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Abstract The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.

Ancient schwannomas are a rare variation of schwannomas, with the distinction being based on histopathological examination of the excised specimen. On histopathological examination, ancient schwannomas exhibit degenerative changes such as calcification, hyalinization, and cystic necrosis, along with S100 positivity. Complete surgical excision is the mainstay treatment for ancient schwannomas and carries a favorable prognosis. Recurrence is the most common complication, often arising from incomplete surgical excision. Herein, we present a case of a 41-year-old male who presented to our center as a case of a retroperitoneal mass for further investigations and diagnostic workup. Imaging showed a retroperitoneal mass in the right iliac fossa. We proceeded with ultrasound guided needle biopsy, and examination of the specimen confirmed the diagnosis of ancient schwannoma. Subsequently, the patient underwent surgery, and complete surgical excision was achieved. On follow-up 3-months later, the patient is doing well, and no signs of recurrence were found.

The utilization of human cDNA libraries in yeast genetic screens is an approach that has been used to identify novel gene functions and/or genetic and physical interaction partners through forward genetics using yeast two-hybrid (Y2H) and classical cDNA library screens. Here, we summarize several challenges that have been observed during the implementation of human cDNA library screens in Saccharomyces cerevisiae (budding yeast). Upon the utilization of DNA repair deficient-yeast strains to identify novel genes that rescue the toxic effect of DNA-damage inducing drugs, we have observed a wide range of transcripts that could rescue the strains. However, after several rounds of screening, most of these hits turned out to be false positives, most likely due to spontaneous mutations in the yeast strains that arise as a rescue mechanism due to exposure to toxic DNA damage inducing-drugs.The observed transcripts included mitochondrial hits, non-coding RNAs, truncated cDNAs, and transcription products that resulted from the internal priming of genomic regions. We have also noticed that most cDNA transcripts are not fused with the GAL4 activation domain (GAL4AD), rendering them unsuitable for Y2H screening. Consequently, we utilized Sanger sequencing to screen 282 transcripts obtained from either four different yeast screens or through direct fishing from a human kidney cDNA library. The aim was to gain insights into the different transcription products and to highlight the challenges of cDNA screening approaches in the presence of a significant number of undesired transcription products. In summary, this study describes the challenges encountering human cDNA library screening in yeast as a valuable technique that led to the identification of important molecular mechanisms. The results open research venues to further optimize the process and increase its efficiency.

Background Despite optimal medical therapy, a significant proportion of patients' blood pressure remains uncontrolled. Catheter‐based renal denervation (RDN) has been proposed as a potential intervention for uncontrolled hypertension. We conducted an updated meta‐analysis to assess the efficacy and safety of RDN in patients with uncontrolled hypertension, with emphasis on the differential effect of RDN in patients on and off antihypertensive medications. Methods and Results Online databases were searched to identify randomized clinical trials comparing efficacy and safety of RDN versus control in patients with uncontrolled hypertension. Subgroup analyses were conducted for sham‐controlled trials and studies that used RDN devices that have gained or are currently seeking US Food and Drug Administration approval. Fifteen trials with 2581 patients (RDN, 1723; sham, 858) were included. In patients off antihypertensive medications undergoing RDN, a significant reduction in 24‐hour ambulatory (−3.70 [95% CI, −5.41 to −2.00] mm Hg), office (−4.76 [95% CI, −7.57 to −1.94] mm Hg), and home (−3.28 [95% CI, −5.96 to −0.61] mm Hg) systolic blood pressures was noted. In patients on antihypertensive medications, a significant reduction was observed in 24‐hour ambulatory (−2.23 [95% CI, −3.56 to −0.90] mm Hg), office (−6.39 [95% CI, −11.49 to −1.30]), home (−6.08 [95% CI, −11.54 to −0.61] mm Hg), daytime (−2.62 [95% CI, −4.14 to −1.11]), and nighttime (−2.70 [95% CI, −5.13 to −0.27]) systolic blood pressures, as well as 24‐hour ambulatory (−1.16 [95% CI, −1.96 to −0.35]), office (−3.17 [95% CI, −5.54 to −0.80]), and daytime (−1.47 [95% CI, −2.50 to −0.27]) diastolic blood pressures. Conclusions RDN significantly lowers blood pressure in patients with uncontrolled hypertension, in patients off and on antihypertensive medications, with a favorable safety profile. The efficacy of RDN was consistent in sham‐controlled trials and contemporary trials using US Food and Drug Administration–approved devices.

