Benign Conditions Research Articles

Energy-saving and benign hydrogen production by coal gasification fine slag-assisted Water electrolysis

ABSTRACT Integrating anodic coal gasification fine slag oxidation with cathodic hydrogen evolution reaction presents an environmentally friendly and energy-efficient solution for solid waste recycling and hydrogen production. This innovative approach exhibits higher activity and stability than conventional water electrolysis, while also preventing anode degradation due to its benign reaction conditions. The kinetic investigations have revealed that slag oxidation occurs more rapidly than water oxidation. Specifically, slag undergoes direct and indirect oxidation within the potential regions below and above those of water oxidation, respectively. This study has the potential to shed light on the mechanisms underlying slag electrolysis and offer valuable insights for the simultaneous recycling of solid waste and hydrogen production.

The outcomes of parathyroid gland autotransplantation during thyroid surgery: a systematic review, meta-analysis and trial sequential analysis.

Thyroidectomy is the treatment of choice for malignant thyroid diseases as well as for benign conditions who cannot be treated medically. The most common complication following thyroidectomy is hypocalcaemia and hypoparathyroidism that usually results from accidental damage or removal of one or more parathyroid glands. Parathyroid gland autotransplantation has been one of the most common intraoperative strategies applied to tackle this problem. The aim of this study is to assess whether parathyroid auto trasnplantation is associated with a decrease in postoperative hypoparathyroidism following thyroidectomy. We conducted a thorough systematic review and meta-analysis of relevant studies published up to February 2024 in MEDLINE, Scopus, Embase and Cochrane Library databases. We compared the incidence of postoperative hypoparathyroidism between the group of patients who underwent autotransplantation and the patients were the parathyroid glands were preserved in situ. A trial sequential analysis was performed subsequently to confirm the findings. Eighteen studies fulfilled all the inclusion criteria and were ultimately included in our study. The total number of patients was 8,182 with 4,029 receiving parathyroid gland autotransplantation. Autotransplantation was associated with a higher incidence of immediate (within 24 h) and transient hypoparathyroidism (RR 1.58, 1.45-1.73, CI 95%, p < 0.00 and RR 1.60, 1.47-1.76, CI 95%, p < 0.001, respectively). However, it did not affect the rate of permanent postoperative hypoparathyroidism (RR 0.85, 0.51-1.41, CI 95%, p = 0.54). The subsequent trial sequential analysis confirmed these findings. Parathyroid autotransplantation does not lead to a decrease in the rate of permanent post-thyroidectomy hypoparathyroidism. The most important factor to decrease its incidence remains the accurate identification and preservation of the parathyroid glands intraoperatively.

Comparative analysis between outcomes of minimally invasive gynaecological surgeries and traditional abdominal surgeries for benign gynaecological conditions.

To compare outcomes of minimally invasive gynaecological surgeries with open gynaecological surgical techniques in a low-resource setting. The quasi-experimental study was conducted at a tertiary care public-sector hospital in Rawalpindi, Pakistan, from September 2022 to August 2023, and comprised women with benign gynaecological conditions. The subjects were divided into two groups. Group-I included participants who underwent minimally invasive gynaecological surgeries, while Group- II patients underwent open gynaecological surgical intervention. Outcome variables included pre-discharge pain score, post-operative mobility, operative time, blood-loss during surgery, length of hospital stay and intraoperative as well as postoperative complications. Data was analysed using SPSS 25. Of the 319 women, 146(45.7%) were in Group-I with mean age 30.83±5.47 years, and 173(54.2%) were in group-II with mean age 44.87±10.46 years. Body mass index, length of marriage, history of previous surgery, comorbidities and menopausal status were significantly different between the groups (p<0.05). Duration of surgery and hospital stay were lower in Group-I compared to Group-II (p<0.05). Intra-operative complications were not significantly different between the groups (p<0.05), while the differences in post-operative complications were significant (p<0.05). Better clinical outcomes were observed for minimally invasive gynaecological surgeries than open surgeries among women diagnosed with benign gynaecological diseases.

Accessing Active Fragments for Drug Discovery Utilising Nitroreductase Biocatalysis.

