Cardiac activity monitoring is important for assessing cardiovascular status and supporting computational analysis of heart-rate pattern variations from wearable PPG signals. The development of wearable devices and public datasets has made continuous and noninvasive monitoring more viable. However, there are still problems that may impair the effectiveness of the technique such as motion artifact, signal noises, changes in the physiological states, and differences in sensor quality. Moreover, it is hard to create algorithms that would be highly accurate in the real-life scenario and would be able to generalize among diverse populations. These problems should be resolved in order to produce reliable, robust, and computationally consistent heart-rate pattern classification frameworks. Hence, this research paper proposes a cardiac activity monitoring-based Heart Rate Classification (CAM-HRC) model with the help of an intelligent deep learning approach. The data was first obtained on the standard benchmark sources referred to as WildPPG: A Real-World photoplethysmography (PPG) Dataset. Preprocessing at the baseline level in the collected data was obtained through data cleaning and normalization techniques. The Temporal Attentive U-Net (TAU) method was used to divide these pre-processed data into segments. These features were then extracted from segmented data with Self-Supervised Multi-Encoder Autoencoder (MEAE) method. The last stage was the classification of these extracted features with CAM-HRC model and the newly added Enhanced Bidirectional Long Short-Term Memory (EBiLSTM). The parameter tweaking of the traditional BiLSTM model was done with the help of a nature-inspired optimization algorithm known as Salamander Optimization Algorithm (SOA). The objective function of the whole process of proposed CAM-HRC model is taken as accuracy maximization. The suggested EBiLSTM-SOA model will divide the final heart rate output into four classes, normal heart rate, Tachycardia, Bradycardia and Rhythm Irregularity. The accuracy and specificity of the proposed EBiLSTM-SOA model of the CAM-HRC are 24.70 per cent and 19.44 per cent higher than the other methods of traditional approaches, respectively.

This study evaluated the efficacy and safety of standard-dose ursodeoxycholic acid (UDCA; fixed daily dose of 300 mg/day) compared with placebo, in patients with chronic liver disease. A multicenter, randomized, double-blind, placebo-controlled phase IV clinical trial was conducted in academic hospitals in South Korea. Patients with chronic liver disease and abnormal serum alanine aminotransferase (ALT) levels in at least two consecutive results prior to screening, persisting for at least 6 months, were randomly assigned to receive 100 mg UDCA or placebo three times daily for 8 weeks. The primary endpoint was the mean relative change in ALT levels from baseline. The secondary endpoints included changes in fibrosis and drug-related adverse events. A total of 262 patients were analyzed (132 in the UDCA group and 130 in the placebo group). By week 8, there was a significantly greater reduction in serum ALT levels from baseline in the UDCA-treated patients than in the placebo group (-14.70 vs. -5.51 U/L; P = 0.010). The ALT normalization rates were higher in the UDCA group (26.52% vs. 13.08%; odds ratio, 2.60; P = 0.005). Fibrosis reduction, as assessed by the FibroTest score, was greater in the UDCA group (-0.03 vs. -0.00; P = 0.016). The frequency of adverse events in the two groups was similar, with no serious adverse events reported in the UDCA group. In patients with chronic liver disease, 100 mg UDCA three times daily for 8 weeks improved ALT levels and fibrosis, and had a favorable safety profile. ClinicalTrials.gov Identifier: NCT06272630.