Coronary calcified lesions are commonly encountered and coronary atherectomy is commonly used for lesion modification during percutaneous coronary interventions (PCI). The release of adenosine during atherectomy can result in bradyarrhythmias and aminophylline is commonly used to prevent this reaction. We identified 138 patients to evaluate the safety and efficacy of intravenous (IV) aminophylline administration prior to coronary atherectomy. A total of 159 calcified lesions were treated, and the atherectomy device was orbital atherectomy, rotational atherectomy, and both in 52 %, 42 %, and 6 %; respectively. After administration of aminophylline, 4.3 % of patients required intraprocedural insertion of a transvenous pacer (TVP), and 18.1 % of patients required administration of IV atropine. Technical success was achieved in 98.6 % of patients, and no adverse reactions to aminophylline were reported. All patients survived to discharge. In conclusion, aminophylline administration prior to coronary atherectomy was safe and effective. No adverse effects of aminophylline were seen, and the rate of bailout TVP placement was low.

Literature reporting on the outcomes of the different procedures of nephrectomies (open vs laparoscopic vs robotic) in Saudi Arabia remains limited. Compare surgical and oncological outcomes between open and minimally invasive nephrectomies. A retrospective cohort study. The present study included all adult patients who underwent nephrectomies between January 1, 2015 and January 31, 2023. We collected demographic, preoperative, intraoperative, and postoperative data on 408 adult cancer patients who underwent nephrectomies at our center between January 2015 and January 2023. Statistical differences were calculated between procedure types. Overall survival was calculated using Kaplan–Meier curves with log-rank tests. P

IntroductionSociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States.MethodsMortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban–rural status, and geographic region using a significance level of p < 0.05.ResultsOverall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3–4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West.DiscussionSignificant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Abstract Background The nucleoside transport capabilities of the human equilibrative nucleoside transporter-3 (hENT3) are disrupted by mutations in SLC29A3 (10q22.2), which are genes for the nucleoside transporter and are the cause of the unusual autosomal recessive disease known as H syndrome. As a result, histiocytic cells invade a number of organs. Case presentation A 17-year-old Syrian male was admitted to the internal medicine department with a one-month history of polyuria, polydipsia, general weakness, and pallor. He had a history of progressive bilateral sensorineural hearing loss and failure to gain weight for three years. Physical examination revealed various abnormalities, including scrotal mass, small penis and testicles, absence of pubic and axillary hair, joint abnormalities, short stature, hallux valgus, fibrous protrusion near the navel, and hyperpigmented non-itchy painful skin plaques. Clinical signs along with laboratory test results confirmed hyperglycemia, primary hypogonadism, osteopenia, and growth hormone deficiency. After a review of the relevant medical literature, this patient’s presentation of hyperglycemia with hypogonadism, hyperpigmentation, hallux valgus, hearing loss, hematological abnormalities, and short stature suggested the diagnosis of H syndrome. The patient received treatment with insulin and testosterone, leading to a significant improvement in his presenting symptoms. Conclusions H syndrome is a very rare condition, and the fact that the first case has only recently been reported in Syria serves to emphasize how rare it is. H Syndrome should be suspected if a patient has short stature with signs of hyperglycemia and other endocrine and cutaneous abnormalities. We are reporting this case to increase physicians’ awareness of this exceedingly rare and unique syndrome.

