CTCF as a regulator of alternative splicing: new tricks for an old player.

Three decades of research have established the CCCTC-binding factor (CTCF) as a ubiquitously expressed chromatin organizing factor and master regulator of gene expression. A new role for CTCF as a regulator of alternative splicing (AS) has now emerged. CTCF has been directly and indirectly linked to the modulation of AS at the individual transcript and at the transcriptome-wide level. The emerging role of CTCF-mediated regulation of AS involves diverse mechanisms; including transcriptional elongation, DNA methylation, chromatin architecture, histone modifications, and regulation of splicing factor expression and assembly. CTCF thereby appears to not only co-ordinate gene expression regulation but contributes to the modulation of transcriptomic complexity. In this review, we highlight previous discoveries regarding the role of CTCF in AS. In addition, we summarize detailed mechanisms by which CTCF mediates AS regulation. We propose opportunities for further research designed to examine the possible fate of CTCF-mediated alternatively spliced genes and associated biological consequences. CTCF has been widely acknowledged as the 'master weaver of the genome'. Given its multiple connections, further characterization of CTCF's emerging role in splicing regulation might extend its functional repertoire towards a 'conductor of the splicing orchestra'.

Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus.

Herein, we measured the antidiabetic and nephroprotective effects of the sodium-glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H2O2), pro-inflammatory (IL1ß/IL6/TNF-α), tissue damage (iNOS/TGF-ß1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms.

AES Based White Box Cryptography in Digital Signature Verification.

According to the standard paradigm, white box cryptographic primitives are used to block black box attacks and protect sensitive information. This is performed to safeguard the protected information and keys against black box assaults. An adversary in such a setting is aware of the method and can analyze many system inputs and outputs, but is blind to the specifics of how a critical instantiation primitive is implemented. This is the focus of white-box solutions, which are designed to withstand attacks that come from the execution environment. This is significant because an attacker may obtain unrestricted access to the program's execution in this environment. The purpose of this article is to assess the efficiency of white-box implementations in terms of security. Our contribution is twofold: first, we explore the practical implementations of white-box approaches, and second, we analyze the theoretical foundations upon which these implementations are built. First, a research proposal is crafted that details white-box applications of DES and AES encryption algorithms. To begin, this preparation is necessary. The research effort planned for this project also includes cryptanalysis of these techniques. Once the general cryptanalysis results have been examined, the white-box design approaches will be covered. We have decided to launch an investigation into creating a theoretical model for white box, since no prior formal definitions have been offered, and suggested implementations have not been accompanied by any assurance of security. This is due to the fact that no formal definition of "white box" has ever been provided. In this way lies the explanation for why this is the situation. We define WBC to encompass the security requirements of WBC specified over a white box cryptography technology and a security concept by studying formal models of obfuscation and shown security. This definition is the product of extensive investigation. This state-of-the-art theoretical model provides a setting in which to investigate the security of white-box implementations, leading to a wide range of positive and negative conclusions. As a result, this paper includes the results of a Digital Signature Algorithm (DSA) study which may be put to use in the real world with signature verification. Possible future applications of White Box Cryptography (WBC) research findings are discussed in light of these purposes and areas of investigation.

Ctcf haploinsufficiency mediates intron retention in a tissue-specific manner.

CTCF is a master regulator of gene transcription and chromatin organisation with occupancy at thousands of DNA target sites genome-wide. While CTCF is essential for cell survival, CTCF haploinsufficiency is associated with tumour development and hypermethylation. Increasing evidence demonstrates CTCF as a key player in several mechanisms regulating alternative splicing (AS), however, the genome-wide impact of Ctcf dosage on AS has not been investigated. We examined the effect of Ctcf haploinsufficiency on gene expression and AS in five tissues from Ctcf hemizygous (Ctcf+/-) mice. Reduced Ctcf levels caused distinct tissue-specific differences in gene expression and AS in all tissues. An increase in intron retention (IR) was observed in Ctcf+/- liver and kidney. In liver, this specifically impacted genes associated with cytoskeletal organisation, splicing and metabolism. Strikingly, most differentially retained introns were short, with a high GC content and enriched in Ctcf binding sites in their proximal upstream genomic region. This study provides new insights into the effects of CTCF haploinsufficiency on organ transcriptomes and the role of CTCF in AS regulation.

