponding graph structure is constructed. The Mahalanobis distance between each point and the overall structure in the denoised electrical signal is calculated and used as the input to each node in the GIN network. Finally, the GIN network autonomously mines the characteristics of each graph structure, performs graph classification, and realizes fault line selection. Experimental results show that the proposed method has a solid anti-noise ability and an accuracy of up to 99.95%, effectively completing fault line selection in power distribution networks.

Tyler J. Gathman MS1,2, Ranveer M.S. Vasdev MS1,2, Miriam R. Smetak MD MS3, Anthony Williams MD MS1,4, Anna Budde MD1,5, Paul A. Iaizzo PhD1

There is a lot of focus on how Quantum Computing as an accelerator differs from other traditional HPC resources, including accelerators like GPUs and FPGAs. In classical computing, how to design the interfaces that connect the different layers of the software stack, from the applications and its high-level programming language description through compilers, schedulers, down to the hardware, and gate-level, has been critical. Likewise, quantum computing's interfaces enable the access to quantum technology as a viable accelerator. From the ideation of the quantum application to the manipulation of the quantum chip, each interface has its challenges. In this column feature, we discuss the structure of this set of quantum interfaces, their many similarities to the traditional HPC compilation stack, and how these interfaces impact the potential of quantum computers as HPC accelerators.

Background: Comprehensive primary healthcare through Ayushman Bharat- Health and Wellness Centres (HWCs) was initiated by Government of India in 2018. The present study explores performance variations among HWCs, and the reasons for the variations from a provider’s perspective. Methods: A sequential mixed methods study was conducted in Punjab state between April to September 2021. The quantitative facility assessments of 8 HWCs was followed by 16 in-depth interviews with the community health officers (CHOs) and Auxiliary midwives (ANMs) to understand their perceptions about service delivery. This was supplemented with physical observations, and desk review of administrative orders. A descriptive data analyses was carried out to identify variations in resources between the high and low-performing HWCs. A framework analyses was applied on qualitative data using the ‘Capacity, Opportunity, Motivation, Behaviour’ model. Results: There was significant difference in infrastructure at the high and low-performing HWCs, but the quantity of human resources was similar. The categories identified from the in-depth interviews that affected work performance were capacity, communication, opportunity, and motivation. Capacity was contingent on trainings, work experience, self-belief, role clarity, and level of communication between cadres, while supportive supervision and incentives affected the work motivation. Conclusion: Understanding and sharing of roles was poor in low performing HWCs. Appropriate facility designs considering the role of staff, improved communication at all levels of health system, and reappraisal of financial policies linked to HWCs are important for performance. There is a requirement to build management capacities in all HWCs to achieve work efficiency.

Obstetric fistula (OF) is a physically and psychologically debilitating medical condition that impacts vulnerable women in Tanzania. It occurs primarily as a result of prolonged labor, which leads to the formation of an abnormal opening between the bladder or rectum and the vagina, and can cause severe incontinence, stigma, and social isolation. Non-governmental organizations (NGOs) have been instrumental in providing assistance and support to vulnerable women with obstetric fistula in Tanzania. This study investigated the various interventions implemented by NGOs in Tanzania to help women suffering from obstetric fistula. The study aimed to identify the strategies employed by NGOs to address obstetric fistula among vulnerable women, as well as explore factors that influence the delivery of obstetric fistula services. By using the Comprehensive Community-Based Rehabilitation in Tanzania (CCBRT) as a case study, the study establishes that Tanzania’s largest provider of fistula surgery (CCBRT) has implemented various initiatives, including expansion of joint delivery services, an m-pesa mobile outreach program, an ambassadorial network, and an improvement of service quality, to assist vulnerable women, particularly those in remote areas. The study concludes that obstetric fistula is a debilitating condition that continues to affect vulnerable women in Tanzania, and NGOs have played a critical role in providing interventions to alleviate the impact of this condition on women in the country.

The parasite Plasmodium falciparum causes the most severe form of malaria and to invade and replicate in red blood cells (RBCs), it exports hundreds of proteins across the encasing parasitophorous vacuole membrane (PVM) into this host cell. The exported proteins help modify the RBC to support rapid parasite growth and avoidance of the human immune system. Most exported proteins possess a conserved Plasmodium Export Element (PEXEL) motif with the consensus RxLxE/D/Q amino acid sequence, which acts as a proteolytic cleavage recognition site within the parasite’s endoplasmic reticulum (ER). Cleavage occurs after the P 1 L residue and is thought to help release the protein from the ER so it can be putatively escorted by the HSP101 chaperone to the parasitophorous vacuole space surrounding the intraerythrocytic parasite. HSP101 and its cargo are then thought to assemble with the rest of a Plasmodium Translocon for Exported proteins (PTEX) complex, that then recognises the xE/D/Q capped N terminus of the exported protein and translocates it across the vacuole membrane into the RBC compartment. Here, we present evidence that supports a dual role for the PEXEL’s conserved P 2’ position E/Q/D residue, firstly, for plasmepsin V cleavage in the ER, and secondly, for efficient PTEX mediated export across the PVM into the RBC. We also present evidence that the downstream ‘spacer’ region separating the PEXEL motif from the folded functional region of the exported protein controls cargo interaction with PTEX as well. The spacer must be of a sufficient length and permissive amino acid composition to engage the HSP101 unfoldase component of PTEX to be efficiently translocated into the RBC compartment.

