Early detection of pancreatic cancer in the era of precision medicine.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality and it is often diagnosed at advanced stages due to non-specific clinical presentation. Disease detection at localized disease stage followed by surgical resection remains the only potentially curative treatment. In this era of precision medicine, a multifaceted approach to early detection of PDAC includes targeted screening in high-risk populations, serum biomarkers and "liquid biopsies", and artificial intelligence augmented tumor detection from radiologic examinations. In this review, we will review these emerging techniques in the early detection of PDAC.

Decompression Alone vs Decompression and Fusion: Spin in Abstracts of Systematic Reviews and Meta-Analysis.

STUDY DESIGN: Cross-sectional. OBJECTIVES: Spin, a prevalent bias, can distort outcomes in well-validated research. Treatment of lumbar stenosis with spondylolisthesis through decompression alone (DA) vs decompression and fusion (DF) remains a controversial topic. We aimed to identify the prevalence of spin in meta-analyses and systematic reviews regarding DA vs DF in the treatment of spinal stenosis with concomitant degenerative spondylolisthesis. METHODS: MEDLINE, Web of Science, and Google Scholar were searched for meta-analyses and systematic reviews comparing DA vs DF treatment of lumbar spinal stenosis accompanied by degenerative spondylolisthesis. Each study was evaluated for the nine most severe spin types. We also explored the association between spin and methodological quality of a systematic review using the revised A Measurement Tool to Assess Systematic Reviews appraisal tool. RESULTS: The search yielded 1506 articles, of which 13 met inclusion. It was found that 46.2% (6/13) of the articles contained spin within the abstract. Of the nine most severe types, type 5 was found to be the most prevalent (4/13, 30.8%), followed by types 9 (2/13, 15.4%), 3 (1/13, 7.7%), 4 (1/13, 7.7%), and 6 (1/13, 7.7%). Spin types 1, 2, 7 and 8 were not found. According to AMSTAR-2, 53.8% (7/13) of the studies were appraised as "critically low" quality and 46.2% (6/13) as "low" quality. CONCLUSION: This study demonstrated the presence of spin in 46.2% of abstracts pertaining to the treatment for spinal stenosis with degenerative spondylolisthesis. Spine surgeons should learn to recognize spin as they review articles before implementing them into practice.

Cinematic rendering of primary adrenal lymphoma.

Primary adrenal lymphoma (PAL) is a particularly rare subset of malignant adrenal neoplasms, accounting for ∼1% of all non-Hodgkin's lymphomas. Reported outcomes of PAL, though limited, are dismal, with a 12-month survival rate of ∼20%. PAL is treated with polychemotherapy and early tissue diagnosis to allow initiation of chemotherapy is associated with improved outcomes. Early and accurate radiological diagnosis of PAL is therefore essential in improving outcomes through informing decisions to biopsy and thereby facilitating timely initiation of chemotherapy. To date, however, imaging features of PAL have not been conclusively defined, and a range of divergent imaging appearances have been reported. Cinematic rendering (CR) is a 3D post-processing technique that simulates the propagation and interaction of photons as they pass through the imaged volume. This results in the generation of more photorealistic images that may allow for more comprehensive visualization, description and interpretation of anatomical structures. This manuscript presents the first characterization of the various CR appearances of PAL in the reported literature and provides commentary on the clinical opportunities afforded by CR in the workup of these heterogenous tumors.

Hidden in plain sight: commonly missed early signs of pancreatic cancer on CT.

Pancreatic ductal adenocarcinoma (PDAC) has poor prognosis mostly due to the advanced stage at which disease is diagnosed. Early detection of disease at a resectable stage is, therefore, critical for improving outcomes of patients. Prior studies have demonstrated that pancreatic abnormalities may be detected on CT in up to 38% of CT studies 5 years before clinical diagnosis of PDAC. In this review, we highlight commonly missed signs of early PDAC on CT. Broadly, these commonly missed signs consist of small isoattenuating PDAC without contour deformity, isolated pancreatic duct dilatation and cutoff, focal pancreatic enhancement and focal parenchymal atrophy, pancreatitis with underlying PDAC, and vascular encasement. Through providing commentary on demonstrative examples of these signs, we demonstrate how to reduce the risk of missing or misinterpreting radiological features of early PDAC.

