Psoriasis localization patterns in the Swiss Psoriasis Registry (SDNTT) over 11 years: an analysis by sex and age.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals.

Correlation of Clinical Severity of Trachomatous Inflammation and Chlamydia trachomatis Bacterial Load.

The purpose of this study was to investigate the correlation between bacterial load of Chlamydia trachomatis as measured from quantitative polymerase chain reaction (qPCR) and the relative clinical severity of trachomatous inflammation. Individuals with trachoma from rural communities in Ethiopia had photographs taken as well as swabs obtained of the upper tarsal conjunctivas. Conjunctival swabs were processed with PCR assay, which provided quantitative results of ocular chlamydial load. A series of 125 conjunctival photographs were ranked from least to most severe according to clinical severity for follicular and papillary conjunctivitis. Higher intensity rankings of trachomatous inflammation were associated with higher chlamydial load for both follicular inflammation (Spearman's ρ = 0.43; P <0.001) and papillary inflammation (Spearman's ρ = 0.50; P <0.001). Rankings of trachomatous inflammation may be a clinically meaningful indicator of trachoma.

Descemet Endothelial Thickness Comparison Trial II (DETECT II): multicentre, outcome assessor-masked, placebo-controlled trial comparing Descemet membrane endothelial keratoplasty (DMEK) to Descemet stripping only (DSO) with adjunctive ripasudil for Fuchs dystrophy.

INTRODUCTION: It remains uncertain whether Descemet membrane endothelial keratoplasty (DMEK) or Descemet stripping only (DSO) yields better outcomes in patients with symptomatic Fuchs endothelial corneal dystrophy (FECD). This paper presents the protocol for the Descemet Endothelial Thickness Comparison Trial II (DETECT II), a multicentre, outcome-masked, randomised, placebo-controlled, clinical trial comparing DMEK to DSO with ripasudil (DSO-R) for this patient population. METHODS AND ANALYSIS: A total of 60 patients with endothelial dysfunction due to symptomatic FECD will be enrolled from seven participating sites in the USA. The patients will be randomly assigned in a 1:1 ratio to one of the following treatment groups: group 1-DMEK plus topical placebo and group 2-DSO plus topical ripasudil 0.4%. The enrolment period is 24 months. The primary outcome is best spectacle-corrected visual acuity at 12 months. Secondary outcomes include peripheral and central endothelial cell density, visual acuity, vision-related quality of life and Pentacam Scheimpflug tomography. Study outcomes will be analysed using mixed effects linear regression. Adverse events, including rebubble procedures, endothelial failure and graft rejection, will be documented and analysed using appropriate statistical methods. DETECT II aims to provide evidence on the comparative effectiveness of DMEK and DSO-R. The results of this trial will contribute to optimising the treatment of FECD, while also exploring the cost-effectiveness of these interventions. Dissemination of findings through peer-reviewed publications and national/international meetings will facilitate knowledge translation and guide clinical practice in the field of corneal transplantation. ETHICS AND DISSEMINATION: A data and safety monitoring committee has been empanelled by the National Eye Institute. All study protocols will be subject to review and approval by WCG IRB as the single IRB of record. This study will comply with the National Institute of Health (NIH) Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Data from the trial will be made available on reasonable request. TRIAL REGISTRATION NUMBER: NCT05275972.

Transitioning Adolescents and Young Adults with Lipid Disorders to Adult Health Care.

PURPOSE OF REVIEW: Pediatric healthcare providers have increasingly become aware of the need for timely and informative transition of adolescents and young adults with chronic medical conditions such as diabetes and cystic fibrosis. However, there is paucity of published data on the importance of and most effective way to transition youth with lipid disorders who are at increased risk of premature cardiovascular disease. RECENT FINDINGS: Evidence shows that atherosclerosis begins at a young age. However, there are no guidelines on the transition of adolescents and young adults with dyslipidemia. In addition, there are conflicting guidelines for lipid management in children versus adults, despite advances in medical pharmacotherapies for dyslipidemia. The lack of guidelines for transition and discordant recommendations for management of this vulnerable population places young adults at-risk for worsening of their underlying disease, and premature cardiovascular events.