An Efficient Electronic Cash System Based on Certificateless Group Signcryption Scheme Using Conformable Chaotic Maps.

Signcryption schemes leveraging chaotic constructions have garnered significant research interest in recent years. These schemes have proffered practical solutions towards addressing the vast security vulnerabilities in Electronic Cash Systems (ECS). The schemes can seamlessly perform message confidentiality and authentication simultaneously. Still, their applications in emerging electronic cash platforms require a higher degree of complexity in design and robustness, especially as billions of online transactions are conducted globally. Consequently, several security issues arise from using open wireless channels for online business transactions. In order to guarantee the security of user information over these safety-limited channels, sophisticated security schemes are solely desired. However, the existing signcryption schemes cannot provide the required confidentiality and authentication for user information on these online platforms. Therefore, the need for certificateless group signcryption schemes (CGSS) becomes imperative. This paper presents an efficient electronic cash system based on CGSS using conformable chaotic maps (CCM). In our design, any group signcrypter would encrypt information/data with the group manager (GM) and send it to the verifier, who confirms the authenticity of the signcrypted information/data using the public criteria of the group. Additionally, the traceability, unforgeability, unlinkability, and robust security of the proposed CGSS-CCM ECS scheme have been built leveraging computationally difficult problems. Performance evaluation of the proposed CGSS-CCM ECS scheme shows that it is secure from the Indistinguishably Chosen Ciphertext Attack. Finally, the security analysis of the proposed technique shows high efficiency in security-vulnerable applications. Overall, the scheme gave superior security features compared to the existing methods in the preliminaries.

A Provably Secure IBE Transformation Model for PKC Using Conformable Chebyshev Chaotic Maps under Human-Centered IoT Environments.

The place of public key cryptography (PKC) in guaranteeing the security of wireless networks under human-centered IoT environments cannot be overemphasized. PKC uses the idea of paired keys that are mathematically dependent but independent in practice. In PKC, each communicating party needs the public key and the authorized digital certificate of the other party to achieve encryption and decryption. In this circumstance, a directory is required to store the public keys of the participating parties. However, the design of such a directory can be cost-prohibitive and time-consuming. Recently, identity-based encryption (IBE) schemes have been introduced to address the vast limitations of PKC schemes. In a typical IBE system, a third-party server can distribute the public credentials to all parties involved in the system. Thus, the private key can be harvested from the arbitrary public key. As a result, the sender could use the public key of the receiver to encrypt the message, and the receiver could use the extracted private key to decrypt the message. In order to improve systems security, new IBE schemes are solely desired. However, the complexity and cost of designing an entirely new IBE technique remain. In order to address this problem, this paper presents a provably secure IBE transformation model for PKC using conformable Chebyshev chaotic maps under the human-centered IoT environment. In particular, we offer a robust and secure IBE transformation model and provide extensive performance analysis and security proofs of the model. Finally, we demonstrate the superiority of the proposed IBE transformation model over the existing IBE schemes. Overall, results indicate that the proposed scheme posed excellent security capabilities compared to the preliminary IBE-based schemes.

DAMAC: A Delay-Aware MAC Protocol for Ad Hoc Underwater Acoustic Sensor Networks.

In a channel shared by several nodes, the scheduling algorithm is a key factor to avoiding collisions in the random access-based approach. Commonly, scheduling algorithms can be used to enhance network performance to meet certain requirements. Therefore, in this paper we propose a Delay-Aware Media Access Control (DAMAC) protocol for monitoring time-sensitive applications over multi-hop in Underwater Acoustic Sensor Networks (UASNs), which relies on the random access-based approach where each node uses Carrier Sense Multiple Access/Collision Avoidance (CSMA/CA) to determine channel status, switches nodes on and off to conserve energy, and allows concurrent transmissions to improve the underwater communication in the UASNs. In addition, DAMAC does not require any handshaking packets prior to data transmission, which helps to improve network performance in several metrics. The proposed protocol considers the long propagation delay to allow concurrent transmissions, meaning nodes are scheduled to transmit their data packets concurrently to exploit the long propagation delay between underwater nodes. The simulation results show that DAMAC protocol outperforms Aloha, BroadcastMAC, RMAC, Tu-MAC, and OPMAC protocols under varying network loads in terms of energy efficiency, communication overhead, and fairness of the network by up to 65%, 45%, and 726%, respectively.

