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Adolescent food insecurity is a salient adversity hypothesized to affect neural systems associated with increased impulsive behavior. Family environments shape how adverse experiences influence development. In this study, hypotheses were tested regarding the conjoint effects of food insecurity and family flexibility on impulsivity via alterations in connectivity between regions within the salience and central executive networks. Such alterations are reflected in resting‐state functional connectivity (rsFC) metrics between the anterior insula (AI) and the middle frontal gyrus (MFG). Hypotheses were tested in a longitudinal moderated mediation model with two waves of data from 142 adolescents (Time 1 [T1] Mage = 12.89, SD = 0.85; Time 2 [T2] Mage = 15.01, SD = 1.07). Data on past‐year household food insecurity, family flexibility, and rsFC were obtained at T1. Impulsivity was self‐reported by the adolescent at T1 and T2. Findings revealed that high T1 left‐to‐left rsFC between the AI and MFG was associated with increased impulsivity at T2. The interaction of family flexibility and food insecurity was associated with AI and MFG rsFC. In the context of low family flexibility, food insecurity was linked to high levels of AI and MFG rsFC. Conversely, in the context of optimal family flexibility, food insecurity was associated with low levels of AI and MFG rsFC. Conditional indirect analysis suggests that the links among food insecurity, rsFC, and impulsive behavior depend on family flexibility. Research Highlights: Adolescent food insecurity was associated with anterior insula and middle frontal gyrus connectivity only at certain levels of family flexibility.High family flexibility attenuated the link between food insecurity and neural connectivity, while low levels of family flexibility increased this risk.High left anterior insula and left middle frontal gyrus connectivity was associated with increased impulsivity 1 year later. [ABSTRACT FROM AUTHOR]

Summary: During the primary fermentation of beer, the yeast simultaneously carries out a series of processes such as cell growth, pH shift, and the formation and degradation of essential flavour components. Harvested yeast from a previous fermentation can be used to inoculate the fermentation or fresh cells can be produced through aerobic propagation. This study investigated the influence of different aeration conditions during Saccharomyces pastorianus ssp. carlsbergensis propagation on the cell count development and the production of secondary metabolites during the subsequent primary beer fermentation. Propagations were conducted by applying six different dissolved oxygen concentrations, and the cells were used as inoculum for the subsequent fermentation. Cell count, pH shift, and the development of key aroma compounds were monitored throughout the primary fermentation to evaluate any difference between the conducted fermentations. The outcomes revealed significant distinctions between fermentations using yeast propagated under elevated oxygen levels and those propagated under reduced oxygen levels. Cells propagated using lower oxygen concentrations showed earlier cell growth with 40% lower final cell counts, resulting in 50% reduced biomass yields. Additionally, lower oxygen concentrations during propagation led to lower pH shifts during primary fermentation with 20% more higher alcohols and elevated formation of acetaldehyde, and esters. [ABSTRACT FROM AUTHOR]

Background: Permanent tattooing is the invasive introduction of tattoo ink (pigments) into the dermis. The ink and aftercare cosmetics applied on pre‐damaged skin may contain skin sensitisers. Objectives: To identify patient characteristics and the pattern of sensitisation in tattooed patients patch tested within the Information Network of Departments of Dermatology (IVDK). Patients and Methods: Comparative analysis of patient characteristics and reaction frequencies to baseline series allergens in 1648 consecutive patients with and 8045 consecutive patients without permanent tattoos. Non‐overlapping 95%‐confidence intervals were considered as significant. Results: Having permanent tattoos was related with female sex, age <40 years, tobacco smoking, atopic dermatitis, (occupational) hand dermatitis and being employed in particular occupational groups (e.g., healthcare workers, mechanics, hairdressers). Sensitisation to nickel was increased in tattooed patients and associated with female sex (OR 4.23 [95%‐CI, 3.48–5.18]), age ≥40 years (OR 1.26 [95%‐CI, 1.08–1.49]), tobacco smoking (OR 1.19 [95%‐CI, 1.01–1.40]) and having permanent tattoos (OR 1.27 [95%‐CI, 1.05–1.53]). Conclusions: The association between nickel sensitisation and permanent tattoos is probably confounded by past reactions to pierced costume jewellery. Socio‐economic factors most probably contribute to the connection between tattoos, tobacco smoking, occupational or hand dermatitis, and being employed in particular occupational groups. [ABSTRACT FROM AUTHOR]