Biocatalysis has played a limited role in the early stages of drug discovery. This is often attributed to the limited substrate scope of enzymes not affording access to vast areas of novel chemical space. Here, we have shown a promiscuous nitroreductase enzyme (NR-55) can be used to produce a panel of functionalised anilines from a diverse panel of aryl nitro starting materials. After screening on analytical scale, we show that sixteen substrates could be scaled to 1 mmol scale, with several poly-functional anilines afforded with ease under the standard conditions. The aniline products were also screened for activity against several cell lines of interest, with modest activity observed for one compound. This study demonstrates the potential for nitroreductase biocatalysis to provide access to functional fragments under benign conditions.

Harnessing palladium-decorated g-C3N4 nanosheets for selective catalytic benzyl alcohol synthesis

The selective reduction of benzaldehyde to benzyl alcohol (a pivotal model reaction for the low-temperature stabilization of bio-oil) was meticulously investigated. This study delved into the catalytic prowess of Pd-modified g-C3N4 nanosheets (PdxCN) within a liquid-phase environment, utilizing H2 as the reducing agent under benign conditions. A series of photocatalysts were synthesized by impregnating graphitic carbon nitride nanosheets (NS-CN) with varying weight percent loadings of Pd nanoparticles. In the context of this selective hydrogenation, the catalytic activity of Pd2CN catalysts outshone that of pure NS-CN and other reference catalysts, exhibiting remarkable efficacy with benzyl alcohol yields nearing perfection at approximately 99%. Moreover, these catalysts demonstrated enduring catalytic reusability and reproducibility. The optimization of experimental parameters, encompassing weight percent loading of co-catalyst, catalyst quantity, temperature, and reaction duration, was systematically undertaken to achieve optimal benzyl alcohol yield.

Sleep, cognitive functions, behavioral, and emotional disturbance in self-limited focal childhood epilepsies

BackgroundSelf-limited focal epilepsies of childhood, including self-limited epilepsy with centrotemporal spikes (SeLECTS), idiopathic childhood occipital epilepsy of Gastaut (ICOE-G), and self-limited epilepsy with autonomic seizures (SeLEAS), were considered benign conditions. However, recent research assumed potential adverse impacts on sleep, cognition, behavior, and emotional well-being. Our aim was to investigate the effects of self-limited focal epilepsies on sleep architecture, cognitive functions, behavior, and emotional disturbances in drug naive children. A cross-sectional study was conducted on 46 newly diagnosed children (ages 6–12) with SeLECTS (n = 22), ICOE-G (n = 12), SeLEAS (n = 12), and 20 healthy controls. Overnight polysomnography was performed. Cognitive assessments included intelligence scales, executive function tests, verbal fluency, visuospatial abilities, and memory. Behavioral and emotional problems were evaluated using standardized questionnaires and psychiatric interviews.ResultsChildren with epilepsy exhibited significant disturbances in sleep architecture, impairments in cognitive domains (executive functions, verbal fluency, visuospatial skills, and memory), and higher rates of internalizing/externalizing problems, social issues, attention deficit hyperactive disorder, depression, and anxiety compared to controls. No significant differences were found among the three epilepsy subtypes.ConclusionSelf-limited focal epilepsies in childhood are associated with sleep disruption, cognitive deficits, behavioral issues, and psychiatric comorbidities, challenging their traditional "benign" perception. Comprehensive management approaches addressing these multidimensional impacts are warranted.

Initiation of Haploidentical Stem Cell Transplantation With Post-Transplant Cyclophosphamide in Children: A Low-Middle-Income Country Institutional Experience.