AbstractThe two main forms of healthcare data exchange among entities are business-to-business (B2B) and business-to-customer (B2C). The former uses the electronic data interchange (EDI) technology between healthcare institutions, while the latter is usually conducted by providing web-based interfaces for patients. This research argues that both forms have inherent security and privacy weaknesses. Furthermore, patients lack appropriate transparency and control over their own Personally Identifiable Information (PII). We explore the issues of medical record exchange, analyze them and suggest appropriate solutions in the form of a new model to mitigate them. The vulnerabilities, ranging from critical to minor, include the possibility of Man-in-The-Middle (MiTM) and supply chain attacks, weak cryptography, repudiable transactions, single points of failure (SPOF), and poor access controls. A novel model will be presented in this research for healthcare data sharing which applies the best security practices. The proposed unified model will counter the listed vulnerabilities. It automates the healthcare processes in decentralized architecture by utilizing the smart contracts for B2C transactions such as medicine purchase. The model is based on the Blockchain and zero-knowledge proofs. It is made with novel controls which represent the latest advancements in cybersecurity. It has the potential of setting a new cornerstone.

Background: Lifestyle choices significantly affect health outcomes in Saudi Arabia, but the relationship between health behaviors and satisfaction is unclear. This study aimed to assess lifestyle choices and associated satisfaction levels among residents in the Jazan region of Saudi Arabia. Methods: A cross-sectional study was conducted in Jazan, Saudi Arabia, with 3411 participants. Sociodemographic, lifestyle, and satisfaction data were collected using a questionnaire that was completed during interviews. Logistic regression analyses were implemented to examine the relationships between the study variables and factors related to weight, physical activity, and eating satisfaction. Results: The study found that 38.3% of participants were inactive and 77% rarely ate fruits and vegetables. A total of 47.6% were overweight or obese. Weight (71.12%) and eating (71.59%) satisfaction were high despite these health concerns. The satisfaction-behavior paradox was especially evident in diet. Higher income, physical activity, and healthy eating habits were significantly associated with higher satisfaction (OR = 1.49, 95% CI: 1.15–1.93, p = 0.003 for weight satisfaction, OR = 34.74, 95% CI: 25.42–48.35, p < 0.001 for physical activity satisfaction, and OR = 2.08, 95% CI: 1.67–2.61, p < 0.001 for fruit and vegetable consumption). Conclusions: Lifestyle behaviors and satisfaction in Jazan, Saudi Arabia, are complex. The satisfaction-behavior paradox, especially in diet, reveals a major gap between perceived and actual health. These findings highlight the need for targeted, culturally sensitive interventions that address behavioral change and perception alignment to improve regional public health.

Coordinating humanitarian supply chains can be challenging in terms of getting timely aid to those who need it. While operations in commercial supply chains have been well studied, research studies that address coordination in humanitarian supply chains are still lacking. Unlike commercial supply chains, humanitarian supply chains focus on delivering what customers "need" rather than "want" within difficult environments rife with uncertainty. This paper introduces the "Humanitarian Aid and Relief Distribution (HARD) Game" as an experiential learning tool that explores the potential for increased operational efficiency while balancing decision tradeoffs impacting humanitarian supply chain performance, including beneficiary demand satisfaction, operational costs, and transportation resources utilization. The HARD game is intended for graduate and undergraduate students in courses dealing with topics on supply chain management. It allows students to analyze aspects that significantly impact humanitarian supply chain operations, such as: supply chain coordination and planning, supply chain risks, demand volatility, and competing objectives. Statistical analysis of students' survey responses provide evidence that the HARD game is an effective pedagogical tool that is engaging for students and complementary to the traditional lecture format in the field of supply chain management education.

BackgroundHigher prevalence of obesity has been observed among women compared to men, which can be explained partly by the higher consumption of sweets and physical inactivity. Obesity can alter immune cell infiltration, and therefore increase the susceptibility to develop chronic inflammation and metabolic disorders. In this study, we aimed to explore the association between free sugar intake and other unhealthy lifestyle habits in relation to the proportion of circulating iNKT cells among women with healthy weight and women experiencing overweight and obesity.MethodsA cross-sectional study was conducted on 51 Saudi women > 18 years, wherein their daily free sugar intake was assessed using the validated Food Frequency Questionnaire. Data on smoking status, physical activity, and supplement use were also collected. Anthropometric data including height, weight, waist circumference were objectively measured from each participants. The proportion of circulating iNKT cells was determined using flow cytometry.ResultsSmoking, physical activity, supplement use, and weight status were not associated with proportion of circulating iNKT cells. Significant association was found between proportion of circulating iNKT cells and total free sugar intake and free sugar intake coming from solid food sources only among women experiencing overweight and obesity (Beta: -0.10: Standard Error: 0.04 [95% Confidence Interval: -0.18 to -0.01], p= 0.034) and (Beta: -0.15: Standard Error: 0.05 [95% Confidence Interval: -0.25 to -0.05], p= 0.005), respectively.ConclusionExcessive free sugar consumption may alter iNKT cells and consequently increase the risk for chronic inflammation and metabolic disorders.