Background: Earlier studies suggested a potential association between tobacco smoking and nickel sensitization, but little is known about other contact allergens. Objectives: To investigate the association of smoking status and contact sensitizations as well as subtypes of dermatitis, and to analyse the sensitization profiles of tobacco smokers. Patients and Methods: Within the Information Network of Departments of Dermatology (IVDK), we performed a cross‐sectional multicentre pilot study comprising 1091 patch‐tested patients from 9 departments, comparing 541 patients with a history of cigarette smoking (281 current and 260 former smokers) with 550 never‐smokers. Results: We could not confirm the previously reported association between nickel sensitization and tobacco smoking. Moreover, sensitizations to other allergens, including colophony, fragrance mix I, Myroxylon pereirae and formaldehyde, were not increased in cigarette smokers compared with never smokers. Hand dermatitis (50.6% vs. 33.6%) and occupational cause (36.2% vs. 22.5%) were significantly more frequent among cigarette smokers compared with never‐smokers as shown by non‐overlapping 95% confidence intervals. Conclusions: Although our study does not allow a firm conclusion on whether smoking status contributes to certain contact sensitizations, it confirms an association of smoking with hand dermatitis and occupational cause. [ABSTRACT FROM AUTHOR]

Polypropylene (PP) recyclates face limitations in their use due to lower qualities compared with virgin PP, resulting from contaminations and the mixing of different PP grades. In particular, their high melt flow rate (MFR) hinders their suitability for applications requiring low MFR, such as pipes. This study investigates the feasibility of producing low MFR PP recyclates from packaging waste. For this purpose, recyclates were produced exclusively from manually sorted extrusion blow molding grades and compared with a recyclate derived from a conventional PP waste stream. Different washing temperatures and recyclate production processes were used to study their effects on the properties of the recyclates. The main objective was to determine the lowest achievable MFR and the rheological, mechanical, and thermal properties of the recyclates from improved sorting. The results are intended to serve as reference points for the evaluation of future automatic sorting trials. The enhanced sorting resulted in an 80% reduction in the MFR and improved ductility, thereby extending the potential applications of the recyclate. The different washing and production processes did not have a significant effect on the investigated properties, except for a slight decrease in the MFR with hot washing and the omission of the pelletizing step. [ABSTRACT FROM AUTHOR]

Traumatic, life‐threatening events are experienced commonly among the general U.S. population, yet Black individuals in the United States (i.e., Black Americans) exhibit higher prevalence rates of posttraumatic stress disorder (PTSD) and more severe symptoms than other populations. Although empirical research has noted a range of symptom patterns that follow traumatic injury, minimal work has examined the role of racial discrimination in relation to PTSD symptom trajectories. The current study assessed racial discrimination and PTSD symptom trajectories at 6 months postinjury across two separate samples of traumatically injured Black Americans (i.e. emergency department (ED)–discharged and hospitalized). Identified PTSD symptom trajectories largely reflect those previously reported (i.e., ED: nonremitting, moderate, remitting, and resilient; hospitalized: nonremitting, delayed, and resilient), although the resilient trajectory was less represented than expected given past research (ED: 55.8%, n = 62; hospitalized: 46.9%, n = 38). Finally, higher racial discrimination was associated with nonremitting, ED: relative risk ratio (RR) = 1.32, hospitalized: RR = 1.23; moderate, ED: RR = 1.18; and delayed, hospitalized: RR = 1.26, PTSD symptom trajectories. Overall, the current findings not only emphasize the inimical effects of racial discrimination but also demonstrate the unique ways in which race‐related negative events can impact PTSD symptom levels and recovery across time. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early‐onset Alzheimer's disease (EOAD). METHODS: We examined single‐cell RNA‐sequencing (scRNA‐seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital polymerase chain reaction (ddPCR) data from CD4 T cells from participants with EOAD and clinically normal controls. RESULTS: We analyzed PBMCs from 16 individuals by scRNA‐seq and discovered increased interferon signaling‐associated gene (ISAG) expression and striking expansion of antiviral‐like ISAGhi T cells in EOAD. Isolating CD4 T cells from 19 individuals, including four cases analyzed by scRNA‐seq, we confirmed increased expression of ISAGhi marker genes. Publicly available cerebrospinal fluid leukocyte scRNA‐seq data from late‐onset mild cognitive impairment and AD also revealed increased expression of interferon‐response genes. DISCUSSION: Antiviral‐like ISAGhi T cells are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted. Highlights: Interferon‐responsive T cells expanded in early‐onset Alzheimer's disease (AD).Increased interferon‐associated gene expression present in early‐ and late‐onset AD.Peripheral immune changes in T and NK cells driven by females with early‐onset AD. [ABSTRACT FROM AUTHOR]

