Browse Articles

A practical approach to replenishment optimization with extended (R, s, Q) policy and probabilistic models

Abstract Effective inventory management is crucial for businesses operating across diverse sales channels, particularly in the dynamic e-commerce landscape. Balancing the need to minimize inventory costs while ensuring sufficient stock availability to meet fluctuating demand presents a significant challenge, further compounded by the complexities of external partnerships and distributed fulfillment networks. These factors introduce uncertainties in demand, returns, and lead times, impacting overall profitability. Recent literature has advanced optimization techniques for production and supply chain systems, often focusing on complex analytical objectives related to imperfect quality, typically solved using meta-heuristics. However, these sophisticated optimization models often rely on deterministic or simplified demand assumptions. This study presents a novel approach to replenishment optimization with a two-fold contribution. First, we aim to bridge the gap through the systematic integration of probabilistic demand forecasting with advanced inventory policy optimization techniques, bridging a critical gap between predictive modeling and practical replenishment decisions. Second, we introduce a significant extension to the classical $$\left( R, s, Q\right)$$ policy framework by Jansen (1996), adapting it to the specific demands of a distributed fulfillment network and highly seasonal assortments. Our Zalando E-commerce Operating System (ZEOS) Inventory Optimization Tool unifies one-shot inventory policy optimization with the predictive power of probabilistic gradient-boosting models (LightGBM). In a backtest covering the full one-year period, the system achieved an aggregate in both Gross Merchandise Value (GMV) and GMV after fulfilment costs uplift compared to the human baseline of $${\sim 22\%}$$ and outperformed all classical inventory-theory baselines (Tuned $$\left( s, S\right)$$ , periodic base-stock, and Myopic newsvendor), with average operational availability and demand fill rate maintained at $${\sim 86\%}$$ and $${\sim 91\%}$$ , respectively. Ablation analyses show that probabilistic forecasts with a percentile-based objective yield the most robust performance. Further, horizon sensitivity analysis identifies a 12-week window as optimal for balancing responsiveness and profit stability. This research represents a pioneering effort in bridging the gap between probabilistic demand forecasting and policy optimization techniques, resulting in a practical tool that addresses the challenges of inventory management in an e-commerce setting, contributing to improved efficiency, reduced costs, and enhanced profitability.

Population-based epidemiological analysis of acute pyelonephritis and antibiotic prescription in Spain (2009–2018)

Objectives To estimate the incidence of pyelonephritis in primary care in Spain from 2009 to 2018, assess the associated antibiotic prescriptions, and analyse trends by sex and age. Method This is a retrospective observational population-based national study using the Database for Pharmacoepidemiological Research in the Public Domain (BIFAP), which contains primary care electronic medical records , and is representative of the Spanish population. Patients with a diagnosis of pyelonephritis were included. Sociodemographic and clinical data were collected. Crude and adjusted incidence rates were calculated per 10,000 person-years by sex and age, and annual and global percentages of antibiotic use were calculated by sex, age, and antibiotic group. Trend analysis was performed using a joinpoint regression model. Results 24,888 cases of pyelonephritis were recorded with an incidence of 4.2/10,000 person-years (6.6 women vs 1.5 men). An annual decreasing trend was observed in women (AAPC average annual percentage change) –2.7 (95% CI −4.4;-0.9), men −3.0 (95% CI −4.5;-1.5), patients aged 18–64 years −2.9 (95% CI −4.7;-0.9) and ≥ 65 years −4.2 (95% CI −5.8;-2.4). The most frequently used groups of antibiotics were cephalosporins (38.7%), quinolones (30%), combined penicillins (22.2%) and fosfomycin (6.8%). Cephalosporin prescription predominated in women (39.8%), and quinolone prescription in men (40.3%). The most prescribed cephalosporins were third and second generation (21% and 17.7% respectively). A downward annual trend was observed in the global use of antibiotics AAPC −0.8 (95% CI −1.4; −0.2), with an increasing AAPC 1.7 (95% CI −0.6; 3.4) in ≥65 years. Among the groups of antibiotics, the prescription of quinolones AAPC −6.9 (95% CI −31.7;17.3) and penicillins AAPC −8.7 (95% CI −11.2;-6.8) decreased and cephalosporins increased AAPC 19.0 (95% CI 12.2;26). Conclusions Women had a fourfold higher incidence of acute pyelonephritis than men, with a decreasing trend over the study period. Cephalosporins were the most commonly prescribed antibiotics in women, while quinolones were more common in men. An increasing trend in cephalosporin use and a decreasing in quinolone use were observed.

