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PubMed2026

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans↗

PubMed2026

Role of External Vibratory Lithoclast (Lithecbole) in Improving Lower Pole Stone Clearance After Extracorporeal Shock Wave Lithotripsy (ESWL).

Background and Objective: Extracorporeal shock wave lithotripsy (ESWL) is a widely used non-invasive treatment for renal stones. However, its effectiveness in clearing stones located in the lower pole of the kidney is often limited due to the anatomical challenges that impede the spontaneous passage of fragmented stones. This study evaluate the efficacy and safety of External Physical Vibration Lithecbole (EPVL) when used as an adjunctive therapy following ESWL in patients with lower pole renal stones, with a focus on improving stone clearance rates. Materials and Methods: This prospective interventional study was conducted at Al Yarmouk Teaching Hospital over two years and included 100 patients with 10-15 mm lower pole renal stones. Patients were randomized into two groups: The ESWL alone and ESWL plus EPVL. All patients received two ESWL sessions (3000 shocks/session). The treatment group additionally received EPVL therapy using a flank-applied vibration device. Follow-up was performed using ultrasound and KUB radiography. Statistical analysis was conducted using appropriate tests with significance set at p<0.05. Results: Baseline characteristics, including age, gender, weight, stone size and location, were statistically comparable between groups. The mean stone size was 12.4±1.7 mm. A significantly higher stone-free rate was observed in the ESWL+EPVL group compared to the ESWL-only group (66% vs. 48%, p = 0.027). Although the residual stone size showed a numerical difference favoring EPVL, it was not statistically significant (p = 0.11). Complication rates were low, mild and similar in both groups (p = 0.3). Logistic regression analysis revealed that smaller stone size (p<0.001) and lower patient weight (p = 0.030) were significantly associated with successful stone clearance. Subgroup analysis further confirmed that patients with stones <11 mm or a weight <70 kg had the highest stone-free rates. Conclusion: In this initial evaluation, EPVL demonstrated a safe and effective adjunct to ESWL in enhancing stone clearance for lower-pole renal stones. Its application was associated with improved treatment outcomes without increasing complication rates. Further studies with extended EPVL sessions and longer follow-up are warranted.

Humans↗

PubMed2026

Workforce Representation in Ophthalmology Oral Board Examiners and Examinees.

PURPOSE: To evaluate the characteristics of the American Board of Ophthalmology (ABO) oral board examiners and examinees as well as trends in examiner and examinee gender over time. DESIGN: Retrospective cohort study. SUBJECTS: ABO oral board examiners and examinees. METHODS: We utilized data from the American Board of Ophthalmology (ABO) and Association of American Medical Colleges (AAMC) to assess board examiner and examinee demographic characteristics from 2011 to 2024. Examiner characteristics included gender, years of experience, initial certification year and average examiner score. Examinee characteristics included gender, years since residency graduation and exam outcome (pass/fail). We utilized logistic regression to examine temporal trends in examiner and examinee gender from 2013 to 2024. MAIN OUTCOME MEASURES: Gender distribution of examiners and examinees. RESULTS: Overall, the proportion of women examiners increased over the study period. Notably, the most pronounced increase occurred following the transition from in-person to virtual oral board exam administration in 2020, rising from 31.3% (95% CI: 24.1%-38.4%) in 2019 to 49.1% (95% CI: 43.8%-54.4%) in 2024 (p < .001). The percentage of women examinees remained stable (41.7% [95% CI: 37.6%-45.8%] in 2019; 37.5% [95% CI: 33.0%-42.0%] in 2024, p-value: .019). CONCLUSIONS: The representation of women among the ABO oral board examiners has increased significantly following the transition to virtual exams while the proportion of examinees remained stable. Strategies to increase flexibility in scheduling exams may be beneficial in continuing to improve examiner representation.

Humans↗

PubMed2026

Vaccine preferences and their role for vaccine confidence and uptake: a meta-ethnography.