Haploidentical hematopoietic stem cell transplant (HSCT) is a curative treatment especially for countries where bone marrow registries are nonexistent. We present our experience with haploidentical HSCT in pediatric patients. Retrospective data collected and analyzed for patients ≤18 years, from January 2017 to December 2022. The cohort consisted of 20 patients with median age at transplant of 61.5 (IQR: 124) months. Fourteen (70%) were malignant and 6 (30%) were benign diseases. Donors were father in majority (9/20; 45%). Stem cell source was peripheral blood 8, marrow 8, and combined 4. c-specific antibodies were positive in 6 (30%). Median CD34 cell dose infused: 9.35 × 106/kg. Median engraftment time: 15 (IQR: 17) days. Acute and chronic graft-versus-host disease (GVHD) occurred in 12/20 (60%) and 5/20 (25%), respectively. Complications included infection/sepsis (14/20; 70%), cytomegalovirus reactivation (14/20; 70%), sinusoidal obstruction syndrome (1/20; 5%), primary graft failure (PGF) (6/20; 30%), and secondary graft failure (4/20; 20%). PGF was more common in benign conditions (p = 0.003) and less prevalent in cases with aGVHD (p = 0.007). aGVHD was more common in malignant conditions (p = 0.007). Overall survival (OS), relapse-free survival (RFS), and treatment-related mortality (TRM) were 40%, 50%, and 35%, respectively. Median time of survival and relapse were 8 (IQR: 15) and 9 (IQR: 13) months, respectively. OS was comparable to that of other low-middle-income countries. GVHD was a major challenge, along with sepsis and CMV infection. Half of the leukemias relapsed. Graft failure was a major concern in nonmalignant diseases.

Zosteriform Cutaneous Metastasis from Breast Cancer: A Case Report

Introduction: Cutaneous metastases are observed in approximately 10% of oncology patients, often indicating either a persistent solid tumor or the recurrence of neoplastic disease. The most prevalent cause of cutaneous metastases in females is breast cancer. Patients with breast cancer may exhibit cutaneous manifestations at the initial diagnosis; however, these metastases more frequently emerge well after the initial diagnosis and treatment. The cutaneous lesions resulting from metastatic breast carcinoma display considerable variability in appearance. Typically, they manifest as firm, flesh-colored to red, smooth or ulcerated, or crusted nodules, papules, and plaques on the ipsilateral chest wall and breast. Additionally, unusual sites for breast cancer cutaneous metastases include the eyelids, inframammary folds, ipsilateral lymphedematous arm, scalp, subungual nail bed, and umbilicus. Skin metastases can also occur in mastectomy scars and radiation therapy ports. Several distinct patterns of skin metastases are recognized in breast cancer patients: carcinoma erysipelatoides, carcinoma telangiectoides, and carcinoma encuirasse. Recently, carcinoma hemorrhagiectoides has also been documented. The pleomorphic nature of breast cancer metastases can mimic various benign and malignant conditions, such as collision tumors, cysts, dermatofibromas, milia-en-plaque, melanoma, non-melanoma skin cancers, cellulitis, folliculitis, herpes zoster, paronychia, erythema annulare centrifugum, urticaria, alopecia areata, dermatitis, hidradenitis suppurativa, scleroderma, angiokeratoma, angiosarcoma, lymphangioma circumscriptum, purpura, and pyogenic granuloma. Consequently, it is crucial to consider the possibility of cutaneous metastasis from breast cancer in any patient, whether previously diagnosed with breast cancer or not, who presents with new or treatment-resistant cutaneous lesions. Confirmation of the diagnosis necessitates a biopsy of the skin lesion. ...........

Changes in analgesic prescriptions in Dutch general practice

Background Increases in opioid prescriptions have been described; however, recent trends and prescribing patterns of analgesics in Dutch general practice are largely unknown. Objective To investigate recent changes in the number of analgesic prescriptions, and the indications for prescribing strong opioids. Furthermore, we aim to identify risk factors for chronic opioid use in Dutch general practice. Design and setting A retrospective cohort study from 1 July 2013 to 31 June 2022, using a primary care practice based research network. Subjects Patients with ≥1 prescription for analgesics during the study period were included. Main outcome measure Changes in the number of prescriptions for paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in Dutch general practice during the 9-year study period. Moreover, we analyzed indications for prescribing strong opioids by the general practitioner (GP). Results A total of 18,433 analgesic users were identified. Over time, prescriptions for paracetamol, NSAIDs and weak opioids decreased, while the number of strong opioid prescriptions increased. General practitioners prescribed more strong opioids for non-malignant pain, whereas prescriptions for malignant pain remained stable over time. Risk factors for chronic opioid use (≥90 days) included older age, lower educational level, smoking status and having a history of a musculoskeletal or psychological disorder, a malignancy or sexual, physical or psychological abuse. Conclusions Considering the increase in strong opioid prescriptions for benign conditions, GPs need to be vigilant for patients who are at risk for chronic use. Regular monitoring and awareness for psychosocial factors in treatment of chronic pain may be key in preventing harms associated with persistent opioid use.