Inverse decoration of TiOx to NiSn alloy nanoparticles for efficient hydrodeoxygenation of m-cresol

Design of an intelligent IoT enabled healthcare responsive framework for emergency scenarios

Beyond trauma: Schema-driven psychological burden in psoriasis

Psoriasis is a chronic inflammatory skin disease with well-documented psychological comorbidities, yet the mechanisms linking early life experiences to its psychosocial impact remain underexplored. This cross-sectional study examined the associations between childhood trauma, early maladaptive schemas (EMSs), and psychological distress in adults with psoriasis (n = 85), other chronic illnesses (n = 85), and healthy controls (n = 85). Participants completed validated self-report measures assessing childhood maltreatment (Childhood Trauma Questionnaire–Short Form), EMSs (Young Schema Questionnaire–Short Form), and symptoms of depression, anxiety, and stress (Depression Anxiety Stress Scale). Statistical analysis revealed that, relative to healthy controls, the psoriasis group endorsed higher Emotional Deprivation, Insufficient Self-Control, and Emotional Inhibition schemas, consistent with enduring emotion regulation difficulties. Psoriasis patients also reported greater depression symptoms than healthy controls, and higher anxiety and stress than both healthy and chronically ill controls. Although no between-group differences emerged in retrospectively reported childhood trauma, the pattern of schema elevations suggests that difficulties in early emotional development, such as unmet emotional needs or subtle forms of neglect, may have contributed to later vulnerability, reflected at the schema rather than the trauma-report level. Overall, the findings highlight schema-level vulnerabilities in psoriasis that may underlie psychological distress and potentially contribute to symptom maintenance. Clinically, brief screening for EMSs and emotion-regulation problems in dermatological settings may support risk stratification and referral. Integrating schema-focused and stress-reduction interventions into routine psoriasis care could improve well-being and disease management.

Author Correction: Nanostructured organic sheets sequestering small extracellular vesicles and reactive species to protect against radiation-induced mucositis

Cross-range self-attention single hyperspectral image super-resolution method based on U-Net architecture

Deciphering the pathogenicity of three NKX2-1 variants in ultra-severe forms of childhood interstitial lung disease

Introduction The transcription factor NK2 homeobox1 (NKX2−1), associated with brain lung thyroid syndrome, regulates the transcription of surfactant proteins, thyroglobulin (TG) and thyroid peroxidase (TPO). This study explored the pathogenicity of three NKX2−1 variants (p.(Tyr214Cys), p.(Arg165Trp) and p.(Gly147Ala)) that were identified in three infants with lethal forms of childhood interstitial lung disease. Methods HEK293T cells were co-transfected with expression plasmids of NKX2−1 (wild-type (WT) and variants) and PAX8, along with reporter plasmids containing the promoters of SFTPB, SFTPC, TG and TPO ). Protein expression was analyzed by western blotting and immunofluorescence. Luciferase assays were performed to evaluate the activation of different promoters. Surfactant protein and NKX2−1 expression were also assessed on patient lung biopsies using immunohistochemistry. Results All three mutant proteins exhibited nuclear localization. Protein expression was altered in the p.(Tyr214Cys) and p.(Arg165Trp) variants located in NKX2.1 homeodomain. The p.(Tyr214Cys) variant failed to transactivate the tested promoters and was associated with a lack of pro-SP-C and SP-C expression in lung biopsy whereas the p.(Arg165Trp) variant induced both gain- or loss-of-function effects on the tested promoters. Finally, the p.(Gly147Ala) variant transactivated all the promoters tested, as for the WT. Conclusion: Our results demonstrated the pathogenicity of two variants, p.(Tyr214Cys) and p.(Arg165Trp), located within the homeodomain of NKX2−1. Conversely, the p.(Gly147Ala) variant showed no pathogenic effects. To date, the p.(Tyr214Cys) variant is associated with the most severe respiratory phenotype reported for NKX2–1-related disorders. Further studies are needed to understand the specific mechanisms underlying the pathogenicity of NKX2.1 variants located in the homeodomain.

Contrasting pathways to tree longevity in gymnosperms and angiosperms

Abstract Tree longevity is thought to increase in growth-limiting, adverse environments, but a quantitative assessment of drivers of global variation in tree longevity is lacking. We assemble a global database of maximum longevity for 739 tree species and analyse associations between longevity and climate, soil, and species’ functional traits. Our results show two primary pathways towards long lifespans. The first is slow growth in resource-limited environments, consistent with the “adversity begets longevity” paradigm. The second pathway is through relief from abiotic constraints in productive environments. Despite notable exceptions, long-lived gymnosperms tend to follow the first path through slow growth in cold environments, whereas long-lived angiosperms tend to follow the second (“productivity”) path reaching maximum longevity generally in humid environments. For angiosperms, we identify two mechanisms for increased longevity under humid conditions. First, higher water availability increases species’ maximum tree height which is associated with greater longevities. Secondly, greater water availability increases stand density and inter-tree competition, limiting growth which may increase tree lifespan. The documented differences between gymnosperm and angiosperm longevity are likely rooted in intrinsic differences in hydraulic architecture that provide fitness advantages for gymnosperms under high abiotic stress, and for angiosperms under increased productivity or competition.