To evaluate the impact of hepatitis B virus (HBV) carrier status on oocyte quality, embryonic development, and pregnancy outcomes in women with varying ovarian reserve undergoing in vitro fertilization and embryo transfer (IVF-ET). This retrospective study included 112 infertile women with HBV carrier status and 104 HBV-negative controls who underwent IVF-ET between December 2020 and December 2024. Participants were stratified by serum anti-müllerian hormone levels into low (<2 μg/L), normal (2–7 μg/L), and high (>7 μg/L) ovarian reserve groups and further categorized as HBV carriers or noncarriers. Key reproductive outcomes – including cleavage rate, implantation rate, normal fertilization rate, high-quality embryo rate, clinical pregnancy rate, and miscarriage rate – were compared between groups. Across all ovarian reserve strata, HBV carriers exhibited significantly higher rates of unavailable embryos (P <.05). Within the normal ovarian reserve group, HBV carriers had significantly lower cleavage rate, implantation rate, normal fertilization rate, high-quality embryo rate, and clinical pregnancy rate compared to noncarriers (P <.05). No significant differences were observed in the low or high ovarian reserve groups. Miscarriage rates were elevated among HBV carriers across all ovarian reserve categories (P <.05). HBV infection may adversely affect oocyte quality and embryonic development, particularly in women with normal ovarian reserve, resulting in compromised IVF-ET outcomes. These findings highlight the potential need for early reproductive intervention in this population.

Impact of the antimicrobial stewardship incentive program on antimicrobial supply instability: An interrupted time-series analysis using national drug supply data.

Tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) are considered efficacious and safe nucleoside/nucleotide analogs (NAs) for patients with chronic hepatitis B (CHB). However, real-world data on TMF for CHB patients with low-level viremia (LLV) remain scarce. This study investigated the real-world effectiveness and safety of TMF combined with entecavir (ETV) in the treatment of CHB patients with LLV, and compared the efficacy and safety of TMF combined with ETV and tenofovir alafenamide (TAF) combined with ETV in the treatment of CHB patients with LLV. This retrospective real-world study included CHB patients with LLV who received treatment with either TMF combined with ETV or TAF combined with ETV. After the 48-week follow-up, this study evaluated the differences between the two groups in terms of virological response rate (VR rate), ALT normalization rate, HBsAg and HBeAg seroclearance rate, liver fibrosis assessment, and safety endpoints (renal function and blood lipids). A total of 258 patients were enrolled: 123 in the experimental group (TMF combined with ETV) and 135 in the control group (TAF combined with ETV). The levels of HBV DNA and AST in both groups were significantly lower than the baseline levels after 48-week treatment period (P < 0.05). The VR rate at week 48 was 79.67% in the experimental group, while that in the control group was 72.59%, and there was no statistically significant difference between the two groups (P = 0.184). With respect to the ALT normalization rate, HBsAg seroclearance rate, HBeAg seroclearance rate and liver transient elastography (TE) results, no statistically significant differences were detected between the two groups (P > 0.05). Similarly, for the safety endpoints, including serum creatinine (Cr), glomerular filtration rate (eGFR), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels, none of these indicators significantly differed between the two groups. TMF combined with ETV was found to be effective in CHB patients with LLV and appeared to have a favorable safety profile within the limitations of the available data. It exhibits robust antiviral activity and can improve the liver function of patients.