Comparative analysis of oral and local intraovarian administration of metformin and nanoparticles (NPs11) in alleviating testosterone-induced polycystic ovary syndrome in rats.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic dysfunction. This study aims to compare the oral and local treatments of metformin or its nanoparticles (NPs11) for ameliorating PCOS in rats. Rats were divided into 4 groups: the control group with no drug treatment; the PCOS group, where subcutaneous testosterone was given (10 mg/kg/day) for 28 days; the MET group, where metformin was administered orally or locally; and the NP group, where metformin NPs11 were also administered orally or locally. Oral administrations were for 21 days, while local injection was performed once surgically. After 7 weeks, all rats were sacrificed; blood glucose and serum hormonal levels and lipid profile were estimated, and the ovaries were assessed by histopathological, Ki-67 immunohistochemical, and histomorphometric evaluations. Blood glucose levels were significantly decreased in groups of orally administered metformin or NPs11 only, while the most efficient option for modulating PCOS-induced hormonal and lipid profile changes was intraovarian injection of NPs11. The ovaries of PCOS rats demonstrated large follicular cysts, massive collagen depositions, and attenuated Ki-67 immunoexpression. Also, the PCOS group revealed a significant decrease in the count of all stages of growing follicles, corpora lutea, granulosa cell layer thickness, and surface area of corpora lutea, in addition to an increase in the number of atretic follicles and follicular cysts, theca cell layer thickness, and surface area of the follicular cysts. All these parameters were recovered with metformin or their NPs11 treatments in different degrees, while local injection of NPs11 was the best option.

Machine learning assisted methods for the identification of low toxicity inhibitors of Enoyl-Acyl Carrier Protein Reductase (InhA).

Tuberculosis (TB) is one of the life-threatening infectious diseases with prehistoric origins and occurs in almost all habitable parts of the world. TB mainly affects the lungs, and its etiological agent is Mycobacterium tuberculosis (Mtb). In 2022, more than 10 million people were infected worldwide, and 1.3 million were children. The current study considered the in-silico and machine learning (ML) approaches to explore the potential anti-TB molecules from the SelleckChem database against Enoyl-Acyl Carrier Protein Reductase (InhA). Initially, the entire database of ∼ 119000 molecules was sorted out through drug-likeness. Further, the molecular docking study was conducted to reduce the chemical space. The standard TB drug molecule's binding energy was considered a threshold, and molecules found with lower affinity were removed for further analyses. Finally, the molecules were checked for the pharmacokinetic and toxicity studies, and compounds found to have acceptable pharmacokinetic parameters and were non-toxic were considered as final promising molecules for InhA. The above approach further evaluated five molecules for ML-based toxicity and synthetic accessibility assessment. Not a single molecule was found toxic and each of them was revealed as easy to synthesise. The complex between InhA and proposed and standard molecules was considered for molecular dynamics simulation. Several statistical parameters showed the stability between InhA and the proposed molecule. The high binding affinity was also found for each of the molecules towards InhA using the MM-GBSA approach. Hence, the above approaches and findings exposed the potentiality of the proposed molecules against InhA.

Cinematic Rendering of Pancreatic Neuroendocrine Tumours: Opportunities for Clinical Implementation: Part 1: Tumour Detection and Characterization.

Pancreatic neuroendocrine tumours (PNETs) are a rare subset of pancreatic tumours that have historically comprised up to 3% of all clinically detected pancreatic tumours. In recent decades, however, advancements in imaging have led to an increased incidental detection rate of PNETs and imaging has played an increasingly central role in the initial diagnostics and surgical planning of these tumours. Cinematic rendering (CR) is a 3D post-processing technique that generates highly photorealistic images through more realistically modelling the path of photons through the imaged volume. This allows for more comprehensive visualization, description, and interpretation of anatomical structures. In this 2-part review article, we present the first description of the various CR appearances of PNETs in the reported literature while providing commentary on the unique clinical opportunities afforded by the adjunctive utilization of CR in the workup of these rare tumours. The first of these 2 instalments highlights the utility of CR in optimizing PNET detection and characterization.

Synthesized PANI/CeO2 Nanocomposite Films for Enhanced Anti-Corrosion Performance.

This study introduces a novel nanocomposite coating composed of PANI/CeO2 nanocomposite films, aimed at addressing corrosion protection needs. Analysis through FTIR spectra and XRD patterns confirms the successful formation of the nanocomposite films. Notably, the PANI/CeO2 nanocomposite films exhibit a hydrophilic nature. The bandgap energy of the PANI composite film is measured to be 3.74 eV, while the introduction of CeO2 NPs into the PANI matrix reduces the bandgap energy to 3.67 eV. Furthermore, the electrical conductivity of the PANI composite film is observed to be 0.40 S·cm-1, with the incorporation of CeO2 NPs leading to an increase in electrical conductivity to 1.07 S·cm-1. To evaluate its efficacy, electrochemical measurements were conducted to assess the corrosion protection performance. Results indicate a high protection efficiency of 92.25% for the PANI/CeO2 nanocomposite film.