Vaccine confidence and uptake are influenced by individuals' preferences regarding vaccine composition, quality, or administration pathways. However, literature synthesizing available qualitative insights into individuals' vaccine preferences remains limited. We therefore conducted a meta-ethnographic systematic review of the qualitative literature on vaccine preferences to identify opportunities for enhancing vaccine confidence and uptake. We implemented a comprehensive search strategy and screened 5,528 studies across seven research databases published between 2001 and 2023. We identified and synthesized 97 qualitative articles to delineate factors influencing consumers' vaccine preferences. Our findings revealed four primary domains shaping individuals' vaccine preferences: Product, Place, Price, and Promotion. First, individuals' preferences for vaccines often hinge on perceived quality and safety of the product itself, which can, for example, be associated with vaccine brand or origin, especially in the case of novel vaccines. Second, people prioritize convenience in terms of vaccination sites and delivery methods (wanting vaccinations offered at their doorstep or in local peripheral clinics); evidence regarding preferred groups to administer the vaccines was mixed. Third, the price of vaccines and the secondary costs associated with vaccination played a role in uptake considerations. Finally, both the sources of information (such as healthcare workers, community volunteers, and religious authorities) and the methods of promoting vaccine information (including face-to-face consultations during clinic visits and the distribution of leaflets or banners), emerged as crucial factors shaping decision-making processes. Overall findings highlight the importance of addressing multifaceted preferences to enhance vaccine confidence and uptake. By understanding individuals' vaccine preferences, strategic recommendations can be developed to optimize vaccination programs and ensure acceptability and utilization.

Humans↗

PubMed2026

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans↗

PubMed2026

Preparation and study of non-thrombotic and biostable sulfobetaine-modified small-diameter polyurethane vascular grafts.

A novel sulfobetaine-modified polysiloxane-polycarbonate polyurethane (ZSiPCU) was synthesized. In vitro characterizations revealed that polysiloxane surface enrichment endowed the material with excellent biostability. Importantly, sulfobetaine zwitterions formed a robust hydration layer, effectively suppressing protein adsorption and platelet adhesion to ensure outstanding hemocompatibility. Furthermore, the material supported the adhesion and proliferation of vascular endothelial cells, confirming its cytocompatibility, while its elastomeric matrix provided rapid mechanical self-sealing capabilities. Electrospun ZSiPCU grafts were evaluated in a 3-month rat abdominal aorta model, maintaining high patency rates and facilitating in situ luminal endothelialization and smooth muscle cell remodeling. Additionally, superior puncture resistance of the grafts was demonstrated by puncture tests, with complete hemostasis achieved within 2 mins through mechanical self-sealing.

Polyurethanes↗

PubMed2026

Migration intentions among nigerian neurosurgeons: a national survey of workforce retention.

Physician emigration from low- and middle-income countries creates critical workforce shortages. This study explored factors influencing migration intentions among Nigerian neurosurgeons and trainees. We conducted an anonymized survey of consultant neurosurgeons, fellows, and residents practicing in Nigeria. Invitations were sent by email and professional messaging platforms, and snowball sampling was used to increase participation. The survey included quantitative and open-ended questions on demographics, income, migration plans, and retention factors. Seventy-nine respondents participated (61.5 % consultants; 93.7 % male; median age: 44 years). Nearly all practiced general neurosurgery (97.3 %), and many also performed trauma (65.3 %) and spine (61.3 %) neurosurgery. Most (85.7 %) reported that their earnings were insufficient to support their families. Nearly 40 % were considering emigration, most often citing financial pressures (88.5 %) and poor working conditions (63.5 %) as push factors. By contrast, personal or family ties (63.0 %) and relocation costs (45.2 %) were cited as reasons to stay. Respondents identified higher salaries (58.1 %) and greater investment in the health sector (51.4 %) as key measures to improve retention. In univariable analyses, younger age, income insufficiency, income dissatisfaction, and feeling undervalued at work were associated with migration intention. Financial insecurity emerged as the dominant driver of migration intentions among Nigerian neurosurgeons. In addition to salary increases, sustained investment in healthcare infrastructure and workforce support is essential to improve retention. International partnerships may complement these efforts by building neurosurgical capacity and mitigating brain drain.