Hypertensive disorders of pregnancy (HDP) contribute significantly to maternal and neonatal morbidity. Precision medicine emphasizes individualized risk prediction, while nursing interventions (NIs) address behavioral and psychosocial care. This study evaluated the clinical benefit of a structured NI compared to routine prenatal care in reducing complications among women diagnosed with HDP. This retrospective quasi-experimental study was conducted at Peking University Shenzhen Hospital. Participants were primigravida Chinese women (median age 25 years) with a confirmed diagnosis of HDP. Of 3260 screened women, 265 met the inclusion criteria: gestational hypertension (48%), preeclampsia (31%), or superimposed preeclampsia (21%). Risk was initially assessed via self-reported questionnaires starting at 15 gestational weeks until 7 days postpartum. Participants were allocated to either an NI (Women with hypertensive disorders of pregnancy received prenatal care and NIs sessions until 7 days postpartum [NI cohort], n = 122), receiving structured education and behavioral sessions, or a routine prenatal care (PR cohort, n = 143). This investigation identifies a significant association between a protocolized NI and improved obstetric trajectories, particularly in younger women and those with a higher body mass index (BMI). While these associative findings are encouraging, the non-randomized, retrospective nature of the study necessitates caution, and the results should be viewed as hypothesis-generating rather than evidence of a definitive causal effect. The study population consisted of primigravida women with a median prepregnancy BMI of 23.8 kg/m2. The NI was independently associated with significantly higher odds of spontaneous vaginal delivery (adjusted odds ratios: 2.15; 95% confidence interval: 1.84-2.51; P < .001). The intervention was independently associated with a significant reduction in the risk of neonatal intensive care unit (NICU) admissions (adjusted odds ratios: 0.28; 95% confidence interval: 0.11-0.72; P = .008). Raw delivery outcomes also favored the NI cohort regarding normal delivery rates (45% vs 17%, P < .0001) and labor duration (82% vs 49%, P < .0001). Maternal complications were comparable, and nausea was significantly lower in the NI group (18% vs 29%, P = .032). Secondary neonatal outcomes demonstrated significant reductions in low birth weight (9% vs 15%, P = .048) and respiratory distress syndrome (3% vs 9%, P = .021). A NI was most effective for women aged ≤25 years and those with a BMI>24 kg/m2.

Coated granular materials are involved in numerous industrial processes, including powder handling in pharmaceuticals, additive manufacturing, cement production, and food processing, where surface treatments control flowability, prevent agglomeration, and improve product consistency. Despite their widespread use, the influence of coatings on the collective behavior of granular materials remains poorly understood. While dry granular flows are well described by the μ(I) rheology for frictional, noncohesive particles, many real-world systems involve additional interparticle interactions that fall outside this framework. Here, we investigate how polymer coatings on silica grains modify dry granular rheology by introducing non-Coulombic frictional behavior at the particle scale. Pressure-imposed rheological experiments reveal that coatings activate a low-friction regime in which the bulk friction coefficient and packing fraction approach values typical of frictionless grains. The transition from this lubricated state to a conventional frictional regime depends on both normal stress and shear rate, indicating stress- and velocity-dependent contact mechanics. Tribological measurements show that interparticle friction decreases with coating thickness and sliding velocity, but increases with normal load. Building on these findings, we develop a mean-field rheological model that extends the classical μ(I) framework to include coating-dependent, non-Coulombic friction. Discrete Element Method simulations incorporating the measured friction law capture the key qualitative features observed experimentally. These results demonstrate that controlled surface coatings provide a powerful route to engineer granular rheology and enhance flowability across various industrial applications.

Muscle atrophy, which is characterized by the loss and dysfunction of skeletal muscle proteins, is a major degenerative condition that is associated with aging and glucocorticoid therapy. Marine-derived compounds, particularly polyphenols, have recently potential in modulating muscle metabolism and regeneration. This study aimed to investigate the effects of the ethanolic extract from Padina arborescens (PAE) on myogenic differentiation and dexamethasone (DEXA)-induced muscle atrophy using C2C12 myotubes and a zebrafish model. PAE treatment significantly promoted myotube differentiation by modulating the Akt/mTOR signaling pathway and enhancing the expression level of myogenic regulatory factors (MyoD and myogenin). In DEXA-treated myotubes, PAE effectively suppressed the ubiquitin proteasome system, restored myosin heavy chain protein synthesis, and recovered myotube morphology. In vivo, PAE supplementation ameliorated the DEXA-induced locomotor dysfunction in zebrafish without causing developmental or neurotoxic abnormalities, as confirmed by the normal survival rate, body length, and heart rate. Collectively, these findings indicated that polyphenol-rich PAE exerts protective and anabolic effects by promoting myogenesis and preventing glucocorticoid-induced muscle degradation. Therefore, PAE may be used as a promising marine-derived therapeutic agent for maintaining skeletal muscle health and preventing muscle atrophy.