CelltypeR: A flow cytometry pipeline to characterize single cells from brain organoids.

Motivated by the cellular heterogeneity in complex tissues, particularly in brain and induced pluripotent stem cell (iPSC)-derived brain models, we developed a complete workflow to reproducibly characterize cell types in complex tissues. Our approach combines a flow cytometry (FC) antibody panel with our computational pipeline CelltypeR, enabling dataset aligning, unsupervised clustering optimization, cell type annotating, and statistical comparisons. Applied to human iPSC derived midbrain organoids, it successfully identified the major brain cell types. We performed fluorescence-activated cell sorting of CelltypeR-defined astrocytes, radial glia, and neurons, exploring transcriptional states by single-cell RNA sequencing. Among the sorted neurons, we identified subgroups of dopamine neurons: one reminiscent of substantia nigra cells most vulnerable in Parkinson's disease. Finally, we used our workflow to track cell types across a time course of organoid differentiation. Overall, our adaptable analysis framework provides a generalizable method for reproducibly identifying cell types across FC datasets in complex tissues.

Neurologic Clinical, Electrophysiologic, and Pathologic Characteristics of Primary vs Secondary Neurolymphomatosis.

BACKGROUND AND OBJECTIVES: Neurolymphomatosis (NL) is characterized by lymphomatous infiltration of the peripheral nervous system presenting as the initial manifestation of a lymphoma (primary NL [PNL]) or in relapse of a known lymphoma (secondary NL [SNL]). This report details and compares the neurologic clinicopathologic characteristics of these 2 groups. METHODS: This retrospective study was performed on patients diagnosed with pathologically confirmed NL in nerve between January 1, 1992, and June 31, 2020. Patient clinical characteristics, neurologic examination, imaging studies, EMG, and nerve biopsy data were collected, analyzed, and compared between PNL and SNL. RESULTS: A total of 58 patients were identified (34 PNL and 24 SNL). Time from neurologic symptom onset to diagnosis was longer in PNL at 18.5 months compared with 5.5 months in SNL (p = 0.01). Neurologic symptoms were similar in both patient groups and included primarily sensory loss (98%), severe pain (76%), and asymmetric weakness (76%). A wide spectrum of EMG-confirmed different neuropathy patterns were observed, but patients with SNL had increased numbers of mononeuropathies (n = 8) compared with PNL (n = 1, p = 0.01). MRI studies detected NL more frequently (86%) compared with fluorodeoxyglucose (FDG)-PET CT imaging studies (60%) (p = 0.007). Nerve biopsies revealed B-cell lymphoma (PNL n = 32, SNL n = 22), followed by T-cell lymphoma (PNL n = 2, SNL n = 2), with increased demyelination in both groups and increased axonal degeneration (p = 0.01) and multifocal myelinated fiber loss (p = 0.04) significant in SNL vs PNL. Identifying SNL resulted in patient treatment modifications but a worse prognosis compared with PNL (p = 0.025). DISCUSSION: While PNL and SNL are both primarily painful and asymmetric neuropathies with axonal and demyelinating features on EMG and nerve biopsy, SNL presents somewhat differently than PNL with fulminant, asymmetric often mononeuropathies better detected on MRI than FDG-PET/CT. The focal pattern of SNL is likely a result of residual cancer cells that evaded initial chemotherapy, which does not cross the blood-nerve barrier, and these cells can later recur and result in fulminant disease. Although still resulting in a poorer prognosis, identifying SNL is important because this changed treatment and management in every SNL case.

Do longer duration nonclinical toxicology studies provide predictive clinical safety value? The IQ consortium longer duration nonclinical to clinical translational database.