An exome-first approach to aid in the diagnosis of primary ciliary dyskinesia.

Unlike disorders of primary cilium, primary ciliary dyskinesia (PCD) has a much narrower clinical spectrum consistent with the limited tissue distribution of motile cilia. Nonetheless, PCD diagnosis can be challenging due to the overlapping features with other disorders and the requirement for sophisticated tests that are only available in specialized centers. We performed exome sequencing on all patients with a clinical suspicion of PCD but for whom no nasal nitric oxide test or ciliary functional assessment could be ordered. Among 81 patients (56 families), in whom PCD was suspected, 68% had pathogenic or likely pathogenic variants in established PCD-related genes that fully explain the phenotype (20 variants in 11 genes). The major clinical presentations were sinopulmonary infections (SPI) (n = 58), neonatal respiratory distress (NRD) (n = 2), laterality defect (LD) (n = 6), and combined LD/SPI (n = 15). Biallelic likely deleterious variants were also encountered in AKNA and GOLGA3, which we propose as novel candidates in a lung phenotype that overlaps clinically with PCD. We also encountered a PCD phenocopy caused by a pathogenic variant in ITCH, and a pathogenic variant in CEP164 causing Bardet-Biedl syndrome and PCD presentation as a very rare example of the dual presentation of these two disorders of the primary and motile cilia. Exome sequencing is a powerful tool that can help "democratize" the diagnosis of PCD, which is currently limited to highly specialized centers.

HLA-DQB1*06:02 allele frequency and clinic-polysomnographic features in Saudi Arabian patients with narcolepsy.

BACKGROUND: Narcolepsy is an uncommon neurological disorder characterised by irresistible spells of sleep associated with abnormal rapid eye movement (REM) sleep. The association between narcolepsy and human leukocyte antigen HLA- DQB1*06:02 has been established elsewhere but remains to be investigated among Saudi Arabian patients with narcolepsy. METHODS: A total of 29 Saudi patients with type I or type 2 narcolepsy comprising of 23 (79%) males and 6 (21%) females with a mean age of 17.2 ± 9.6 years were included in this study. Type 1 or type 2 narcolepsy was diagnosed by full polysomnography followed by a multiple sleep latency test in accordance with International Classifications of Sleep Disorders-3 criteria. HLA typing for DQB1 alleles was performed by polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes. Differences in clinical and sleep parameters were compared by univariable analyses. HLA-DQB1*06:02 frequency was systematically compared with the published literature. RESULTS: Type 1 narcolepsy was diagnosed in 19/29 (65.5%) patients, whereas 10/29 (34.5%) patients had type 2 narcolepsy. DQB1*06:02 was present in 25/29 (86.2%) patients; 15/19 (78.9%) narcolepsy type 1 patients and 10/10 (100%) narcolepsy type 2 patients harboured the DQB1*06:02 allele. REM latency was significantly lower in DQB1*06:02-positive patients compared to DQB1*06:02-negative patients (17.6 ± 32.3 min vs. 106.0 ± 86.0 min; p = 0.025). Epworth Sleepiness Scale scores were significantly higher among type 1 than type 2 narcolepsy patients (19.7 ± 3.2 vs 15.3 ± 3.6; p = 0.02). CONCLUSIONS: DQB1*06:02 allele frequencies among Saudi patients with narcolepsy were consistent with previously published data.

Assessment of a Bracket-Bonding System's Shear Bond Strength after it has been Cured using Various Light-Curing Units at Different Time Intervals.