While the estimate of hospital costs concerns the past, its planning focus on the future. However, many public hospitals in low and middle-income countries don’t have robust accounting health systems to evaluate and project their expenses. In Brazil, public hospitals are funded based on government estimates of available hospital infrastructure, historical expenditures and population needs. However, these pieces of information are not always readily available for all hospitals. To solve this challenge, we propose a flexible simulation-based optimisation algorithm that integrates this dual task: estimating and planning hospital costs. The method was applied to a network of 17 public hospitals in Brazil to produce the estimates. Setting the model parameters for population needs and future hospital infrastructure can be used as a cost-projection tool for divestment, maintenance, or investment. Results show that the method can aid health managers in hospitals’ global budgeting and policymakers in improving fairness in hospitals’ financing.

Corilagin has several pharmacological effects such as anti-tumor, anti-inflammatory, and cardiovascular disease treatment. Our previous studies have shown that the Corilagin can significantly inhibit proliferation of HeLa cells. However, there is no scientific data on the anti-cervical cancer effect of Corilagin in vivo. It was speculated that the mechanism of action for the anti-cervical cancer of Corilagin could be related to PI3K/AKT and MAPK signaling pathways through network pharmacology. Results of cell assays in the present study showed that the Corilagin has significant effect on the proliferation, cell cycle and apoptosis of murine cervical cancer U14 cells in vitro. In addition, Corilagin can significantly inhibit the growth of U14 tumor-bearing mice with insignificant toxic effect on liver and kidney of the transplanted mice. The current study found that Corilagin can delay development of cervical cancer by boosting anti-tumor immune responses of body. RT-PCR and Western blotting were applied in the current study to evident that Corilagin can achieve anti-cervical cancer property by inducing apoptosis of tumor tissues through both PI3K/AKT and MAPK signaling pathways. Therefore, this study provided theoretical reference for research of Corilagin as a bio-resource for development of an anti-cervical cancer drug and functional food.

The objective of this study was to compare the financial data of AZA-accredited 501(c)(3) facilities with paid and unpaid internship programs. Financial data was collected from each facility’s 2018 Form 990 found from the IRS Tax Exempt Organization Tool. The data were analyzed to determine if there was a statistically significant difference in the distribution of each facility’s primary sources of revenue and expenses. Financial data was also collected and compared on total revenue, net income, average employee salary, and highest employee salary. There was no significant difference in the distribution of revenue and expenses found between facilities with compensated intern programs and uncompensated intern programs. There was also no significant difference in the total revenue and net income between facility types. The results indicate that all AZA-accredited 501(c)(3)s, regardless of size and operating budget, have the potential to create a compensated intern program. Facilities with compensated intern programs had a significantly greater average employee salary, suggesting that these facilities focus more on compensating staff overall. Facilities with compensated intern programs were interviewed to collect information on how these programs were created and funded. Most respondents said compensation needs to be prioritized and built directly into the annual budget. More research is recommended to determine why facilities are not compensating interns and if compensating interns will provide accessible pathways to zoo and aquarium careers.Marino. (2022). Zoos and Aquariums Can Pay Their Interns: Analyzing  Financial Data from 501(c)(3)s. Animal Keepers' Forum, 49(10), 280-286.

ChatGPT: First Glance from a Perspective of Clinical PharmacologyAuthors: Julie Rudbech Krumborg1,2, Nicolaj Mikkelsen1,2, Per Damkier1,2, Zandra Nymand Ennis1,2, Daniel Pilsgaard Henriksen1,2, Mads Lillevang-Johansen1,2, Sidsel Arnspang Pedersen1,2, Troels K Bergmann1,31. Department of Clinical Pharmacology, Odense University Hospital, Denmark2. Department of Clinical Research, Faculty of Health Science, University of Southern Denmark, Denmark3. Department of Regional Health Research, University of Southern Denmark, Esbjerg, DenmarkCorresponding author: Julie Rudbech Krumborg: Julie.Rudbech.Krumborg@rsyd.dkKeywords : Artificial intelligence, Clinical Pharmacology, Drug Information Services, evidence-based medicine, Medical WritingConflict of interest statement: The authors state no conflicts of interest

Objectives: Circulating nucleocapsid (NCP) antigen of SARS-CoV-2 is increased in severely ill COVID-19 patients. However, clinical deterioration of COVID-19 often happens about one week after benign initial presentation. The role of NCP antigenemia as a biomarker in those cases remains unclear. We investigated NCP clearance kinetics in hospitalized patients as a risk assessment tool for predicting necessity of intensive care treatment of COVID-19 patients. Methods: Serum NCP was quantified using a commercial NCP-specific ELISA in hospitalized COVID-19 patients (n=63) during their hospital stay. Results were correlated to COVID-19 disease severity, inflammation parameters, antibody response and results of SARS-CoV-2 PCR from nasopharyngeal swabs.   Results: We demonstrate that NCP antigen levels in serum remained elevated in 45.6% of patients requiring treatment on intensive care units (ICU) after >8 days post positive SARS-CoV-2 PCR, compared to complete clearance in all non-ICU patients. This was in contrast to mucosal clearance of virus as measured by PCR. Antigen clearance was associated with higher IgG against S1 but not NCP.   Conclusions: Detection of NCP antigenemia after 8 days post COVID-19 diagnosis identifies patients who will require intensive care. Lack of NCP clearance after one week can thus help to assess the risk to develop severe COVID-19.