Humans↗

PubMed2026

Superficial Cervical Plexus Block and Quality of Recovery after Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Whether adding a bilateral superficial cervical plexus block to a thyroidectomy enhanced recovery pathway improves postoperative quality of recovery remains uncertain. METHODS: In a single-center prospective, randomized, double-blind, placebo-controlled trial in adults undergoing thyroidectomy with general anesthesia, participants were randomized to bilateral superficial cervical plexus blocks with 0.25% bupivacaine or saline. All participants received multimodal analgesia with dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic. The primary outcome was quality of recovery, measured by the QoR-40 survey, on postoperative day 1. Secondary outcomes included the need for rescue opioid, total opioid consumption, nausea, vomiting, antiemetic administration, length of stay in the postanesthesia care unit (PACU), and opioid use on postoperative day 1. RESULTS: A total of 160 participants were randomized to receive a superficial cervical plexus block with bupivacaine 0.25% (n = 78) or saline (n = 82). On postoperative day 1, mean QoR-40 scores were 174 (95% CI, 170 to 178) for bupivacaine and 173 (95% CI, 169 to 177) for saline. The adjusted mean difference between bupivacaine versus saline was 0.91 (95% CI, -3.57 to 5.40; P = 0.688). There were no significant between-group differences in the need for opioids in the PACU or on postoperative day 1, nausea, vomiting, or PACU length of stay. However, the total amount of opioid administered in the PACU was lower in the bupivacaine group (median [interquartile range], 0 [0 to 8]) compared with the saline group (2 [0 to 20]; Hodges-Lehmann location shift, 0 morphine milligram equivalents; 95% CI, -4 to 0; P = 0.017), and fewer participants in the bupivacaine group received rescue antiemetics (3 [3.8%] vs . 13 [16%]; difference, -12%; 95% CI, -22% to -1.8%; P = 0.011). CONCLUSIONS: Bilateral superficial cervical plexus blocks did not improve quality of recovery after thyroidectomy when added to a multimodal analgesic regimen including dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic but were associated with lower total PACU opioid consumption.

Humans↗

PubMed2026

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8 Da), and herbicolin B (1138 Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5 mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5 mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea↗

PubMed2026

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗

PubMed2026

Do wound protectors reduce contamination in total shoulder arthroplasty? A randomized controlled trial.

HYPOTHESIS: Cutibacterium acnes is the most frequent cause of shoulder prosthetic joint infection with skin edges as a source of wound contamination. The primary purpose of this study was to determine if the use of a wound protector device decreases the deep wound bacterial colonization in primary shoulder arthroplasty. The secondary purpose was to assess the effect of device usage on deltopectoral muscle and cephalic vein injury. METHODS: This was a prospective, randomized controlled trial. A total of 100 patients undergoing primary total shoulder arthroplasty were enrolled and randomized into 2 groups: a wound protector group and a control group. Five patients withdrew from the study, leaving 48 patients in the wound protector group and 47 controls. Three deep wound culture swabs were taken after final arthroplasty implantation. The surgeon also graded deltoid, pectoralis major, and cephalic vein injury on a 0-3 scale based on modification to the Tscherne classification of soft tissue injury. The primary outcome of this study was positive culture results for C acnes. Secondary outcomes included total bacterial culture positivity as well as soft tissue injury grades. A subanalysis removing likely contaminant positive cultures (growth >7 days and 1 colony only) was also performed. Comparisons between groups were made using Fisher exact test for categorical outcomes and t tests and Mann-Whitney U tests for continuous variables. RESULTS: The use of a wound protector did not result in any significant differences compared with controls in the rate of positive cultures for C acnes (15% vs. 21%, P = .593) or all bacteria (15% vs. 26%, P = .304). Removing likely contaminant positive cultures did not demonstrate any significant difference in culture positivity (9% vs. 17%, P = .355, for C acnes; 9% vs. 19%, P = .231, for all bacterial species). The wound protector group had better soft tissue injury scores for the deltoid muscle (P < .001) and pectoralis muscle (P < .001). No difference in cephalic vein injury was noted between the 2 groups (P > .05). No difference in surgical time was noted. CONCLUSION: The use of a surgical wound protector device in total shoulder arthroplasty did not significantly decrease bacterial colonization of the deep wound. However, soft tissue damage to the deltoid and pectoralis muscle was less severe in the wound protector group. These findings suggest that this device reduces iatrogenic soft tissue injury.