The IQ Consortium's DruSafe Leadership Group previously reported results of a nonclinical to clinical translational database for First-In-Human (FIH)-enabling animal toxicology studies. We have completed an additional translational database populated with longer duration (>1 month) animal toxicology studies and longer duration (Phase 2 and beyond) clinical trials. The blinded database was composed of 127 molecules. Animal and clinical data were categorized by organ system and animal model (e.g. rodent, dog). The 2 × 2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis and both the positive predictive value (PPV) and negative predictive value (NPV) were determined. As also reported in the FIH database, the NPV was the strongest predictive performance measure at 96 %. The PPV was lower than the FIH database with the rodent at 29 %, dog at 21 % and NHP at 20 %. No new additional target organs were observed in 62 % of the entries. A new target organ was identified in 38 % of the entries, with the majority in a rodent (26 %) and fewer in the dog (8 %) or NHP (12 %). However, new target organ data resulted in only a PPV of 13 %, suggesting that current ICH requirements for longer duration animal general toxicology studies should be re-evaluated and better aligned with the 3Rs. A newer paradigm could include an appropriately justified single animal model for longer duration studies, in addition to utilizing New Approach Methods (NAMs) that would provide translational safety data, but additional research is needed.

Rapid discovery and evolution of nanosensors containing fluorogenic amino acids.

Binding-activated optical sensors are powerful tools for imaging, diagnostics, and biomolecular sensing. However, biosensor discovery is slow and requires tedious steps in rational design, screening, and characterization. Here we report on a platform that streamlines biosensor discovery and unlocks directed nanosensor evolution through genetically encodable fluorogenic amino acids (FgAAs). Building on the classical knowledge-based semisynthetic approach, we engineer ~15 kDa nanosensors that recognize specific proteins, peptides, and small molecules with up to 100-fold fluorescence increases and subsecond kinetics, allowing real-time and wash-free target sensing and live-cell bioimaging. An optimized genetic code expansion chemistry with FgAAs further enables rapid (~3 h) ribosomal nanosensor discovery via the cell-free translation of hundreds of candidates in parallel and directed nanosensor evolution with improved variant-specific sensitivities (up to ~250-fold) for SARS-CoV-2 antigens. Altogether, this platform could accelerate the discovery of fluorogenic nanosensors and pave the way to modify proteins with other non-standard functionalities for diverse applications.

Renal Solitary Fibrous Tumor With Müllerian Cysts: A Novel Differential Diagnosis for Biphasic Renal Neoplasms.

Solitary fibrous tumor is an uncommon mesenchymal neoplasm, initially described in the pleura and infrequently found in the kidney. It is characterized by haphazardly arranged spindle cells, staghorn vasculature, coexpression of CD34 and signal transducer and activator of transcription 6 (STAT6), and a NAB2::STAT6 gene fusion. We report a 64-year-old woman who presented with a 2.5 cm multilocular cystic renal mass. On microscopic examination, the tumor consisted of a spindle cell component closely intermingled with ciliated and hemorrhagic epithelial cysts. The spindle cell component was positive for CD34, B-cell lymphoma 2 (BCL2), and STAT6, confirming the diagnosis of a solitary fibrous tumor. The epithelial cysts expressed keratin 7, PAX8, BCL2, estrogen receptor 1, and progesterone receptor, indicative of Müllerian cysts. The occurrence of solitary fibrous tumor in the kidney is extremely rare, and its association with Müllerian cysts has not been previously reported in the kidney. This morphologic variant has a striking similarity with biphasic renal neoplasms, especially with mixed epithelial and stromal tumors and angiomyolipoma with epithelial cysts. This report describes a novel renal solitary fibrous tumor subtype within this differential and underscores clinical and pathological distinctions of biphasic renal neoplasms.

Spatially Varying Wolbachia Frequencies Reveal the Invasion Origin of an Agricultural Pest Recently Introduced From Europe to North America.