Objectives: To assess a bracket-bonding system's shear bond strength cured with dissimilar light-curing units at different time intervals. Materials and Method: Sixty premolar teeth removed for orthodontic purposes were categorized into four types based on the light-curing unit and exposure times used. The specimens in the halogen group were exposed to light for 15 (Group I) and 30 (Group II) sec, respectively. The specimens were exposed to light for 10 (Group III) and 15 sec in the LED group (Group IV). The amount of adhesive still present on the teeth was measured using a stereomicroscope at a magnification of 10 and was then assessed with the help of adhesive remnant index (ARI). Result: The group with the highest mean SBS was in Group II followed by Group I, Group III, and the group with the lowest mean SBS. The ARI was unaffected by the light-curing technique, with score 2 predominating. Conclusion: In all groups, polymerization using halogen and LED led to SBS values that were clinically suitable for orthodontic procedures.

Knowledge and Practice of Foot Care among Patients with Diabetes Attending Diabetes Center, Saudi Arabia.

Background: Diabetic foot is a serious and often debilitating diabetes complication that poses a significant risk of morbidity and even mortality. However, ensuring good knowledge and good practice of appropriate foot care for patients with diabetes has been frequently neglected in diabetes management. Objectives: This study aimed to assess foot care knowledge and practice in patients with diabetes. Methods: We conducted a cross-sectional study on 400 patients with diabetes at Madinah Diabetes Center, Madinah City, Saudi Arabia, in 2023. Sociodemographic, knowledge score, practice of foot care, and diabetes-related data were collected using a valid interview structured questionnaire. The prevalence of good knowledge and practice level was calculated and compared using the studied patients' characteristics using appropriate statistical tests. Results: The prevalence of good knowledge of foot care and its practice was 35% and 27%, respectively. The knowledge level showed statistically significant differences among patients based on their age and diabetes type and duration. Patients who were >50 years (70.1%), had type 2 diabetes (89.5%), and with diabetes duration >10 years (65%) showed significantly better knowledge. Female patients (65.7%) had a higher good practice level compared with male patients (34.3%) (p < 0.001). Conclusions: This study highlights the insufficient knowledge and inadequate foot care practice among patients with diabetes in the studied population. Educational interventions and targeted strategies are necessary to improve knowledge about the importance of foot care and promote better foot care practices among patients with diabetes.

The Correlation of Paternal Age on Semen Parameters in Assisted Reproduction: A Retrospective Study in Qassim, Saudi Arabia.

INTRODUCTION: In the past, fertility concerns have predominantly revolved around the effect of a woman's age on the quality of her eggs and the success of her pregnancy. While men generally retain their ability to father children throughout their lives, there is evidence suggesting a decline in natural conception rates as paternal age increases. A growing body of research indicates a potential link between advanced paternal age (APA) and various adverse outcomes, including changes in sperm genetics, reduced conception rates, higher rates of miscarriage, lower live birth rates, and even long-term health consequences in offspring. However, it remains unclear whether there is an association between APA and the effectiveness of assisted reproductive technology (ART). This study aims to shed light on the relationship between APA and semen parameters. METHODOLOGY: This is a retrospective, descriptive study analyzing data from electronic medical records of men undergoing ART at a fertility clinic in Saudia Arabia (2017-2022). Men aged 21-60 with at least one semen analysis and no missing data/hormonal treatment were included. Data on age and semen parameters (count, motility, and morphology) were extracted and analyzed using Jeffreys's Amazing Statistics Program (JASP; University of Amsterdam, Amsterdam, Netherlands) (descriptive statistics, Spearman's rank correlation). RESULTS: Analysis of 1506 men undergoing ART revealed a mean age of 37 years (SD=6.94) and a mean sperm count of 55.0 million/mL (SD=46.05). The correlation between age and sperm count indicates a minimal association (r=0.075, p<0.01); moderate positive correlations were observed between sperm count and motility (r=0.406); count and morphology (r=0.543); and motility and morphology (r=0.458). CONCLUSION: Age may not be a major factor in overall sperm parameters for this population, but a strong positive correlation was observed between sperm count, motility, and normal morphology. These findings suggest that these semen parameters are interconnected, with higher sperm counts potentially indicating better overall sperm quality.