Cinematic Rendering of Pancreatic Neuroendocrine Tumours: Opportunities for Clinical Implementation: Part 2: Preoperative Planning and Evaluation of Metastatic Disease.

Pancreatic neuroendocrine tumours (PNETs) are a rare subset of pancreatic tumours that have historically comprised up to 3% of all clinically detected pancreatic tumours. In recent decades, however, advancements in imaging have led to an increased incidental detection rate of PNETs and imaging has played an increasingly central role in the initial diagnostics and surgical planning of these tumours. Cinematic rendering (CR) is a 3D post-processing technique that generates highly photorealistic images through more realistically modelling the path of photons through the imaged volume. This allows for more comprehensive visualization, description, and interpretation of anatomical structures. In this 2-part review article, we present the first description of the various CR appearances of PNETs in the reported literature while providing commentary on the unique clinical opportunities afforded by the adjunctive utilization of CR in the workup of these rare tumours. This second instalment focuses on the applications of CR in optimizing preoperative planning of PNETs.

Investigating the Promising Anticancer Activity of Cetuximab and Fenbendazole Combination as Dual CBS and VEGFR-2 Inhibitors and Endowed with Apoptotic Potential.

In this work, the cytotoxicity of monoclonal antibody (Cetuximab, Ce) and Fenbendazole (Fen), as well as their combination therapy were tested with the MTT assay. On the other side, Ce, Fen, and a combination between them were subjected to a colchicine-tubulin binding test, which was conducted and compared to Colchicine as a reference standard. Besides, Ce, Fen, and the combination of them were tested against the VEGFR-2 target receptor, compared to Sorafenib as the standard medication. Moreover, the qRT-PCR technique was used to investigate the levels of apoptotic genes (p53 and Bax) and anti-apoptotic gene (Bcl-2) as well. Also, the effect of Ce, Fen, and the combination of them on the level of ROS was studied. Furthermore, the cell cycle analysis and Annexin V apoptosis assay were carried out for Ce, Fen, and a combination of them. In addition, the molecular docking studies were used to describe the molecular levels of interactions for both (Fen and colchicine) or (Fen and sorafenib) within the binding pockets of the colchicine binding site (CBS) and vascular endothelial growth factor-2 receptor (VEGFR-2), respectively.

Impact of COVID-19 on the use of online mental health services among adults in Riyadh: a cross-sectional study.

OBJECTIVE: Online therapies are licensed online programs designed to aid the use of psychotherapy via the Internet or mobile phone applications by providing effective treatments through digital communication. The number of individuals seeking online therapy has increased during the COVID-19 pandemic. Thus, this study aimed to assess the impact of COVID-19 on the use of online mental health services among Saudi adults in Riyadh. SUBJECTS AND METHODS: The research design was a cross-sectional descriptive study. The data collection tool was an online survey distributed through social media and email. The survey consisted of two parts: a sociodemographic questionnaire and the e-Therapy Attitudes and Process (eTAP). A total of four hundred participants have completed the survey. RESULTS: Most of the respondents had used online therapy for the first time during the COVID-19 pandemic, and most of the users had a relatively positive experience with online interventions for mental health services. CONCLUSIONS: The findings showed that COVID-19 had an impact on the use of online therapy, as it caused an increase in the number of users of these services, and most of the users have found online therapy to be helpful.

The long-term consequences of the hypospadias salvage repair issue.

PURPOSE: To present the long-term results of redo-hypospadias at our tertiary referral center following a failed prior repair. METHODS: One hundred sixty-four individuals with a history of unsuccessful repairs qualified for our retrospective cohort study. Our inclusion criteria were as follows: pre-operative data that was accessible, redo-hypospadias that was successfully repaired, and at least three years of follow-up at the last hospital visit. RESULTS: The mean patient age was 91.3 ± 21.1 months. The mean follow-up after successful repair was 41.3 ± 3.1 months. Ninety-two (group A) had one prior repair, and 72 (group B) had 2 or 3 repairs. Group A underwent six primary techniques: 32 underwent Onlay Island Flap (OIF), 10 underwent Mathieu, 12 underwent Tubularized Incised Plate Urethroplasty (TIPU), 8 underwent Urethral Mobilization (UM), and 34 underwent Buccal Mucosal Graft (BMG) { dorsal inlay Graft Urethroplasty (DIGU) in 4 and staged BMG in 30 patients}. In group B, four procedures were used: TIPU in 4, UM in 6, and BMG in 62 (staged BMG in 50 cases and DIGU in 12). CONCLUSIONS: The selected type of repair will depend on many factors, like residual healthy local skin and expertise. Safe techniques for repair of redo hypospadias after its 1st failure include TIPU, Mathieu, UM, OIF, and DIGU for distal varieties. After 2nd or 3rd repair DIGU, UM, and TIPU can be performed in distal types, while staged BMG can be applied for proximal ones.