Splice-switching oligonucleotides (SSOs) are antisense compounds that act directly on pre-mRNA to modulate alternative splicing (AS). This study demonstrates the value that artificial intelligence/machine learning (AI/ML) provides for the identification of functional, verifiable, and therapeutic SSOs. We trained XGboost tree models using splicing factor (SF) pre-mRNA binding profiles and spliceosome assembly information to identify modulatory SSO binding sites on pre-mRNA. Using Shapley and out-of-bag analyses we also predicted the identity of specific SFs whose binding to pre-mRNA is blocked by SSOs. This step adds considerable transparency to AI/ML-driven drug discovery and informs biological insights useful in further validation steps. We applied this approach to previously established functional SSOs to retrospectively identify the SFs likely to regulate those events. We then took a prospective validation approach using a novel target in triple negative breast cancer (TNBC), NEDD4L exon 13 (NEDD4Le13). Targeting NEDD4Le13 with an AI/ML-designed SSO decreased the proliferative and migratory behavior of TNBC cells via downregulation of the TGFβ pathway. Overall, this study illustrates the ability of AI/ML to extract actionable insights from RNA-seq data. Synopsis: Machine learning models are trained to identify functional splice-switching oligonucleotides (SSOs) and to predict the splicing factors (SFs) inhibited. SSOs are developed for a novel target in Triple Negative Breast Cancer. Three sources of splicing regulatory information are used to train interpretable XGboost models that predict binding sites for functional SSOs and allow for the identification of SFs regulated by an SSO. The model shows high predictive accuracy in SF-binding perturbation positions critical for AS regulation. A novel alternative splicing target is identified in TNBC, NEDD4L exon 13 (NEDD4Le13). Targeting NEDD4Le13 with the SSO predicted by the model decreases TNBC cell proliferation and migration via downregulation of the TGFβ pathway. Machine learning models are trained to identify functional splice-switching oligonucleotides (SSOs) and to predict the splicing factors (SFs) inhibited. SSOs are developed for a novel target in Triple Negative Breast Cancer. [ABSTRACT FROM AUTHOR]

Background: EU Commission Regulation 2017/1410 prohibits using atranol and chloroatranol, the main allergens in Evernia prunastri (oakmoss), and hydroxyisohexyl 3‐cyclohexene carboxaldehyde (HICC) in cosmetic products. Oakmoss absolute is contained in fragrance mix (FM) I and HICC in FM II which are patch tested as screening mixtures in the baseline series. Objective: To describe the time trends of reaction frequencies to both FMs as well as to their components in FM‐positive patients. Methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2012–2021. Results: Positive reactions to FM I (FM II) declined from 9.1% (4.7%) in 2012 to 4.6% (3.0%) in 2021. Full breakdown tests were performed in 24% (FM I) and 31% (FM II), respectively, of the mix‐positive patients. From this data, frequencies of sensitization to the 14 single fragrances of FM I and FM II were calculated. For the majority, a decline was noted from 2012/2013 to 2020/2021, for oakmoss absolute 1.9%–0.8% and for HICC 1.8%–0.9%. Conclusion: EU Commission Regulation 2017/1410 was an effective measure. However, our data have some limitations, possibly causing underestimation of sensitization frequencies to fragrances. [ABSTRACT FROM AUTHOR]