Factors that affect distance-corrected near visual acuity in partial range of focus intraocular lenses

Depression and weight loss trajectories during an integrated behavioral intervention: Within-treatment analysis of the RAINBOW trial

Introduction Depression and obesity are two of the most common chronic conditions among US adults. The Research Aimed at Improving Both Mood and Weight (RAINBOW) study was the first randomized clinical trial to demonstrate the effectiveness of an integrated behavioral treatment for depression and obesity. We aimed to characterize the trajectories of both depression symptoms and weight loss during the RAINBOW intervention. Methods Participants (N = 201) randomly assigned to the RAINBOW treatment arm who provided serial data on depression symptoms (via the 9-item Patient Health Questionnaire [PHQ9]) and self-measured weight were included. Group-Based Multi-Trajectory Modeling is a statistical technique that identifies participants who follow similar trajectories of multiple outcomes over time. This approach was used to characterize latent groups of both PHQ9 and weight loss percentage during treatment. Demographic differences between groups were investigated using Chi-Square, Fisher’s exact tests, or ANOVA tests. Group membership was investigated for relationships with 12-month change in independently measured depression (via the 20-item Symptom Checklist, or SCL20) and weight (measured by trained research staff) using linear regression models. Results Participants were classified into 3 groups based on their depression symptom and weight trajectories: Moderate Depression Improvements/Minimal Weight Loss (N = 108, 53.7%), Substantial Depression Improvements/Moderate Weight Loss (N = 58, 28.9%), and Substantial Depression Improvements/Substantial Weight Loss (N = 35; 17.4%). Older participants were more likely to be in the Substantial/Substantial group. Participants in the Substantial/Moderate and Substantial/Substantial groups had larger 12-month depression symptom score changes and 12-month weight loss compared to the Moderate/Minimal group. Conclusion We identified three joint trajectories of depression symptom scores and obesity. Members in the three trajectories saw varying degrees of symptom reduction from baseline to 12 months. Results suggest adaptive treatment trials may be needed for participants in groups with lower anticipated depression symptom scores and/or weight reductions.

A versatile platform for chemical engineering of exosomes empowered by ADP-ribosyl cyclases

Abstract Cell-secreted exosomes have been emerging as an increasingly attractive form of nanomaterials for biomedical research. Various approaches have been established to genetically modify exosomes with proteins of interest for new and/or improved functions. However, equipping exosomes with diverse non-protein biomolecules remains largely dependent on random chemical conjugation or membrane insertion, hindering the application potential of exosomes. Herein, we develop a technology for site-specific functionalization of exosome with different synthetic groups by exploiting surface-expressed CD38, an ADP-ribosyl cyclase, and its covalent inhibitor derived from nicotinamide adenine dinucleotide (NAD + ). The designed ADP-ribosyl cyclase-enabled exosomes (ARC Exos) carrying conjugated fluorescent imaging probes, small-molecule ligands, cytotoxic payloads, and bone-targeting agents are demonstrated with in vitro and/or in vivo activities and specificities. This ARC Exos-based platform provides a general approach with great versatility for chemically reprogramming exosomes.

Optimization of ultrasound-assisted enzymatic extraction of saponins from Panax zingiberensis stems and leaves

Patient and guardian perspectives on tissue engineering in microtia reconstruction

Background Tissue Engineering (TE) is a newer technology with ongoing development across various areas of healthcare. For microtia patients, TE holds promise as a viable option for ear reconstruction, making it essential to understand the perspectives of patients and guardians. This study aimed to evaluate the perspectives of microtia patients and guardians, specifically investigating levels of awareness, comprehension, and interest in TE. Methods A survey and educational material were distributed to microtia patients and guardians. Surveyors were assessed on a Likert scale, and comparative analyses, including two-sample t-testing and multivariate analysis with logistic regression, were used to observe trends in responses. Results A total of 40 surveys were recorded. White patients reported greater familiarity with TE. More than half of the respondents expressed an interest in TE as a reconstructive option. Having a doctor provide TE information positively correlated with willingness to adopt TE reconstruction. Understanding of TE positively correlated with willingness to pursue TE for reconstruction. Patients with more severe grade microtia and white patients were more likely to travel to a hospital that offered TE. Conclusions We found that TE is an unfamiliar concept for most patients. Demographic, socioeconomic, cost, and trust in a doctor played an essential role in patients’ and guardians’ willingness to choose TE for microtia reconstruction. As TE for reconstruction approaches clinical use, these key considerations from a patient and family-centered lens about TE-based reconstruction is critical for application.