The introduction of non-native species across the world represents a major global challenge. Retracing invasion origin is an important first step in understanding the invasion process, often requiring detailed sampling within the native range. Insect species frequently host Wolbachia, a widespread endosymbiotic bacterium that manipulates host reproduction to increase infected female fitness. Here, we draw on the spatial variation in infection frequencies of an actively spreading Wolbachia strain wCer2 to investigate the invasion origin of the European cherry fruit fly, Rhagoletis cerasi. This pest of cherries was introduced from Europe to North America within the last decade. First, we screen the introduced fly population for the presence of Wolbachia. The introduced populations lack the wCer2 strain and the strongly associated mitochondrial haplotype, suggesting strain absence due to founder effects with invading individuals originating from wCer2-uninfected native population(s). To narrow down geographic regions of invasion origin, we perform spatial interpolation of the wCer2 infection frequency across the native range and predict the infection frequency in unsampled regions. For this, we use an extensive dataset of R. cerasi infection covering 238 populations across Europe over 25 years, complemented with 14 additional populations analyzed for this study. We find that R. cerasi was unlikely introduced from wCer2-infected populations in Central and Western Europe. We propose wCer2-uninfected populations from Eastern Europe and the Mediterranean region as the most likely candidates for the invasion origin. This work utilizes Wolbachia as an indirect instrument to provide insights into the invasion source of R. cerasi in North America, revealing yet another application for this multifaceted heritable endosymbiont. Given the prevalence of biological invasions, rapidly uncovering invasion origins gives fundamental insights into how invasive species adapt to new environments.

Computer Vision Identification of Trachomatous Inflammation-Follicular Using Deep Learning.

PURPOSE: Trachoma surveys are used to estimate the prevalence of trachomatous inflammation-follicular (TF) to guide mass antibiotic distribution. These surveys currently rely on human graders, introducing a significant resource burden and potential for human error. This study describes the development and evaluation of machine learning models intended to reduce cost and improve reliability of these surveys. METHODS: Fifty-six thousand seven hundred twenty-five everted eyelid photographs were obtained from 11,358 children of age 0 to 9 years in a single trachoma-endemic region of Ethiopia over a 3-year period. Expert graders reviewed all images from each examination to determine the estimated number of tarsal conjunctival follicles and the degree of trachomatous inflammation-intense. The median estimate of the 3 grader groups was used as the ground truth to train a MobileNetV3 large deep convolutional neural network to detect cases with TF. RESULTS: The classification model predicted a TF prevalence of 32%, which was not significantly different from the human consensus estimate (30%; 95% confidence interval of difference, -2 to +4%). The model had an area under the receiver operating characteristic curve of 0.943, F1 score of 0.923, 88% accuracy, 83% sensitivity, and 91% specificity. The area under the receiver operating characteristic curve increased to 0.995 when interpreting nonborderline cases of TF. CONCLUSIONS: Deep convolutional neural network models performed well at classifying TF and detecting the number of follicles evident in conjunctival photographs. Implementation of similar models may enable accurate, efficient, large-scale trachoma screening. Further validation in diverse populations with varying TF prevalence is needed before implementation at scale.

Learning, internalisation and integration of the COVID-19 pandemic in healthcare workers: A qualitative document analysis.

The COVID-19 pandemic triggered an unprecedented health crisis that impacted healthcare systems worldwide. This study explores how Spanish healthcare workers learned, internalised and integrated values and work behaviours during the COVID-19 pandemic and their impact on the personal sphere. This documentary research, using images, narratives and audiovisual content, was framed within the interpretative hermeneutic paradigm. Categories and subcategories emerged after a final theoretical sampling that focused on the analysis. Data triangulation between researchers favoured theoretical saturation. A total of 117 images and 27 texts were selected. The analysis identified three stages: bewilderment, seeking functionality in the chaos and integrating chaos into care. The data reflects how the need for security and knowledge, and the exhaustion and frustration caused by the initial working conditions, prompted adaptive responses. These responses involved focusing on problem-solving and strengthening group sentiments and solidarity. Subsequently, the data indicates the acceptance of new structural, organisational and communication aspects. The findings of the analysis will contribute towards finding a framework that can help understand community health crisis events.

Thirteen-Year Follow-Up of Conjunctival Amyloidosis.