Multi-level surgery for obstructive sleep apnoea in syndromic and non-syndromic paediatric patients - A systematic review and meta-analysis.

Myocardial perfusion imaging (MPI) is widely used to assess coronary artery disease (CAD). U.S. studies have reported increasing normal MPI findings over time. However, European data are limited. This study examined temporal trends in pre-test probability (PTP) and MPI findings at a large Swiss centre. In this retrospective study, 45 686 MPI scans were analysed. Clinical data included demographics, symptoms, risk factors, MPI results, and coronary artery calcium score (CACS). Endpoints were defined as abnormal MPI (Summed Stress Score ≥4), small ischaemia (Summed Difference Score ≥2), and relevant ischaemia (≥10% ischaemia). PTP was calculated using the 2013/2019 ESC chronic coronary syndrome (CCS) guidelines, and risk factor-weighted clinical likelihood (RF-CL) from the 2024 guidelines. Normal MPI results increased significantly over time (53% (2000) → 66% (2024), P < 0.001), irrespective of unchanged PTP/RF-CL, modality, type of stress, symptoms and risk factors. Small ischaemia decreased (37.6% → 34.2%), while relevant ischaemia increased (11.0% → 13.2%, P < 0.001 each) slightly. SSS and SRS decreased significantly, whereas SDS remained unchanged. CACS and the prevalence of zero CACS remained unchanged over time. ESC PTP models overestimated the prevalence of abnormal MPI and small ischaemia. Only RF-CL predicted relevant ischaemia correctly in very low-risk patients. The rate of normal MPI results increased over time, but the trend was less pronounced than previously published. Possible explanations include referral of healthier patients (unchanged CACS despite increasing age), less typical angina, a lower prevalence of established CAD, and more female patients.

Vancomycin is a widely prescribed antibiotic used in the treatment of gram-positive bacterial infections. We previously showed that this antibiotic disrupted protective antifungal immune responses via microbiome dysbiosis, enhancing susceptibility to invasive candidiasis. Antibiotics are an independent risk factor for developing this life-threatening fungal infection, but whether microbiota-independent mechanisms also drive this association is not clear. Here, we show that vancomycin directly impairs macrophage responses to Candida albicans, the main causative agent of invasive candidiasis. Vancomycin-treated macrophages were less able to kill C. albicans despite normal phagocytosis rates and were hyper-inflammatory and more likely to die during infection. Using a fluorescently labeled vancomycin, we observed vancomycin uptake by macrophages in vivo and within close proximity to the mitochondrial outer membrane. Vancomycin treatment led to a significant depolarization, reduced respiratory capacity, and a hyper-fragmented morphology of mitochondria, as well as increased cellular ROS production. Taken together, this work demonstrates direct effects of vancomycin on mammalian immune cells, helping us to understand the pro-inflammatory effects of this drug and how it promotes susceptibility to life-threatening fungal infection.IMPORTANCEAntibiotics are widely prescribed drugs used to treat bacterial infections; however, their use may increase the likelihood of developing life-threatening fungal infections in vulnerable patients. Candida albicans is a commensal fungus in humans but may cause serious disease in patients with defined risk factors, including antibiotic exposure. We find that the antibiotic vancomycin significantly impairs the ability of macrophages to kill C. albicans yeast. Vancomycin-induced defects in fungal killing were associated with changes to mitochondria in antibiotic-exposed macrophages, which also exhibited enhanced oxidative stress and reduced survival during fungal infection. This work identifies a direct mechanism by which antibiotics may impair antifungal immunity.