Respiratory Syncytial Virus (RSV) Burden in Infants in the Kingdom of Saudi Arabia and the Impact of All-Infant RSV Protection: A Modeling Study.

INTRODUCTION: Respiratory syncytial virus (RSV) represents a considerable burden on the healthcare system and hospital resources. This study explored the impact of universal immunoprophylaxis with long-acting monoclonal antibody (nirsevimab) during infants' first RSV season on RSV-induced health events and related costs in the Kingdom of Saudi Arabia (KSA). METHODS: The burden of RSV-induced health events and related costs under the current standard of practice (SoP) and the impact of universal immunoprophylaxis with nirsevimab was estimated using a static decision-analytic model in a cohort of infants experiencing their first RSV season in the KSA. The model estimated hospital admissions (including pediatric intensive care unit [PICU] admissions and mechanical ventilation [MV]), emergency room (ER) visits, primary care (PC) visits, long-term sequelae, and RSV mortality. RESULTS: The model estimated that under the current SoP, RSV results in 17,179-19,607 hospitalizations (including 2932-3625 PICU and 172-525 MV admissions), 57,654-191,115 ER visits, 219,053-219,970 PC visits, 14 deaths, 12,884-14,705 cases of recurrent wheezing, and a total cost of SAR 480-619 million. Universal nirsevimab immunoprophylaxis was estimated to avert 58% of hospitalizations (58% PICU admissions, 58% MV episodes), 53% of ER visits, 53% of PC visits, 58% of episodes of recurrent wheezing, 8 deaths, and result in savings of SAR 274-343 million in total healthcare cost. CONCLUSION: Compared with current SoP, an nirsevimab immunoprophylaxis strategy in the KSA for all infants during their first RSV season was estimated to dramatically decrease healthcare resource use, and economic burden associated with RSV.

Utility of Multimodal Treatment Protocols in the Management of Scalp Cutaneous Angiosarcoma.

Cutaneous angiosarcomas are rare, aggressive tumors with high recurrence and poor prognosis. We share our experiences with the challenging surgical management of these lesions, focusing on both ablative and reconstructive outcomes. Methods: Retrospective cross-sectional chart review was conducted of patients diagnosed with scalp cutaneous angiosarcoma between 2005 and 2021. Resectability, defect reconstruction, and survival outcomes were analyzed. Results: Thirty patients were included, 27 (90%) men and three (10%) women, with a mean age at diagnosis of 71.77 ± 7.3 years, and mean follow-up of 429.43 ± 305.6 days. Only 12 patients completed their regular follow-up, while the remaining patients died. There was a median survival of 443.50 days (range, 42-1283) and median time to recurrence of 21 days (range, 30-1690). Multimodal therapy compared with surgery alone had a significantly better overall median survival (468 days versus 71 days; P = 0.021). Defect coverage was obtained in 24 cases (75%) through an anterolateral thigh flap, two patients (6%) with a local transposition flap, and one patient (3%) with a transverse rectus abdominis myocutaneous flap. The remaining three patients received a skin graft. All of the flaps survived, with one requiring a vein graft for venous congestion. Conclusions: Timely multimodal therapy with a histologically safe margin, combined with adjuvant therapy, improves survival and delays recurrence and metastasis, in cutaneous angiosarcoma patients. An anterolateral thigh flap facilitates the coverage of wide defects. Further investigations of advanced treatment modalities such as immunotherapy and/or gene therapy are required to deal with this highly aggressive tumor.

Initial Outcomes of Freehand Transperineal Biopsies Regarding Diagnostic Value and Safety: An Early Experience at King Fahad Specialist Hospital, Buraydah, Saudi Arabia.