This case report discusses a diagnosis of conjunctival amyloidosis in an otherwise asymptomatic male aged 71 years with 13-year follow-up.

Impact of seizure outcome and extent of neocortical resection on emotional well-being in patients with epilepsy one year after temporal lobe surgery.

BACKGROUND: Seizure frequency and cognitive function are common parameters in assessing epilepsy surgery outcomes. However, psychobehavioral outcomes, such as symptoms of depression and quality of life (QOL), have not found equal attention yet. OBJECTIVE: To assess the effect of seizure frequency, the extent of resection, and cognitive function on the psychobehavioral outcome of patients after temporal lobe surgery for pharmacoresistant epilepsy. METHODS: We retrospectively reviewed all consecutive patients who underwent surgery for intractable temporal lobe epilepsy between 09/2015 and 07/2019. We examined seizure outcome, surgical plan, resection volume, cognitive functions, and psychobehavioral outcome. RESULTS: This study included 77 patients (31 males, 46 females) who underwent temporal lobe surgery. One year after surgery, 53 patients (68.8 %) were completely seizure-free (Engel IA) and 92.2 % of patients showed a worthwhile improvement in seizure frequency (Engel I-III). Resection volume was significantly negatively correlated with QOL (r =  - 0.284, p = 0.041). However, after controlling for the effect of seizure outcome, no significant correlation remained. Patients with a worthwhile improvement in seizure frequency showed significantly fewer symptoms of depression (p = 0.024) and a significantly higher QOL (p = 0.012) one year after surgery. The differences in symptoms of depression (p = 0.044) and QOL (p = 0.030) between patients with and without improvements in seizure frequency remained significant after controlling for the effect of resection volume. After procedures sparing the amygdala and hippocampus (neocortical resection), patients presented significantly fewer symptoms of depression (p = 0.044) and significantly better QOL (p = 0.008) than patients after procedures involving mesial-temporal structures, independent of the resection volume, and after controlling for the side of the procedure (dominant vs. non-dominant). After also controlling for seizure outcome, the difference remained for QOL (p = 0.014) but not for symptoms of depression. CONCLUSIONS: A patient's emotional well-being one year after surgery for pharmacoresistant temporal lobe epilepsy strongly depends on their seizure outcome. As an individual factor, the extent of neocortical resection negatively affects postsurgical emotional well-being, but a favorable seizure outcome outweighs this effect, independent of the resection volume. A favorable seizure outcome even outweighs the negative effects of procedures involving mesial-temporal structures on symptoms of depression.

Multitarget Ligands that Comprise Opioid/Nonopioid Pharmacophores for Pain Management: Current State of the Science.

Chronic pain, which affects more than one-third of the world's population, represents one of the greatest medical challenges of the 21st century, yet its effective management remains sub-optimal. The 'gold standard' for the treatment of moderate to severe pain consists of opioid ligands, such as morphine and fentanyl, that target the µ-opioid receptor (MOP). Paradoxically, these opioids also cause serious side effects, including constipation, respiratory depression, tolerance, and addiction. In addition, the development of opioid-use disorders, such as opioid diversion, misuse, and abuse, has led to the current opioid crisis, with dramatic increases in addiction, overdoses, and ultimately deaths. As pain is a complex, multidimensional experience involving a variety of pathways and mediators, dual or multitarget ligands that can bind to more than one receptor and exert complementary analgesic effects, represent a promising avenue for pain relief. Indeed, unlike monomodal therapeutic approaches, the modulation of several endogenous nociceptive systems can often result in an additive or even synergistic effect, thereby improving the analgesic-to-side-effect ratio. Here, we provide a comprehensive overview of research efforts towards the development of dual- or multi-targeting opioid/nonopioid hybrid ligands for effective and safer pain management. We reflect on the underpinning discovery rationale by discussing the design, medicinal chemistry, and in vivo pharmacological effects of multitarget antinociceptive compounds.

Discovery of VU6016235: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM).