Background/Objectives: Chronic otitis media with effusion (OME) is the primary cause of conductive hearing loss in children. High recurrence rates following conventional surgery are often linked to incomplete nasopharyngeal clearance or persistent adenotonsillar biofilms. This study evaluates the long-term impact of endoscopic coblation adenotonsillotomy on middle ear clearance and disease recurrence compared to conventional curettage adenoidectomy. Methods: We conducted a prospective comparative study on 142 pediatric patients with persistent OME. Participants were allocated into Group A (Endoscopic Coblation Adenotonsillotomy, n = 72) and Group B (Conventional Curettage Adenoidectomy, n = 70). Groups were homogeneous regarding age, gender, and baseline audiological parameters (p &gt; 0.05), all presenting with moderate conductive hearing loss and Type B/C tympanograms. Primary outcomes included tympanometric normalization (Type A conversion), auditory gain (Air–Bone Gap closure), and the rate of secondary ventilation tube (VT) insertion, monitored at 1, 3, 6, and 12 months. Results: At the 1-month follow-up, Group A showed a higher normalization rate than Group B (75.0% vs. 60.0%), though this was near the threshold of statistical significance (p = 0.058). However, at 3, 6, and 12 months, the coblation group demonstrated significantly higher recovery rates (p &lt; 0.05). By 12 months, 94.4% of Group A maintained a Type A tympanogram compared to 78.5% in Group B. Group A achieved a significantly lower mean ABG at 12 months (8.2 ± 3.1 dB vs. 12.6 ± 5.4 dB, p &lt; 0.001), reflecting a superior auditory gain (20.2 dB vs. 15.3 dB). Furthermore, the recurrence rate was significantly lower in Group A (4.1% vs. 15.7%, p = 0.021), resulting in a substantially lower requirement for secondary VT insertion compared to the conventional group (2.7% vs. 12.8%, p = 0.018). Conclusions: Endoscopic coblation adenotonsillotomy provides significant long-term clinical advantages over conventional curettage. By ensuring precise, atraumatic clearance of the Fossa of Rosenmüller and addressing the tonsillar biofilm reservoir, this technique achieves more stable middle ear aeration and superior auditory recovery, significantly reducing the necessity for secondary surgical interventions at one year.

Tenofovir alafenamide (TAF) has emerged as a safe and effective alternative to entecavir (ETV) in the management of chronic hepatitis B (CHB). We aimed to evaluate the efficacy and safety of switching to TAF compared with maintaining ETV in patients with CHB who had achieved virologic suppression on ETV. In this multicenter, randomized, open-label, active-controlled, noninferiority clinical trial conducted at 13 Korean centers, 196 CHB patients who had experienced virologic suppression after ≥24 weeks of ETV therapy were randomized 1:1 to switch to TAF (n=95) or continue on ETV (n=101). The primary endpoint was the proportion of patients with hepatitis B virus (HBV) DNA <29 IU/mL at week 48 (per-protocol set). Secondary endpoints included alanine aminotransferase (ALT) normalization, hepatitis B surface antigen and hepatitis B e antigen serologic responses, and safety outcomes. Among 188 patients in the per-protocol set (89 TAF, 99 ETV), the HBV suppression rate at week 48 was 100.0% in the TAF group and 99.0% in the ETV group (difference, 1.03%; one-sided 97.5% confidence interval, -0.96 to infinity). ALT normalization rates at week 48 were comparable between groups (55.0% in TAF vs 38.7% in ETV; p=0.26; American Association for the Study of Liver Diseases criteria). Hepatitis B e antigen seroconversion rates were also similar at week 48 (0.0% vs 12.5%; p=0.21). Safety profiles, including renal function, did not significantly differ between the two groups. Switching from ETV to TAF was noninferior to continuing ETV in maintaining virologic suppression, with comparable biochemical, serologic, and safety outcomes. (ClinicalTrials. gov identifier NCT06000657).