Utilisation of specialist epilepsy services and antiseizure medication adherence rates in a cohort of people with epilepsy (PWE) accessing emergency care.

BACKGROUND: An epilepsy-related attendance at A&E is associated an increased risk of subsequent death within 6 months. Although further work is required to provide a definitive explanation to account for these findings, in the interim it would seem reasonable that services are designed to ensure timely access and provide support at a time of greatest risk. We aim to determine the frequency of patients accessing specialist neurology services following an epilepsy-related admission/unscheduled care episode and consider ASM adherence at the point of attendance. METHODS: Patients were identified retrospectively via the NHS Greater Glasgow and Clyde live integrated epilepsy Dashboard following an unscheduled epilepsy-related admission or A&E attendance between 1st January 2022 and 30th June 2022. We calculated adherence to anti-seizure medication for a period of 6 months prior to admission and defined poor medication adherence as a medication possession ratio of less than 80 %. We evaluated the rate of any outpatient neurology clinic attendance in the subsequent 3, 6 and 12 months following an epilepsy-related unscheduled care episode. Additional clinical information was identified via the electronic patient records. RESULTS: Between 1st Jan 2022 and 30th June 2022, there were 266 emergency care seizure-related attendances. The mean age at attendance was 46 years (range: 16-91). Most of PWE were males (63 %) and 37 % were females. Epilepsy classification-29.3 % had GGE, 41.7% had focal epilepsy, and in 29 % of cases the epilepsy was unclassified. Of the admissions, 107/ 266 (40.2 %) generated follow-up within 6 months of attendance. Poor medication adherence was noted in 54/266 (20.3 %). 28.2 % of cases had input from on-call neurology service during admission/ED attendance, and of those 60 % had ASM adjusted. 18 % of attendances had a background diagnosis of learning disability. One-third of attendances of PWE had a history of mental health disorder 35 % (93/266). 25 % of ED attendances noted an active history of alcohol consumption misuse or/and recreational drug use. 14 (5.5 %) of PWE died during the period of interest (12 months following the last ED visit). In 6/14 (42.3 %) death was associated with poor medication adherence. CONCLUSION: This study demonstrates that a significant proportion of patients who experienced seizure-related admissions/ attendance did not access specialist neurology services in a timely manner. In addition, poor medication adherence remains a problem for a substantial number of people living with epilepsy. Early access to specialist services may go some way to improving care and reducing excessive mortality in PWE by allowing anti-seizure medication to be titrated and poor medication adherence to be addressed in those at greatest risk.

Three-dimensional CT cinematic rendering of adrenal masses: Role in tumor analysis and management.

The adrenal gland is home to an array of complex physiological and neoplastic disease processes. While dedicated adrenal computed tomography (CT) is the gold standard imaging modality for adrenal lesions, there exists significant overlap among imaging features of adrenal pathology. This can often make radiological diagnosis and subsequent determination of the optimal surgical approach challenging. Cinematic rendering (CR) is a novel CT post-processing technique that utilizes advanced light modeling to generate highly photorealistic anatomic visualization. This generates unique prospects in the evaluation of adrenal masses. As one of the first large tertiary care centers to incorporate CR into routine diagnostic workup, our preliminary experience with using CR has been positive, and we have found CR to be a valuable adjunct during surgical planning. Herein, we highlight the unique utility of CR techniques in the workup of adrenal lesions and provide commentary on the opportunities and obstacles associated with the application of this novel display method in this setting.

Cinematic rendering of solid pseudopapillary tumors: Augmenting diagnostics of an increasingly encountered tumor.