A Propensity Score-Based Comparison regarding Renal, Functional, and Surgical Outcome of Continent Cutaneous Urinary Diversions in Patients with Benign Chronic Bladder Diseases and Patients with Bladder Cancer.

Continent cutaneous urinary diversion post-cystectomy is an established approach addressing both oncological and functional indications. However, there is a noticeable gap of evidence when it comes to comparing outcomes between these indications, especially concerning the technique of Mainz pouch I (MPI). This study aimed to close the gap by analyzing the long-term functional and renal outcomes of patients with MPI after cystectomy due to both benign and malign bladder pathologies. In this retrospective study, we examined 173 patients, who underwent MPI surgery between 2000 and 2022. Patients were categorized into a study group (benign conditions, n = 26) and a control group (bladder cancer, n = 52) using propensity score matching. Clinical demographics, surgical outcomes, and functional/renal parameters were analyzed using unpaired t tests and χ2 tests. Patients undergoing cystectomy with MPI due to benign bladder pathologies were significantly younger and had a lower comorbidity burden compared to those with bladder cancer. In contrast to a significantly higher incidence of chemotherapy in the oncological cohort, the long-term renal function was comparable between both populations. Surgical outcomes, revisions, and postoperative complications did not differ significantly between both groups. Nearly 90% of patients in both groups showed full continence. This study demonstrates the efficacy and safety of MPI surgery in both benign and malignant conditions, proving favorable long-term renal and functional outcomes.

One-Pot Sequential Synthesis of Alkenylated Dihydroquinolinones and Hexahydroacridinones in Deep Eutectic Solvent Medium.

The sequential synthesis of N-heterocycles from saturated ketones poses significant challenges and has rarely been reported. Herein, an efficient synthesis of alkenylated dihydroquinolinones 7 and hexahydroacridinones 8 is achieved from saturated ketones 1 or 2 via dehydrogenation, cyclization, oxidation, and α-alkenylation in choline chloride-based deep eutectic solvent (DES) medium. This strategy provides alkenylated dihydroquinolinones 7 and hexahydroacridinones 8 in excellent yield from low-cost, readily available starting materials under environmentally benign conditions. Furthermore, the synthesized compounds (4, 5, 7, and 8) were investigated for their photophysical properties through absorption and emission spectral studies.

Wolbachia-infected pharaoh ant colonies have higher egg production, metabolic rate and worker survival.

Wolbachia is a widespread maternally transmitted endosymbiotic bacteria with diverse phenotypic effects on its insect hosts, ranging from parasitic to mutualistic. Wolbachia commonly infects social insects, where it faces unique challenges associated with its host's caste-based reproductive division of labor and colony living. Here, we dissect the benefits and costs of Wolbachia infection on life-history traits of the invasive pharaoh ant, Monomorium pharaonis, which are relatively short lived and show natural variation in Wolbachia infection status between colonies. We quantified the effects of Wolbachia infection on the lifespan of queen and worker castes, the egg-laying rate of queens across queen lifespan, and the metabolic rates of whole colonies and colony members. Infected queens laid more eggs than uninfected queens but had similar metabolic rates and lifespans. Interestingly, infected workers outlived uninfected workers. At the colony level, infected colonies were more productive as a consequence of increased queen egg-laying rates and worker longevity, and infected colonies had higher metabolic rates during peak colony productivity. While some effects of infection, such as elevated colony-level metabolic rates, may be detrimental in more stressful natural conditions, we did not find any costs of infection under relatively benign laboratory conditions. Overall, our study emphasizes that Wolbachia infection can have beneficial effects on ant colony growth and worker survival in at least some environments.

High-Performance Metabolic Profiling of High-Risk Thyroid Nodules by ZrMOF Hybrids.