Saltbush (Atriplex hortensis L.) and birch leaves (Betulae folia) are ubiquitous raw materials with a wide range of useful properties. This research focused on the actoprotective effect that a mixed aqueous extract of these two plants had on laboratoryrats subjected to forced swim test. The experiment included an intact group (control), rats that received treatment but underwent a forced swim test, and rats that were administered with the experimental aqueous extract of A. hortensis and Betulae folia followed by the forced swim test. The mixed extract of A. hortensis and Betulae folia (Kemerovo Region, Russia) was administered intragastrically to threemonth-old male Wistar rats (4 mL/100 g body weight) who performed daily 2-h swimming sessions for two weeks. The chemical analysis of the extract revealed the presence of flavonoids (quercetin, luteolin, kaempferol), 8 essential amino acids, and 17 amino acids, including amino acids with a branched side chain (valine, isoleucine, leucine). The forced swim test made it possible to study the effect of the extract on the hematological parameters of peripheral blood. The hematological analysis showed that the administration of the extract restored leukocytes, lymphocytes, and hemoglobin to the levels demonstrated by the animals in the intact group. As for the electrocardiographic parameters, the swimmers demonstrated a faster depolarization of the heart chambers while maintaining normal heart rate, which denoted an efficient compensation for the hypertrophic changes in the myocardium caused by the physical exertion. In this in-vivo research, the extract of Betulae folia and aerial parts of A. hortensis had no cardiotoxic effect and helped restore the level of blood oxygenation after physical exertion. In the future, the synergetic actoprotective effect of these two widespread plants can be used in dietary supplements and functional foods.

Energy homeostasis at the organismal level requires balancing energy storage and mobilization to provide sufficient fuel for energy-intensive processes like development without depleting or accumulating excess stores. Fluctuations in the nutritional content of the diet present a challenge to the pathways that maintain energy balance. We previously identified the Drosophila melanogaster counterpart of human ARC (activity-regulated cytoskeleton-associated protein) as a brain-expressed protein that regulates energy storage in the major fat storage tissue of the fly, the fat body. Here we show that Arc1 expression in the brain responds to changes in diet and insulin-like peptide levels. Mutating Arc1 perturbs the ability of larvae to maintain normal body fat and rates of development upon dietary changes: mutants develop slower or faster than wild-type on nutrient-poor or nutrient-rich diets, respectively. Excess fat storage in Arc1 mutants becomes an advantage upon starvation, prolonging survival relative to the wild type. In addition to metabolic and neuronal genes, transcriptomic analysis revealed changes in key developmental drivers of development, in both diet-dependent and - independent manners. This study supports a model in which nutrient regulation of Arc1 via insulin-like peptide signaling couples dietary changes to changes in metabolism -- to maintain energy homeostasis -- and production of hormone signals, to support timely development. In this role, Arc1 is a central player in a buffering mechanism that coordinates nutrient availability, organismal metabolism, and developmental rate.

Survival after trans-oral laser microsurgery (TLM) for glottic carcinoma is excellent. However, the voice quality after TLM remains unclear. This study examines voice outcomes following different surgical procedures. A retrospective study of voice outcomes (GRBAS, VHI-10, CSID scores) after TLM. Patients undergoing TLM were studied. We collected the Voice Handicap Index (VHI-10), acoustic analysis (Cepstral Spectral Peak Prominence, CSPP score), and GRBAS rating score. These data were correlated with cancer stage and ELS (surgery type). We studied 102 patients (86 males, 16 females; median age 74). There were 51 type I and 27 type Va resections. The rest underwent types II, III, IV, Vb, VI, and open vertical hemilaryngectomy surgery. The median follow-up time was 5.2 years. The median VHI-10 score was 7.5 (normal < 10). The median CSID score was 27.5 (mild = 20-40). The Average GRBAS score was G1.5, R1, B1, A0, S1.5 (mild = 1, moderate = 2). There was a correlation between the CSID score and the type of cordectomy and surgical stage. There was a statistical difference in Type I ELR resection outcomes compared with all other types in voice outcome (Cohen's d-value > 0.5). Patients often rate their VHI as normal, while objective and perceptual raters rate voices after TLM as showing mild to moderate dysphonia. This low VHI score may be due to cancer survivorship. Understanding the patient experience after TLM surgery and knowing the extent of surgery on voice outcomes can help better counsel patients undergoing TLM.