Pancreatic solid pseudopapillary tumors (SPTs) are a rare subset of pancreatic neoplasms, accounting for under 2 % of exocrine pancreatic tumors. The incidence of SPTs has shown a significant increase in the past two decades, attributed to heightened cross-sectional imaging utilization. These tumors often present with nonspecific clinical symptoms, making imaging a crucial tool in their detection and diagnosis. Cinematic rendering (CR) is an advanced 3D post-processing technique that generates highly photorealistic realistic images by accurately modeling the interaction of light within the imaged volume. This allows improved visualization of anatomic structures which holds potential to improve diagnostics. In this manuscript we present the first description of CR appearances of SPTs in the reported literature. Through showcasing a range of cases, we highlight the potential of CR in illustrating the diverse imaging characteristics of these unique neoplasms.

CT angiography for characterization of advanced placenta accreta spectrum: indications, risks, and benefits.

Placenta accreta spectrum disorder (PASD) encompasses various types of abnormal placentation in which chorionic villi directly adhere to or invade the myometrium. The incidence of PASD has dramatically risen in the US over the past 3 decades owing to the increased rates of patients undergoing cesarean sections. While PASD remains a significant cause of maternal morbidity and mortality, accurate prenatal identification and characterization of PASD is associated with improved outcomes. Although ultrasound is the first-line imaging modality in the evaluation of PASD, with MRI serving as an adjunct, computed tomography angiography (CTA) may also offer unique diagnostic advantages in cases of advanced PASD by providing superior visualization of placental and abdominopelvic vasculature and enabling the creation of comprehensive vascular maps to roadmap complex surgical interventions. This paper represents the first evaluation of CTA as a diagnostic tool and operative planning aid in this context. Appropriate indications and diagnostic advantages of CTA in this setting are reviewed, and key multimodal imaging features of normal and abnormal placentation are highlighted.

A Comparative Analysis of Marginal Adaptation Values between Lithium Disilicate Glass Ceramics and Zirconia-Reinforced Lithium Silicate Endocrowns: A Systematic Review of In Vitro Studies.

This systematic review aimed to identify and analyze in vitro studies on the marginal adaptation values of computer-aided-design/computer-aided-manufacturing (CAD/CAM) and heat-pressed lithium disilicate glass ceramics and zirconia-reinforced lithium silicates and endocrown restorations. A full literature search was conducted in Web of Science, PubMed/Medline, EMBASE, Scopus, Cochrane Library, Google Scholar, and ProQuest electronic databases. The following keywords: endocrown [(marginal adaption) or (marginal fit) or internal fitting)], endocrown [(molar(s)) or (premolar(s) or (posterior teeth) or (maxillary arch) or (mandibular arch)] and ceramic materials as [(lithium disilicate glass ceramic CAD/CAM) or (zirconia) or (heat-press)] were used. Articles were manually searched utilizing their reference lists. Study selection was restricted or limited to the time of publication but not to the type of tested teeth or ceramic material, endocrown design, system of endocrown construction, abutment scanning, and system of the marginal adaption measurement. A total of 17 in vitro studies published between 2016 and 2023 were included in this systemic review. Less than half of the studies were published during 2023. Most studies used lithium disilicate glass ceramic and zirconia-reinforced lithium silicate all-ceramic materials by CAD/CAM or heat-press systems. Marginal adaptation, or marginal gap, was almost equal in the 2 materials, while it was slightly or marginally higher in the heat-press than in the CAD/CAM system. All-ceramic lithium disilicate glass ceramic and/or zirconia endocrowns fabricated for posterior teeth in both arches using CAD/CAM or heat-press had recorded marginal adaptation values within an acceptable range.

Synthesis, X-ray crystallography and antimicrobial activity of 2-cyanoguanidinophenytoin.

The optimized synthesis of [5-oxo-4,4-diphenylimidazolidin-2-ylidene]cyanamide, which is known as 2-cyanoguanidinophenytoin (CNG-DPH) (3), and (imidazo[4,5-d]imidazole-2,5-diylidine)dicyanamide (4) has been reported in the present work. Furthermore, new Mannich bases derived from CNG-DPH were synthesized via its reaction with formaldehyde and using the corresponding amines, piperidine (base 5), and morpholine (base 6). Also, the antimicrobial activity and X-ray crystal structures for CNG-DPH and their Mannich bases were studied. The bases 3 and 6 crystallized in a monoclinic system; the crystal structure of 3 containing four molecules in the unit cell with a P21/c space group. The unit cell of 6 has eight molecules with a C2/c space group. The inter and intra hydrogen bond contacts packed and stabilized both of the structures. The morpholine ring of base 6 demonstrated a distinctive chair configuration. Mannich bases 5 and 6 showed promising antimicrobial effects. base 4 has a greater percentage for in vitro cytotoxicity (IC50) against normal cells, whereas 3 has the lowest ratio.