Thyroid nodules (TNs) have emerged as the most prevalent endocrine disorder in China. Fine-needle aspiration (FNA) remains the standard diagnostic method for assessing TN malignancy, although a majority of FNA results indicate benign conditions. Balancing diagnostic accuracy while mitigating overdiagnosis in patients with benign nodules poses a significant clinical challenge. Precise, noninvasive, and high-throughput screening methods for high-risk TN diagnosis are highly desired but remain less explored. Developing such approaches can improve the accuracy of noninvasive methods like ultrasound imaging and reduce overdiagnosis of benign nodule patients caused by invasive procedures. Herein, we investigate the application of gold-doped zirconium-based metal-organic framework (ZrMOF/Au) nanostructures for metabolic profiling of thyroid diseases. This approach enables the efficient extraction of urine metabolite fingerprints with high throughput, low background noise, and reproducibility. Utilizing partial least-squares discriminant analysis and four machine learning models, including neural network (NN), random forest (RF), logistic regression (LR), and support vector machine (SVM), we achieved an enhanced diagnostic accuracy (98.6%) for discriminating thyroid cancer (TC) from low-risk TNs by using a diagnostic panel. Through the analysis of metabolic differences, potential pathway changes between benign nodule and malignancy are identified. This work explores the potential of rapid thyroid disease screening using the ZrMOF/Au-assisted LDI-MS platform, providing a potential method for noninvasive screening of thyroid malignant tumors. Integrating this approach with imaging technologies such as ultrasound can enhance the reliability of noninvasive diagnostic methods for malignant tumor screening, helping to prevent unnecessary invasive procedures and reducing the risk of overdiagnosis and overtreatment in patients with benign nodules.

Multimodal analysis of methylation and fragmentomic profiles in plasma cell free DNA for differentiation of benign and malignant breast tumors.

7 Background: Breast cancer ranks as the second leading cause of cancer-related mortality among women globally. Early detection of breast cancer is crucial for improving patient outcomes and reducing mortality rates. Liquid biopsy, which relies on circulating tumor DNA (ctDNA) shed by breast tumors into the bloodstream, presents a promising non-invasive approach for early breast cancer detection. However, accurately distinguishing between benign breast abnormalities and malignant tumors remains a significant clinical challenge, as misdiagnosis can lead to unnecessary invasive procedures. Methods: Herein, we employed a multimodal analysis approach, namely SPOT-MAS (Screen for the Presence of Tumor by DNA Methylation and Size), to profile alterations in methylation and fragment length patterns of cell-free DNA (cfDNA) from 169 breast cancer-confirmed patients and 99 patients diagnosed with benign breast lumps including cysts, fibroadenomas, and fibrocystic changes. A robust machine learning model was constructed using these signatures to differentiate between breast cancer patients and individuals with benign lesions. Results: Our genome-wide analyses identified distinct profiles of methylation changes, copy number alterations, and end motifs in cfDNA, enabling discrimination between breast cancer patients and individuals with benign conditions. Notably, we observed a significant enrichment of Thymine and Adenine at cfDNA cleavage sites in breast cancer patients. Moreover, our target sequencing analyses uncovered distinct methylation patterns in the regulatory regions of multiple genes, including hypermethylation in GPR126 or hypomethylation in TOP1 or MAFB in breast cancer cfDNA. Our multi-featured model achieved an AUC of 0.92 (95% CI: 0.88–0.97), a specificity of 97.44% and sensitivities of 57.14% and 61.70% for stage I and stage II–III patients, respectively. Furthermore, our multimodal assay effectively differentiated multiple molecular subtypes of breast tumors from benign lesions, achieving the highest sensitivity of 71.43% with Luminal A, followed by Luminal B, Triple Negative Breast Cancer (TNBC), Luminal B-HER2, and HER2 with sensitivities of 66.67%, 60%, 58.33% and 55.56%, respectively. Conclusions: Our findings demonstrate the potential of cancer-specific methylation and fragmentomic patterns in plasma cfDNA as novel biomarkers for accurately discriminating between breast cancer and benign lesions. This capability reduces the false-positive rate and helps avoid unnecessary biopsies in current clinical practice.