Herein, we report structure-activity relationship (SAR) studies to develop novel tricyclic M4 PAM scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace a 5-amino-2,4-dimethylthieno[2,3-d]pyrimidine-6-carboxamide core, which led to the discovery of two novel tricyclic cores. While both tricyclic cores displayed low nanomolar potency against both human and rat M4 and were highly brain-penetrant, the 2,4-dimethylpyrido[4',3':4,5]thieno[2,3-d]pyrimidine tricycle core provided lead compound, VU6016235, with an overall superior pharmacological and drug metabolism and pharmacokinetics (DMPK) profile, as well as efficacy in a preclinical antipsychotic animal model.

Cause-Specific Mortality among Infants in a Randomized Controlled Trial of Azithromycin Compared to Placebo for Prevention of Mortality.

Although community randomized trials have found a reduction in all-cause child mortality in communities receiving mass azithromycin distribution compared with placebo, individually randomized trials have not found similar protective effects. If a direct effect of azithromycin for prevention of child mortality exists, it is likely due to reduction in infectious mortality. Here, we assessed cause-specific mortality in a large randomized controlled trial of azithromycin administered during well-infant visits in Burkina Faso for prevention of mortality. Among 32,877 enrolled infants, the most common causes of death by 6 months of age were malaria, acute respiratory infections, and diarrheal disease. We found no evidence of a difference in the distribution of cause of death by randomized treatment assignment (P = 0.42) or in any infectious-specific cause of death. The results of this analysis are consistent with no direct effect of azithromycin on infant mortality when administered during well-infant visits.

Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review.

PURPOSE: Optimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols. METHODS: A systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted. RESULTS: Out of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14-52%; 3-16% were muscle-invasive while 11-36% were non-muscle invasive. Nodal recurrence occurred at 13-16% and distant metastases at 15-35%. After 5 and 10 years of follow-up, around 60-85% and 45-75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar. CONCLUSION: Randomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.

Optimizing the fermentation parameters in the Lactic Acid Fermentation of Legume-based Beverages- a statistically based fermentation.

BACKGROUND: The market for beverages is highly changing within the last years. Increasing consumer awareness towards healthier drinks led to the revival of traditional and the creation of innovative beverages. Various protein-rich legumes were used for milk analogues, which might be also valuable raw materials for refreshing, protein-rich beverages. However, no such applications have been marketed so far, which might be due to unpleasant organoleptic impressions like the legume-typical "beany" aroma. Lactic acid fermentation has already been proven to be a remedy to overcome this hindrance in consumer acceptance. RESULTS: In this study, a statistically based approach was used to elucidate the impact of the fermentation parameters temperature, inoculum cell concentration, and methionine addition on the fermentation of lupine- and faba bean-based substrates. A total of 39 models were found and verified. The majority of these models indicate a strong impact of the temperature on the reduction of aldehydes connected to the "beany" impression (e.g., hexanal) and on the production of pleasantly perceived aroma compounds (e.g., ß-damascenone). Positively, the addition of methionine had only minor impacts on the negatively associated sulfuric compounds methional, dimethyl sulfide, dimethyl disulfide, and dimethyl trisulfide. Moreover, in further fermentations, the time was added as an additional parameter. It was shown that the strains grew well, strongly acidified the both substrates (pH ≤ 4.0) within 6.5 h, and reached cell counts of > 9 log10 CFU/mL after 24 h. Notably, most of the aldehydes (like hexanal) were reduced within the first 6-7 h, whereas pleasant compounds like ß-damascenone reached high concentrations especially in the later fermentation (approx. 24-48 h). CONCLUSIONS: Out of the fermentation parameters temperature, inoculum cell concentration, and methionine addition, the temperature had the highest influence on the observed aroma and taste active compounds. As the addition of methionine to compensate for the legume-typical deficit did not lead to an adverse effect, fortifying legume-based substrates with methionine should be considered to improve the bioavailability of the legume protein. Aldehydes, which are associated with the "beany" aroma impression, can be removed efficiently in fermentation. However, terminating the process prematurely would lead to an incomplete production of pleasant aroma compounds.