Peptidyl-tRNA hydrolase 2 is a negative regulator of peripartum cardiomyopathy with heart failure in female mice

Direct evidence of active tectonics along the offshore sector of the Dinaric Fault System

Abstract Tectonic deformation along the External Dinarides fold-and-thrust belt is slow, with transpressional crustal strain redistributed along multiple faults. Some of these faults reach the surface along the NE Adriatic coast as part of the strike-slip Dinaric Fault System (DFS). This work uses new high-resolution sub-bottom seismic data to characterize the geodynamic significance of active surface deformation in the offshore sector of the Kvarner area, Croatia. Seismic profiles reveal gentle folding in early Quaternary strata that is associated with contractional deformation in the Rijeka Bay; yet, active faults are documented only in narrow zones along the DFS, and specifically in the Vinodol and Velebit channels. Fault Mechanism Solutions (FMS) confirm that a strike-slip tectonic regime exists in the study area, but the strike of surface faults and FMS data are discrepant, probably as a result of strain dissipation along (creeping? ) faults whose geodynamic response differs from deep-rooted seismogenic structures. This differing geodynamic response causes important caveats when linking surface deformation to deeper seismogenic structures which are, offshore Kvarner, either blind structures or currently deforming under distinct stress conditions to near-surface faults. Crucially, this work presents the first geological evidence for active faulting along the DFS in Croatia, a piece of information deemed critical for future geohazard assessments.

Effects of intention understanding and brief imitative experience on the mirror neuron system: An EEG study using Japanese sign language

The mirror neuron system (MNS) is the neural system that activates when individuals both observe and execute an action. Previous studies consistently indicate that the MNS is also involved in intention understanding. In addition, MNS activity is augmented after imitating an unfamiliar action. However, it remains unclear whether conscious effort to interpret an actors’ intention further activates the MNS, consequently promoting action learning. To investigate an interactive effect between intention understanding and imitative experience of unfamiliar actions, the present study measured EEG while participants observed Japanese sign language and while they imitated signing. To manipulate a level of intention understanding, we prepared two tasks: the counting task required participants to count the number of body movements in sign language, and the meaning task required participants to guess the meaning of sign language. Mu suppression, one of the indices of the MNS, was measured during three phases: pre-imitation, imitation, and post-imitation. The results revealed that the magnitude of mu suppression was comparable between the two tasks, and remained unchanged in the pre- and post-imitation phases. The null effect of the imitative experience may be attributable to cultural factors as gestural communication is less encouraged in Japanese culture, making it challenging for the MNS to learn new actions. Furthermore, absence of an effect from the task may be attributed to greater number of unfamiliar movements in sign language, resulting in the MNS preferentially processing body movements rather than the intention of actors.

Emergent collective alignment gives competitive advantage to longer cells during range expansion

Development of a laboratory-scale apparatus and experimental investigation of fluid property effects on pipe wear in slurry shield TBM operations

Evaluating the efficacy of intragastric botulinum toxin a injections with two different quantities and sites for obesity

Introduction Intragastric injections of botulinum toxin A (BTX-A) have shown promise in aiding weight reduction among obese patients, with a favorable safety profile and minimal adverse effects; however, the inconsistent results from prior studies highlight the need to examine key factors in the research of intragastric injection of botulinum toxin A, such as the dosage of BTX-A, the number and placement of injections. This study examines the efficacy of varying high doses, multi-gastric sites botulinum toxin A injections for weight control. Materials and Methods A total of 103 patients aged 18–65 with a BMI ≥ 25 kg/m² were assigned to four groups receiving endoscopic BTX-A injections at varying doses and sites: Group 1 (400 IU, fundus and body), Group 2 (300 IU, fundus and body), Group 3 (400 IU, antrum and body), and Group 4 (300 IU, antrum and body). Baseline comparisons used ANOVA, while a mixed model assessed the interaction among injection site, dose, and time on outcomes. Results Baseline measures showed no group differences in bodyweight, BMI, or body fat. The mixed model indicated significant reductions in bodyweight, BMI, and body fat with gastric fundus and body injections. Site and dose interactions significantly affected bodyweight (p = 0.024) and body fat (p = 0.041), but not BMI. Conclusions Endoscopic intragastric BTX-A injections effectively reduce body weight, BMI, and body fat, particularly with injections in the fundus and body regions.