Enhanced Electrohydrogenation of Cis,Cis-Muconic Acid to Trans-3-Hexenedioic Acid Using Hybrid Metal/Carbon Fiber Cathodes

Organic electrosynthesis is a long-known technique for diverse product development and efficient synthesis. With the recent rise of biomass as an alternative carbon and energy source, electrochemistry is further gaining popularity due to its inherently green and environmentally benign operating conditions. Electrochemical hydrogenation (ECH) reactions are particularly attractive for biomass conversion due to their ability to abstract hydrogen from water, tolerate biogenic impurities, and utilize Earth-abundant base metal electrodes. Moreover, the rate and selectivity of the reaction can be tubed by controlling the electrode material, operating potential/current density, and reactor design. However, the implementation of this decarbonized technology for chemical production is still hampered by low productivity and, as a result, unfavorable economics. cis,cis-Muconic acid (ccMA), a bioderived C6 diunsaturated diacid platform molecule, can be converted into commodity chemicals like caprolactam, adipic acid (AA), and terephthalic acid, with AA being of particular interest for the synthesis of nylon 6,6.1 Apart from various drop-in chemicals, ccMA can also be electrochemically upgraded to trans-3-hexenedioic acid (t3HDA), a potential bio-advantaged substitute for AA as the additional C=C bond in t3HDA can be leveraged to synthesize performance-advantaged polyamides.2,3 In this work, we investigated the electrohydrogenation of ccMA to t3HDA over Pb cathodes. We demonstrate that the reaction follows a radical-based pathway involving sequential electron transfer and hydrogen addition in solution to selectively produce t3HDA (100% selectivity). Next, we contacted the cathode with carbon felts (CF) to increase productivity. CF are often used in fuel cells and H2O2 electrolyzers due to their excellent conductivity, porosity for enhanced turbulence, and ability to tune the gas-liquid-solid three-phase interface. Following similar principles, we placed a CF (3mm. thickness) in contact with the Pb cathode to lower the charge transfer resistance (~3Ω) at the interface. The surface functionalities of carbon allowed us to further tune the hydrophobicity/hydrophilicity of our hybrid electrode. Molecular dynamics (MD) calculations provided critical insights into the role of surface functionalities and guided the optimal functionalization of CF’s surface. Combining reactor configuration with fine-tuning of the electrode’s microenvironment, we were able to achieve a 50x increase in t3HDA productivity reaching up to 20 g/cm2/day at a current density of 200 mA/cm2. We further replaced the kinetically sluggish oxygen-evolution reaction with the glucose oxidation reaction at the anode, allowing us to operate the electrolyzer at a lower cell potential.Overall, ECH represents a valuable alternative to thermochemical transformations for biomass upgrading. This work provides critical insights into reactor modifications for the scaled-up synthesis of bio-derived performance monomers via hybrid microbial electrosynthesis (HMES).

An unusual case of HHV-8 negative, idiopathic, multicentric Castleman disease following chronic lymphocytic leukaemia

Background: Castleman disease is a rare condition characterised by polytypic lymphocytes proliferation and lymphadenopathy generally with a benign course. Whereas high grade lymphoma (Richter syndrome) is a classical complication seen in chronic lymphocytic leukaemia with a poor outcome, benign conditions mimicking this entity are infrequent. Case description: We describe the case of an 81-year-old Caucasian male who developed a human herpesvirus-8 (HHV-8)–negative, idiopathic multicentric Castleman disease (iMCD) following a treated Binet C chronic lymphocytic leukaemia (CLL). The clinical and radiological pattern raised initially the suspicion of a classical Richter transformation. Blood analysis showed auto-immune haemolytic anaemia and thrombocytopenia. He had normal immunoglobulin levels. The anatomopathological analysis of a cervical adenomegaly showed hypervascularisation and a polytypic plasmocytic proliferation compatible with a plasmocytic iMCD type. Interestingly, bone marrow examination showed reticuline fibrosis but, in the absence of anasarca or generalised oedema, we were not allowed to conclude to the diagnosis of a TAFRO syndrome. We exclude all other mimicking conditions, comprising haematological malignancies, infections, and auto-immune diseases He was first treated with corticosteroids with poor results but dramatically responded to tocilizumab (anti-Il6). Conclusion: To our knowledge, this the first case described of a Castleman disease following CLL and surprisingly mimicking Richter syndrome. Clinicians should be aware of this rare misleading condition.