BACKGROUND: Prostate cancer is a common type of cancer in Saudi Arabia with a high incidence rate. Trans-rectal ultrasound guided prostatic biopsy (TRUSBx) has been the standard diagnostic study for prostate cancer since a landmark study in 1989 which showed that it is better than digitally directed biopsy sampling of the prostate. As an alternative to TRUSBx, transperineal biopsies (TPBx) have gained popularity as they give a higher accuracy rate and avoid many complications. A new study has been conducted in Riyadh, Saudi Arabia to compare TRUSBx and TPBx showed that TPBx has a significantly higher detection rate of prostate cancer cases compared to TRUSBx (45.1% vs. 29.1%, p=0.003). The aim of this study is to determine the diagnostic value and safety of freehand transperineal prostate biopsy in patients with an elevated prostatic specific antigen (PSA) and/or abnormal digital rectal exam in King Fahad Specialist Hospital KFSH in Buraydah, Qassim region, Saudi Arabia. METHODS: This is an observational retrospective study of all patients (n=39) who underwent transperineal biopsies at KFSH to assess the diagnostic value and safety of the procedure. RESULTS: The mean age of the patients was 70.3 (SD 10.1) years. The most commonly found diagnosis was adenocarcinoma (61.5%), and incidence of complications was detected in (5.1%) of the patients. CONCLUSION: We concluded that the freehand technique TPBx has a high accuracy rate in detecting prostatic cancer. However, the learning curve could be a limiting factor in implementing it. Increasing the number of biopsies could positively affect diagnostic accuracy, especially with our low complication rate in this procedure. A low number of biopsies in the older age group can give an accurate result with a low risk of complications. Although template-guided TPBx and robot-guided TPBx are better options, the freehand technique represents a cost-effective and time-saving alternative. However, more studies are needed to compare the outcome of such a technique.

Prevalence of malocclusion and orthodontic treatment needs among adolescents in Najran City, Saudi Arabia.

AIM: To determine the prevalence of malocclusions and the need for orthodontic treatment in a sample of school-going adolescents in the Najran city, Kingdom of Saudi Arabia (KSA). METHODOLOGY: This cross-sectional study was conducted among 1094 school-going Saudi male adolescents. The age range of the sampled adolescents was 13-18 years, and none of them had any history of orthodontic treatment. A survey chart related to malocclusion was designed and filled up after clinical examination by a single experienced and calibrated examiner. The need for orthodontic treatment was assessed using the Index of Orthodontic Treatment Need (IOTN). RESULT: The present study's findings demonstrated 61.2% of the samples with Angle's Class I malocclusions, 27.5% with Class II, and 11.4% of samples with Class III malocclusion. A significant difference was observed between the different classes of malocclusion (P < 0.001). Most samples presented normal overjet, crossbite, and no reverse overjet, deep bite, or open bite. The number of samples with no treatment need was 573 (52.37%), with slight treatment in 185 (16.91%) samples, moderate treatment needs in 123 (11.24%) samples, and severe and extreme treatment needs were 109 (9.96%) and 104 (9.50%), respectively. A significant difference was observed between the samples with no or slight treatment need (grades 1 and 2), moderate need (grade 3), and definite treatment need (grades 4 and 5) (p < 0.001). CONCLUSION: The prevalence of malocclusion and IOTNs among the sample of school-going adolescents in the Najran city was 47.63%. However, 9.63% of those samples required immediate attention for orthodontic treatment.

Impact of COVID-19 Pandemic on Respiratory Syncytial Virus (RSV) Prophylaxis Program: A Tertiary-Care Center Experience.

OBJECTIVES: The purpose of this investigation was to evaluate the effects of the COVID-19 pandemic on the respiratory syncytial virus (RSV) prevention program at our institution across three time frames: 2019-2020, 2020-2021, and 2021-2022. METHODS: We carried out a descriptive, single-site observational study spanning four years, from June 2019 to June 2022. Our study included patients in our institution's RSV program who met our enrollment criteria. We collected information about the number of children receiving immunoprophylaxis, immunoprophylaxis doses, and RSV risk factors. RESULTS: The number of patients receiving immunoprophylaxis dropped across the three periods, from 315 patients in the first period (2019-2020) to 176 in the second period (2020-2021), and further decreased to 128 in the third period (2021-2022). Following the COVID-19 pandemic, there was a 50% reduction in the number of patients receiving immunoprophylaxis. The proportion of RSV-infected patients remained relatively similar in the first and second periods (2.86% and 2.27%, respectively) but increased in the third period (5.47%). In the first period, most patients (60.32%) received seven doses, 11.75% got four to six doses, and 27.95% received three doses or fewer. The second period saw 59.66% of patients receiving four to six doses and 40.34% receiving three doses or fewer. In the third period, a mere 9.38% received four to five doses, while 90.63% got three doses or fewer. CONCLUSIONS: While preventative measures associated with COVID-19 may have helped reduce the number of RSV cases, the pandemic seems to have caused a significant decrease in the number of children receiving immunoprophylaxis and the doses of immunoprophylaxis. More extensive, multicenter research is needed to understand the impact of the COVID-19 pandemic on RSV immunoprophylaxis, its activity, and seasonal patterns fully.