Mobile data collectors (MDCs) play a very important role in Internet of Things (IoT) sensing networks. However, ensuring their trustworthiness against insider threats, such as on-off attacks and spatiotemporal fabrication, remains a critical challenge. Existing trust evaluation methods frequently struggle with these threats due to insufficient evidence dimensions and the inability to quantify behavioral stability. To address these limitations, this paper proposes an enhanced proactive trust evaluation system based on stability sequence extraction (E-PTES-S). E-PTES-S improves the evaluation accuracy by integrating five factors of evidence, stability-computation mechanisms, and an adaptive weight allocation scheme to maintain robustness even when proactive verification data is scarce. In addition to the usual interaction and proactive verification indicators, regional consistency (TRC) and task timeliness (TTT) are introduced to mitigate location falsification and transmit-time deviations more rigorously. Then, a sliding window technique is used to obtain an integrated evidence sequence, which includes a new continuous stability sequence (FCSS) and traditional credible, untrustworthy, and uncertain sequences. This continuous stability sequence adds a variance-based incentive scheme to measure behavioral stability. Finally, the normalized trust value is derived from multiple indicators including multidimensional spatiotemporal evidence and stability metrics. Experimental results show that the proposed E-PTES-S achieves a normal node detection rate of 98.7% under complex dynamic conditions, outperforming the baseline PTES and Trust-SIoT algorithms by approximately 9% and 1%, respectively, while also improving the cumulative data collection profit by 4.8%. Furthermore, robustness analysis demonstrates that E-PTES-S exhibits excellent robustness against physical-layer uncertainties, successfully sustaining an 84.4% detection rate even under severe environmental shadowing.

Objective: To investigate the influencing factors of fertilization failure in in vitro fertilization-embryo transfer (IVF-ET), so as to conduct clinical predictions and reduce the fertilization failure rate. Methodology: A retrospective study was conducted on 1,818 IVF-ET cycles with natural sperm-egg fusion performed in the Department of Reproductive Medicine at the Maternity &amp; Child Care Center of Qinhuangdao from January 2022 to December 2024. These cycles were divided into two groups: the experimental group (218 cycles) with fertilization failure-related adverse outcomes and the control group (1,600 cycles) with normal fertilization. Univariate analysis was first applied to compare general characteristics, endocrine parameters, gonadotropin-related indices, oocyte and sperm parameters, and infertility causes between the two groups. Subsequently, factors with a statistical difference (P &lt; 0.05) in the univariate analysis were enrolled in a multivariate logistic regression model to identify independent influencing factors of fertilization failure. Results: Univariate analysis showed that infertility duration, primary infertility, non-tubal infertility factors, serum estradiol (E2) and luteinizing hormone (LH) levels on the day of human chorionic gonadotropin (HCG) administration, total oocyte yield, sperm motility, normal sperm morphology rate, and post-processing sperm concentration were all associated with IVF fertilization failure. Multivariate logistic regression analysis further identified primary infertility, non-tubal infertility factors, and elevated LH levels on the day of HCG administration as independent risk factors for fertilization failure. Conclusion: Clinical attention should be prioritized for female patients with primary infertility caused by non-tubal factors and elevated LH levels on the day of HCG administration, as these factors independently increase the risk of fertilization failure; targeted clinical interventions for such cases may help reduce the incidence of fertilization failure in IVF-ET cycles.