Identification of a serum proteomic biomarker panel using diagnosis specific ensemble learning and symptoms for early pancreatic cancer detection.

The grim (<10% 5-year) survival rates for pancreatic ductal adenocarcinoma (PDAC) are attributed to its complex intrinsic biology and most often late-stage detection. The overlap of symptoms with benign gastrointestinal conditions in early stage further complicates timely detection. The suboptimal diagnostic performance of carbohydrate antigen (CA) 19-9 and elevation in benign hyperbilirubinaemia undermine its reliability, leaving a notable absence of accurate diagnostic biomarkers. Using a selected patient cohort with benign pancreatic and biliary tract conditions we aimed to develop a data analysis protocol leading to a biomarker signature capable of distinguishing patients with non-specific yet concerning clinical presentations, from those with PDAC. 539 patient serum samples collected under the Accelerated Diagnosis of neuro Endocrine and Pancreatic TumourS (ADEPTS) study (benign disease controls and PDACs) and the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, healthy controls) were screened using the Olink Oncology II panel, supplemented with five in-house markers. 16 specialized base-learner classifiers were stacked to select and enhance biomarker performances and robustness in blinded samples. Each base-learner was constructed through cross-validation and recursive feature elimination in a discovery set comprising approximately two thirds of the ADEPTS and UKCTOCS samples and contrasted specific diagnosis with PDAC. The signature which was developed using diagnosis-specific ensemble learning demonstrated predictive capabilities outperforming CA19-9, the only biomarker currently accepted by the FDA and the National Comprehensive Cancer Network guidelines for pancreatic cancer, and other individual biomarkers and combinations in both discovery and held-out validation sets. An AUC of 0.98 (95% CI 0.98-0.99) and sensitivity of 0.99 (95% CI 0.98-1) at 90% specificity was achieved with the ensemble method, which was significantly larger than the AUC of 0.79 (95% CI 0.66-0.91) and sensitivity 0.67 (95% CI 0.50-0.83), also at 90% specificity, for CA19-9, in the discovery set (p = 0.0016 and p = 0.00050, respectively). During ensemble signature validation in the held-out set, an AUC of 0.95 (95% CI 0.91-0.99), sensitivity 0.86 (95% CI 0.68-1), was attained compared to an AUC of 0.80 (95% CI 0.66-0.93), sensitivity 0.65 (95% CI 0.48-0.56) at 90% specificity for CA19-9 alone (p = 0.0082 and p = 0.024, respectively). When validated only on the benign disease controls and PDACs collected from ADEPTS, the diagnostic-specific signature achieved an AUC of 0.96 (95% CI 0.92-0.99), sensitivity 0.82 (95% CI 0.64-0.95) at 90% specificity, which was still significantly higher than the performance for CA19-9 taken as a single predictor, AUC of 0.79 (95% CI 0.64-0.93) and sensitivity of 0.18 (95% CI 0.03-0.69) (p = 0.013 and p = 0.0055, respectively). Our ensemble modelling technique outperformed CA19-9, individual biomarkers and indices developed with prevailing algorithms in distinguishing patients with non-specific but concerning symptoms from those with PDAC, with implications for improving its early detection in individuals at risk.

Evaluating no fixation, endoscopic suture fixation, and an over-the-scope clip for anchoring fully covered self-expanding metal stents in benign upper gastrointestinal conditions: a comparative multicenter international study (With Video)