Gallbladder cancer (GBC) is a rare and highly aggressive malignancy, often characterized by nonspecific clinical presentations and late diagnosis, which contribute to its poor prognosis. It is commonly detected at advanced stages, leading to low survival rates. Surgical resection is the primary treatment, with the extent of surgery depending on the T stage of the cancer. In advanced cases, surgery is only considered if it can potentially be curative. Despite various treatment approaches for advanced GBC, survival outcomes remain poor. In our case series, we introduce a novel treatment approach combining cytoreductive surgery, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Remarkably, we observed a 100% one-year survival rate, with one patient achieving eight years of disease-free survival without recurrence or metastasis. This aggressive treatment strategy did not lead to increased morbidity or mortality, suggesting its safety and feasibility. However, larger-scale studies are required to draw definitive conclusions.

Key Clinical Message However, it is noteworthy that certain patients with minor functional limitations in their hand may have experienced undiagnosed thumb hypoplasia during their childhood years. These individuals may have successfully adapted to their condition without seeking medical intervention and may express a preference for nonintervention (as in this case). Abstract Thumb hypoplasia is a congenital underdevelopment of the thumb, accounting for 5%–15% of congenital hand disorders. It occurs equally among both genders and can affect both thumbs. The condition is categorized using Blauth's classification with Type I being the mildest form. We report a 23‐year‐old Syrian male presented with a bilateral restriction in opposition movement when using a pen or razor. Clinical examination and x‐ray imaging revealed a bilateral Type I hypoplastic thumb with bilateral minimal hypoplasia of the toes. Despite the surgical treatment options available, the patient opted not to undergo surgery due to his adaptation to his condition. Hypoplastic thumb Type I is a congenital condition characterized by underdevelopment of the thumb. Bilateral thumb hypoplasia with toes hypoplasia is extremely rare. A full systemic evaluation should be done due to its associations with other syndromic manifestations and treatment options are discussed concerning the best functional outcomes and patient preferences.

Key clinical Message This case highlights the significance of maintaining clinical suspicion for CPBs in adults presenting with SBO. Early surgical intervention, offering both diagnosis and treatment, is essential for managing this rare cause of SBO. Increased clinical awareness of CPBs will help ensure they are considered in the differential diagnosis of adult patients with bowel obstruction.

This research work deals with the examination of the techno-economic, exergy, and energy analyses of biomass gasification of the invasive weed Parthenium hysterophorus (PHP) using Steam - Carbon dioxide (CO2) as a gasifying agent with the support of simulation modeling for sustainable energy conversion process. The aim of this work is to simulate the gasification process through consideration of the impacts of various operating factors on gasification. This study attains the gradual increase in hydrogen (H2) concentration from 51% to 63% along with the rise in carbon monoxide (CO) from 14.5% to 19% using Aspen Plus simulation. CO2 falls concurrently from 24% to 13.5%. The findings demonstrate significant advancements over earlier studies in terms of both gas composition and overall system performance. A computational model has been developed for the estimation of energy performance indicators such as total energy input, and energy consumed per mass of biomass gasified, which are used in the determination of the system's energy efficiency. The exergy analysis of the system is performed to assess the system's total losses in terms of efficiency gathered from the system's exergy ratios. The economic analysis evaluates the system's economies of scale by gas production at ₹.15/kg and long-term sustainability. The proposed system has been found with the potential to produce a high yield of alternative energy from PHP with increased economic efficiency and lower environmental impact.