Humans↗

PubMed2026

Feasibility of implementation, diagnostic accuracy, and end-user impact of an electronic health record (EHR)-based ureteral stent tracking tool in a pediatric population.

INTRODUCTION & OBJECTIVES: Ureteral stent tracking systems have reduced stent retention in adults, but their accuracy and impact in pediatrics have been minimally explored. With low event rates in children, such tools may yield high false positives, raising questions on balancing event prevention with provider burden. We aimed to evaluate the feasibility, diagnostic accuracy, and end-user impact of an Electronic Surveillance Tool for Evaluating Nephroureteral stent Tracking (eSTENT) at our institution. STUDY DESIGN: eSTENT, implemented in 1/2024, flags ureteral stents at risk for retention based on implant documentation, expected explant date, and explant documentation. Monthly reports are generated for stents missing explant documentation. We retrospectively evaluated the diagnostic performance of eSTENT from 1/2024-8/2025 at our pediatric hospital. A usability survey including a validated 1-7 implementation score (higher = easier implementation) was distributed to pediatric urologists and operating room nurses. RESULTS: Of 172 cases with ureteral stent placement, eSTENT flagged 28 events (16%) in 24 patients. Of these, 26 represented documentation gaps where explant had been appropriate. Two flags had no documentation of explant, representing near miss events that were identified. No retained stents occurred, consistent with high sensitivity and modest specificity. There were no flags in the last 6 months of the study period. Survey response rate was 100% for surgeons and 55% for nurses. Before eSTENT, stents were not routinely tracked. All surgeons and 93% of nurses reported no added burden, despite occasional misidentification of retained stents. Three surgeons found eSTENT beneficial, four were neutral, and free-text responses generally cited eSTENT's "fail safe" nature as positive. Nurses suggested improvements, including user support and integrated documentation reminders. The average implementation score among both groups was 6/7, indicating easy adoption. DISCUSSION: While the impact of stent tracking tools in adult literature has been positive, our study emphasizes the feasibility of broader adoption at a pediatric hospital. Integration of eSTENT may avoid the potentially devastating consequences of a retained stent. Prioritizing sensitivity over specificity appears acceptable for a "never event" in patient safety. Our study is limited by the retrospective nature of data collection and survey bias. CONCLUSIONS: Though no stents were retained in the study period, eSTENT appropriately flagged two cases without added burden to most end-users. Further optimization is warranted, but adoption in pediatric centers may enhance care reliability.

Humans↗

PubMed2026

Development and validation of a novel LC-MS/MS method for simultaneous quantification of fidaxomicin and metabolite (OP-1118) from feces for gut pharmacobiome studies.

Fidaxomicin is a first-line antibiotic for treating Clostridioides difficile infection. While it has low systemic absorption and reaches high colonic concentrations, it is hydrolyzed to a less active metabolite, OP-1118. Few studies have completely described critical experimental details of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantifying fecal fidaxomicin and OP-1118. This study developed and validated a simple, fast, and sensitive LC-MS/MS method to quantify fidaxomicin and OP-1118 in human and mouse feces. This method simplified fecal sample preparation without the use of solid phase extraction and optimized LC-MS/MS parameters. A broad working range (0.3-1000 ng/ml) in both diluted human and murine fecal matrices was achieved with good intra- and inter-day accuracy (93-107%), precision (1-7%), and recovery (70-105%) as well as little IS-normalized matrix effects. This method was utilized to quantify fidaxomicin and OP-1118 in human and murine fecal samples. This novel method was simple, fast, sensitive, and accurate in analyzing fecal fidaxomicin and OP-1118 and could be deployed to facilitate gut pharmacobiome research.