Coexisting pituitary lesions may range from clinically non-functioning adenomas to hormonally active tumors such as prolactinomas and growth hormone (GH) or thyrotropin (TSH)-secreting adenomas. A 22-year-old male presented with a two-month history of generalized tonic-clonic seizures, accompanied by signs of intracranial hypertension, including intermittent frontal headaches resistant to analgesics and a sudden decrease in visual acuity. He also reported a 20 kg weight gain and an increase in shoe size from 40 to 44 over a seven-month period, without any decline in libido. Clinical examination revealed normal blood pressure and heart rate, and no dysmorphic features, particularly no acromegaloid characteristics. The patient had moderate obesity (BMI: 34 kg/m²), bilateral gynecomastia, mild violaceous striae, no galactorrhea, and was classified as Tanner stage G5P5. Hormonal evaluation showed hyperprolactinemia at 278 ng/mL, central hypothyroidism (TSH: 0.6 mIU/L; free T4: 8 pmol/L), and central hypogonadism (FSH: 1.37 IU/L; LH: 1.1 IU/L; total testosterone: 1.80 ng/mL). IGF-1 was within the normal range (275.8 ng/mL; reference: 120–338). Morning cortisol was 15 µg/dL, with an appropriate suppression after a 1 mg overnight dexamethasone test (0.7 µg/dL). A 24-hour urinary free cortisol measurement was also normal (75 µg/24h). HbA1c was 5.5%. Ophthalmologic examination revealed a normal fundus, but visual field testing showed nasal isopter narrowing. Pituitary MRI demonstrated a well-defined intra- and suprasellar lesion measuring 19 × 16 × 19 mm, consistent with a pituitary macroadenoma. Additionally, an infiltrative cortical and subcortical lesion in the fronto-cingulate region (36 × 24 × 47 mm) suggested a low-grade glioma. The patient was started on cabergoline 0.5 mg twice weekly and levothyroxine 25 µg daily. Neurosurgical intervention for the glioma was performed with gross total resection. Histopathological analysis confirmed a low-grade glial proliferation. Postoperative clinical and biochemical follow-up showed favorable outcomes. This case highlights the need for comprehensive neuroimaging in patients diagnosed with pituitary adenomas who present with atypical neurological symptoms, such as seizures.

ABSTRACT Background &amp; Aims Baseline alkaline phosphatase (ALP) levels can influence the likelihood of achieving dichotomous biochemical response criteria in primary biliary cholangitis (PBC). This concept was explored using Week 52 data from the phase III ELATIVE trial (NCT04526665), which assessed elafibranor, a peroxisome proliferator‐activated receptor α/δ agonist approved as a second‐line treatment for PBC. Methods Patients were grouped by baseline ALP. Outcomes assessed: biochemical response, ALP normalization, ALP change from baseline (CfB), transplant‐free survival (using GLOBE score). Results At Week 52, biochemical response was achieved across all subgroups receiving elafibranor (≤ 2× upper limit of normal [ULN]: 86.7%, &gt; 2–≤ 2.5× ULN: 80.0%, &gt; 2.5–≤ 3× ULN: 52.0%, &gt; 3–≤ 4× ULN: 22.2%, &gt; 4× ULN: 18.8%), and one subgroup receiving placebo (≤ 2× ULN: 13.3%). ALP normalization occurred only with elafibranor (≤ 2× ULN: 53.3%, &gt; 2–≤ 2.5× ULN: 12.0%, &gt; 2.5–≤ 3× ULN: 12.0%, &gt; 4× ULN: 12.5%). Mean ALP reductions were consistent across subgroups receiving elafibranor (overall CfB: −38.9%). Patients receiving elafibranor, regardless of biochemical response, had similar reductions in risk of liver transplant and/or liver‐related mortality within 15 years (−4.0% to −4.5%); among patients receiving placebo, reduced risk was only predicted in responders (−1.5%). Conclusions In ELATIVE, lower baseline ALP correlated with higher biochemical response and ALP normalization rates with elafibranor. However, among patients receiving elafibranor, relative reductions in risk scores and ALP were consistent regardless of biochemical response and pre‐treatment ALP, indicating treatment benefit. Similar biochemical benefits were not observed among patients receiving placebo. These results support evaluating continuous measures and prognostic scores alongside dichotomous criteria to comprehensively assess efficacy. Trial Registration : NCT04526665