Generation of myoglobin (MB)-knockout human embryonic stem cell (hESC) line (KAIMRCe002-A-1S) using CRISPR/Cas9 technology.

Myoglobin (MB) is a cytoplasmic hemoprotein that is predominantly expressed in the heart and oxidative myofibers of skeletal muscle. It has been demonstrated that MB binds to oxygen and promotes its diffusion for energy production in the mitochondria. Recently, MB was found to be expressed in different forms of malignant tumors and cancer cell lines. Further studies using gene disruption technology will enhance the understanding of MB's role in human cardiovascular biology and cancers. Here, we describe the generation of a homozygous MB knockout in human embryonic stem cells (hESC-MB-/-) via CRISPR/Cas9 to study MB function in human biology and diseases.

Balancing selection at the human salivary agglutinin gene (DMBT1) driven by host-microbe interactions.

Discovering loci under balancing selection in humans can identify loci with alleles that affect response to the environment and disease. Genome variation data have identified the 5' region of the DMBT1 gene as undergoing balancing selection in humans. DMBT1 encodes the pattern-recognition glycoprotein DMBT1, also known as SALSA, gp340, or salivary agglutinin. DMBT1 binds to a variety of pathogens through a tandemly arranged scavenger receptor cysteine-rich (SRCR) domain, with the number of domains polymorphic in humans. We show that the signal of balancing selection is driven by one haplotype usually carrying a shorter SRCR repeat and another usually carrying a longer SRCR repeat. DMBT1 encoded by a shorter SRCR repeat allele does not bind a cariogenic and invasive Streptococcus mutans strain, in contrast to the long SRCR allele that shows binding. Our results suggest that balancing selection at DMBT1 is due to host-microbe interactions of encoded SRCR tandem repeat alleles.

Smart Healthcare System with Light-Weighted Blockchain System and Deep Learning Techniques.

A radio communication sensor system is a collection of sensor modules that are connected to one another through wireless communication. It is common for them to be battery-powered and responsive to a nearby controller, referred to as the base station. They are capable of doing basic computations and transferring information to the base station in most scenarios. They are also in charge of transporting data from distant nodes, putting a burden on nodes with limited resources, and contributing to the quick depletion of energy in these nodes in the process. Nodes in close proximity to the base station are responsible for more than only detecting and sending data to the base station; they are also responsible for transmitting data from faraway nodes. To reward nodes that perform well, a protocol known as the Improved Fuzzy Inspired Energy Effective Protocol (IFIEEP) employs three separate sorts of nodes in order to provide more energy to those who do not. It takes into account the remaining node energy, the node's proximity to the base station, the node's neighbor concentration, and the node's centrality in a cluster when determining node viability. All of these assumptions are founded on a shaky understanding of the situation. Adaptive clustering must be applied to the most viable nodes in order to identify cluster leaders and transmit data to the base station, in addition to disseminating data across the rest of the network, in order to achieve success. In addition, the research provides proper heterogeneity parameters, which describe, among other things, the number of nodes as well as the starting energy of each node. The percentage gain in-network lifetime when compared to current approaches is minor for smaller numbers of supernodes; however, the percentage gain in the area covered 12.89 percent and 100% when more significant numbers of super nodes are used. These improvements in stability, residual energy, and throughput are accomplished by combining these improvements while also taking into consideration the previously neglected energy-intensive sensing energy aspect. The protocol that has been presented is meant to be used in conjunction with applications that make use of blockchain technology.