Feces↗

PubMed2026

Vortex-assisted liquid-liquid microextraction based on natural deep eutectic solvents for the determination of pyrethroid pesticides in urine.

A novel, facile, and environmentally friendly analytical method was developed based on vortex-assisted liquid-liquid microextraction and high-performance liquid chromatography with diode-array detection for detecting pyrethroid pesticides (PPs) in urine. Natural deep eutectic solvents (NADESs) were prepared using plant essential oil-derived monoterpenoids (thymol, carvacrol, and menthol) combined with aromatic primary alcohols (benzyl alcohol, phenethyl alcohol, and phenylpropyl alcohol) as hydrogen bond donors and acceptors. These solvents served as environmentally benign extraction media, thereby avoiding the use of conventional volatile, toxic organic solvents. NADESs are naturally derived, easy to prepare, biodegradable, and environmentally friendly solvents. Hydrophobic and π-π interactions between the NADESs and PPs may contribute to enhancing the affinity of PPs toward the NADESs phase. Vortex technology, accelerating mass transfer between the sample and extractant phases, enables fast extraction of PPs. Under optimized conditions, the method achieved a low detection limit (0.002 mg L-1), satisfactory precision with relative standard deviations (0.3%-2.4%), and acceptable recovery (80.7%-86.2%). The method demonstrated excellent performance in urine analysis and was feasible as a facile and green strategy for monitoring the content of PPs in biological matrices and assessing exposure risk.

Liquid Phase Microextraction↗

PubMed2026

Sleep stage-dependent distribution of interictal epileptiform discharges in epilepsy: A systematic review.

BACKGROUND: Sleep and epilepsy interact through complex bidirectional mechanisms. Although NREM sleep facilitates interictal epileptiform discharges (IED), the diagnostic contribution of individual sleep stages remains uncertain. In particular, it is unclear whether deeper sleep stages such as N3 provide an advantage over N2 for spike detection or localization in clinical (electroencephalography) EEG practice. METHODS: This systematic review followed PRISMA 2020 guidelines. PubMed and Web of Science were searched for studies reporting quantitative IED measures across sleep stages in patients with epilepsy. Eligible studies included scalp EEG, video-EEG, polysomnography, or intracranial recordings. Mean IED rates per minute were derived when possible. Comparisons between NREM and REM sleep and between N2 and N3 stages were performed using study level non-parametric tests. Risk of bias was assessed with the ROBINS-I tool. RESULTS: Ten observational studies including 266 patients (mean age 30.1 years) were analyzed. IED rates were significantly higher during NREM than REM sleep (Wilcoxon signed-rank test, W = 0, p = 0.0019, r = 0.87). No significant difference was observed between N2 and N3 sleep, although median spike rates were slightly higher during N3 than N2 (0.99 vs 0.86 IED/min). REM showed the lowest activity. CONCLUSIONS: NREM sleep consistently exhibited higher IED rates than REM sleep, reinforcing the neurophysiological association between sleep stage and epileptiform activity without establishing diagnostic superiority.

Humans↗

PubMed2026

Direct background subtraction LC-MS/MS assay for human plasma progesterone: Full validation and comparative application.