The Trichilia emetica plant is traditionally used for medicinal and food purposes. However, there are limited studies on the bioactivity and cytotoxicity of its seed butter and aril oil. This study aimed to assess the antidiabetic activity and cytotoxicity of seed butter and aril oil, obtained via two different extraction methods, and compare their lipid profiles. The plant samples were collected from the Faifa mountains and extracted using a Soxhlet apparatus for hot extraction and a magnetic stirrer for cold maceration. The antidiabetic activity and cytotoxicity were evaluated using the α-amylase and MTT assays, respectively. The fatty acids were quantified utilizing gas chromatography-mass spectrometry. This study proves the impact of the extraction method on the yield, cytotoxicity, antidiabetic activity and lipid profile. The highest cytotoxicity was observed with the seed butter obtained via Soxhlet extraction. The α-amylase inhibition was observed at the highest levels with the seed butter and aril oil obtained via cold maceration. The palmitic acid (PA) and oleic acid (OA) were detected at their maximal concentrations in the seed butter obtained via Soxhlet extraction and aril oil obtained via cold maceration, respectively. This study represents an essential basis for understanding the importance of T. emetica as a valuable tree for food, cosmetic and medicinal purposes. Further experiments can lead to the development of green extraction techniques and isolation of the cytotoxic and antidiabetic molecules that can be developed into new pharmaceutical products or serve as lead molecules for new drugs.

The purpose of this paper is to understand perceptions of interior design students after using game-based learning (GBL) as an approach to address workload distribution, lack of clear assessment criteria, and deficiencies of the master-apprentice model during the process of solving several small-scale design problems along the course of a semester. A literature review of the instructional issues in design studios is presented along with an overview of the activity systems theory as an underpinning theoretical perspective. This research paper explains the research design behind the case study methodology used to perform data collection, analysis measures and organize coding schemes. Findings from the study conclude that GBL fits into the iterative and experimental nature of the design process, helps students focus on the design process through trial and error without a significant risk, changes the studio's feedback structure, and allows students to track their progress while having creative freedom. This paper provides empirical evidence supporting the existence of instructional issues in traditional design studios, provides considerations for using GBL to address these issues, and suggests directions for future research studies in fields of instructional technology, design pedagogy and higher education policy.

Background: Solanum pseudocapsicum (PC) and Capsicum annum (CA) belongs to the family of Solanaceae. CA have been reported a rich source of phenolics whereas, the phenolics content of GA (gallic acid), SC (scopoletin), RA (rosmarinic acid), and RV (resveratrol) are yet to be reported for the PC-fruit. This study comparatively evaluates the phenolics profile for different parts (seeds and skin) and colors (green and red) of the PC- and CA-fruits using the green solvents of ethanol (ET), acetone (AC), water (H2O), and different combinations of these solvents. Methodology: Ultrasonics extraction (US) and UHPLC analysis were employed for phenolics evaluation. Results: The USMD (method development) revealed the highest extract yield of 62 mg/100 mg for the PC-skin in ET:AC (70:30) solvent whereas, more phenolics (ppm) were observed for PC-seeds in ET:AC (50:50) solvent, particularly the SC (29.46) and GA (16.92). The UHPLCMDMV exhibited significant accuracies (100.70–114.14 %) with r2-values (0.9993–0.9997) in the linearity range of 1–200 ppm. The USMV (method validation) in PC- and CA-fruit parts and colors revealed more extract yields for the red skin part of the PC- (180.5 mg) and CA-fruit (126.2 mg). The phenolics were seen more in the green seeds of the PC-fruit (ppm); SC (276), GA (147.36), RV (28.54), and RA (23.87) followed by the green PC-skin, and red/green CA-seeds. The statistical models of mean differences, ANOVA, and Pearson’s correlation showed significant differences for the PC-fruit parts (seeds and skin) and colors (red and green) vs extract yield and phenolics content (P = 0.05). Conclusion: PC-and CA-fruits were successfully evaluated where the seeds for the green fruits exhibited more phenolics amount.

The objective of this paper is to study and define some algebraic curves with neutrosophic variables in neutrosophic real field 𝑅(𝐼), where we study what are the relationships between classical algebraic curves and neutrosophic algebraic curves depending on the geometric isometry (AH-Isometry).