Fully covered self-expandable metal stents (FCSEMSs) are widely used in benign upper gastrointestinal (GI) conditions, but stent migration remains a limitation. An over-the-scope clip (OTSC) device (Stentfix {SF], Ovesco Endoscopy) for stent anchoring has recently been developed. The aim of this study was to evaluate the effect of OTSC fixation on FCSEMS migration rate. In this retrospective review of consecutive patients who underwent FCSEMS placement for benign upper GI conditions from January 2011 to October 2022 at 16 centers, the primary outcome was rate of stent migration. The secondary outcomes were clinical success and adverse events. A total of 311 (no fixation [NF] 122, SF 94, endoscopic suturing [ES] 95) patients underwent 316 stenting procedures. Compared with the NF group (n= 49, 39%), the rates of stent migration were significantly lower in the SF (n= 16, 17%, P= .001) and ES (n= 23, 24%, P= .01) groups. The rates of stent migration were not different between the SF and ES groups (P= .2). On multivariate analysis, SF (odds ratio [OR], 0.34, 95% CI, 0.17-0.70, P< .01) and ES (OR, 0.46, 95% CI, 0.23-0.91; P= .02) were independently associated with decreased risk of stent migration. Compared with the NF group (n= 64; 52%), there were higher rates of clinical success in the SF (n= 64; 68%; P= .03) and ES (n= 66; 69%; P= .02) groups. There was no significant difference in the rates of adverse events among the 3 groups. Stent fixation using OTSCs is safe and effective at preventing stent migration and may also result in improved clinical response.

Ophthalmologic Implications of Connective Tissue Diseases: A Comprehensive Review of Current Knowledge and Innovations.

Connective tissue diseases (CTDs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome, and systemic sclerosis (SSc), represent a diverse group of disorders characterized by abnormalities in the proteins that support tissues and organs. These diseases can affect multiple organ systems and are often associated with significant morbidity and mortality. The eyes are frequently affected among the various organ systems involved, with ocular manifestations ranging from benign conditions such as dry eye syndrome to severe, sight-threatening complications like scleritis, retinal vasculitis, and optic neuritis. Recognizing and managing these ophthalmologic implications is crucial for preventing severe complications, providing diagnostic clues, and improving patients' quality of life. This comprehensive review aims to elucidate the current knowledge and innovations related to the ophthalmologic implications of CTDs. It details the ocular manifestations associated with major CTDs, explores diagnostic approaches to identifying and differentiating these conditions, and discusses management strategies, including pharmacological and surgical interventions. Additionally, the review highlights recent advancements and emerging therapies in diagnosing and treating CTD-related ophthalmologic conditions. The review also addresses this field's challenges and future directions, emphasizing the importance of interdisciplinary collaboration and continuous research. By synthesizing the latest research and clinical insights, this review seeks to enhance the understanding of healthcare professionals regarding the interplay between CTDs and ocular health, ultimately contributing to improved patient care and outcomes.

Comparison of clinical/histological outcomes according to puncture sites in endoscopic ultrasound-guided fine needle biopsy for large pancreatic masses: Multicenter randomized prospective pilot study.

There are no recommendations regarding the optimal puncture site in endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). This multicenter randomized prospective study compared the diagnostic accuracy and histological findings according to the sampling site for pancreatic masses larger than 3 cm. Consecutive patients with pancreatic masses larger than 3 cm indicated for EUS-FNB were included in the study. Patients were randomly assigned to two groups for the initial puncture site (central vs. peripheral sampling of the masses). A minimum of four passes were performed, alternating between the center and the periphery. The primary outcome was diagnostic accuracy. A total of 100 patients were equally divided into the central group and the peripheral group. The final diagnosis revealed malignancy in 95 patients (pancreatic cancer [n = 89], neuroendocrine tumor [n = 4], lymphoma [n = 1], metastatic carcinoma [n = 1]), and benign conditions in five patients (chronic pancreatitis [n = 4], autoimmune pancreatitis [n = 1]). There was no significant difference in diagnostic accuracy between the puncture sites. However, combining samples from both areas resulted in higher diagnostic accuracy (97.0%) compared to either area alone, with corresponding values of 88.0% for the center (P = 0.02) and 85.0% for the periphery (P = 0.006). Both central sampling and peripheral sampling showed equivalent diagnostic accuracy in detecting malignancy. However, combining samples from both areas generated superior diagnostic yield compared to using either sampling site alone. For pancreatic masses larger than 3 cm, it is advisable to consider sampling from various areas of the masses to maximize the diagnostic yield.