OBJECTIVE: To develop and validate a liquid chromatography-tandem mass spectrometry method based on direct background subtraction for the quantification of endogenous progesterone in human plasma. METHODS: Protein precipitation was used for sample preparation with deuterated progesterone as the internal standard. Chromatographic separation was performed on an ACQUITY C18 column using gradient elution with 0.1% formic acid in water and acetonitrile at a flow rate of 0.3 mL/min. Mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Instead of using analyte-stripped matrix or surrogate matrix, authentic plasma was directly used for all validation experiments. Quantitation was achieved by subtracting the background signal, and results were compared with those from the classical method using stripped matrix. RESULTS: Excellent linearity was achieved over 0.1-100 ng/mL (R2 ≥ 0.99). Precision, accuracy, recovery, matrix effect, and stability all met FDA and ICH M10 acceptance criteria. Compared with the classical method, the bias in Cmax and AUC0-t was within ±15%, indicating no significant difference between the two methods. CONCLUSION: The direct background subtraction method avoids laborious preparation of blank matrix, eliminates matrix effect discrepancies, and is simple, efficient, and low-cost. It can serve as a general strategy for endogenous substance determination.

Humans↗

PubMed2026

The effect of monetary versus point-based rewards on effort-cost decision making in individuals at clinical high risk for psychosis.

OBJECTIVE: The dissemination of inexpensive computerized behavioral tasks indexing amotivation may enhance the assessment of clinical high risk (CHR) across settings. However, the impact of varying reward value in such tasks is unclear. If point-based rewards engage participants, this could improve the scalability of computerized assessments. We tested how point-based rewards versus money impacted effort-cost decision-making in CHR individuals. We further assessed how negative symptom severity and household income interacted with reward-type to impact behavior. METHODS: Participants completed the Effort Expenditure for Reward Task (EEfRT). Participants were randomly assigned to receive either money or points for their performance during the EEfRT. Data from a large sample of CHR (N = 233) individuals and healthy controls (HC; N = 157) were collected. RESULTS: Across diagnostic groups, we observed heightened effort expenditure when money was used as a reward (b = 0.13, p = 0.018). We did not find an interaction of CHR status (b = 0.07, p = 0.845) or negative symptoms (b = 0.01, p = 0.429) with reward-type. Within CHR individuals, heightened negative symptom severity was associated with reduced expended effort (b = -0.03, p = 0.016), regardless of reward type. In an exploratory analysis, we found that individuals in the money condition with relatively high household income expended less effort during high reward, high probability trials (b = -0.24, p = 0.046). CONCLUSIONS: Across CHR and HC individuals, individuals pursuing money expended greater effort. While we did not find a group by reward type interaction, CHR individuals with heightened negative symptom severity expended less effort across trials, replicating prior work. Present findings support further study of point-based rewards in tasks indexing amotivation.

Humans↗

PubMed2026

Mitigating pH-induced instability in deruxtecan-based ADCs: an onboard-mixing icIEF approach for robust charge heterogeneity characterization.

Accurate charge variant analysis of antibody-drug conjugates (ADCs) is essential for understanding product heterogeneity and ensuring quality control. However, Deruxtecan (DXd)-based ADCs present a unique analytical challenge due to the intrinsic instability of the payload, where the lactone ring readily undergoes hydrolysis under alkaline conditions, resulting in time-dependent shifts in charge distribution during imaged capillary isoelectric focusing (icIEF). In this study, we describe the development of an onboard-mixing icIEF method designed to minimize pH-induced degradation during sample preparation. By separating ADC samples from carrier ampholytes (CAs) prior to injection and enabling real-time mixing within the instrument, this approach effectively suppresses premature lactone ring opening and stabilizes charge variant profiles. Comparative studies between conventional premixing and onboard-mixing approach demonstrated that the latter significantly enhances reproducibility, particularly for acidic variants that are highly sensitive to structural conversion. Comprehensive method validation confirmed excellent precision, linearity, and sensitivity, with consistent performance across run-to-run and intra-day analyses. The results underscore the importance of controlling microenvironmental pH exposure in the analysis of chemically instable ADCs. The proposed onboard-mixing strategy provides a robust and efficient solution for icIEF-based characterization, reducing analytical artifacts while simplifying method development. This approach is broadly applicable to ADCs and other biotherapeutics containing pH-sensitive functional groups.

Hydrogen-Ion Concentration↗