Background: From 2006 to 2014, alcohol‐related visits to the emergency department (ED) increased by 76% in the United States, highlighting the need for improved ED‐driven interventions addressing alcohol use disorder (AUD). Naltrexone is an FDA‐approved medication for AUD shown to decrease craving and self‐administration of alcohol. While oral naltrexone and extended‐release naltrexone have been long utilized in primary care and inpatient hospital settings, the use of naltrexone in the ED is limited. Methods: This study implemented and analyzed a multifaceted intervention regarding ED naltrexone prescribing at a large safety net, academic, urban hospital. A baseline assessment of preintervention conditions and perspectives on naltrexone prescribing was conducted through a chart review and standardized interviews with ED providers, respectively. The interview results guided design of interventions that addressed identified barriers. These included provider education, prescribing aids, and zero‐cost naltrexone tablets supplied by the ED pharmacy to patients upon discharge. Results: Between September 1, 2019, and August 31, 2020, of 753 unique patients who had a primary diagnosis or chief complaint containing the word "alcohol," only five (0.66%) were prescribed naltrexone. ED providers identified lack of training regarding naltrexone, lack of a prescribing protocol, and limited patient and provider education materials as barriers to prescribing naltrexone. Following the intervention, among 278 eligible patients, 11 oral naltrexone prescriptions were written (3.96%) between April 13, 2021, and August 1, 2021. This represents a sixfold increase over the preintervention period. Conclusions: An intervention to increase ED oral naltrexone prescriptions for AUD was successfully implemented, addressing lack of provider education, lack of prescribing resources, and patient barriers to accessing prescribed medications. Longer‐term follow‐up is needed to assess the efficacy and sustainability of these interventions. Nevertheless, ED clinicians are well positioned to initiate naltrexone prescriptions for patients presenting with AUD. [ABSTRACT FROM AUTHOR]

Changes in the pharmacokinetic and resulting pharmacodynamic properties of drugs are common in many chronic liver diseases, leading to adverse effects, drug interactions and increased risk of over‐ or underdosing of medications. Structural and functional hepatic impairment can have major effects on drug metabolism and transport. This review summarizes research on the functional changes in phase I and II metabolic enzymes and in transport proteins in patients with metabolic diseases such as type 2 diabetes, metabolic dysfunction‐associated steatotic liver disease, metabolic dysfunction‐associated steatohepatitis and cirrhosis, providing a clinical perspective on how these changes affect drug uptake and metabolism. Generally, a decrease in expression and/or activity of many enzymes of the cytochrome P450 family (e.g. CYP2E1 and CYP3A4), and of influx and efflux transporters (e.g. organic anion‐transporting polypeptide [OATP]1B1, OATP2B1, OAT2 and bile salt export pump), has been recently documented in patients with liver disease. Decreased enzyme levels often correlate with increased severity of chronic liver disease. In subjects with hepatic impairment, there is potential for strong alterations of drug pharmacokinetics due to reduced absorption, increased volume of distribution, metabolism and extraction. Due to the altered pharmacokinetics, specific drug–drug interactions are also a potential issue to consider in patients with liver disease. Given the huge burden of liver disease in western societies, there is a need to improve awareness among all healthcare professionals and patients with liver disease to ensure appropriate drug prescriptions. [ABSTRACT FROM AUTHOR]

Introduction: In San Francisco, there were 638 accidental overdose deaths involving opioids in 2022 alone, with opioid overdoses occurring at a disproportionate rate in the Black population and in those with fixed housing. Past studies attempting to address such disparities suggest that low‐barrier buprenorphine (BUP) treatment models may improve patient engagement and retention in care for marginalized populations. While such models have been studied among persons experiencing houselessness (PEH), less is known about the effects of such treatment models among individuals residing in permanent supportive housing (PSH). Objectives: To evaluate the impact of an innovative pharmacist‐led pilot service in providing more equitable and accessible BUP treatment to individuals residing in PSH. Methods: This was a 3‐month pre‐and‐post interventional pilot study to evaluate the impact of a novel pharmacist‐led outreach service on patient engagement in treatment with BUP for Opioid Use Disorder (OUD). The primary endpoint was treatment adherence, defined as 80% prescription days covered (PDC) in a 3‐month period. Secondary endpoints included change in PDC, linkage to office‐based care, incidence of overdose, emergency department (ED) presentations, and hospital admissions, as well as successful BUP initiation. Results: Thirty‐eight patients were enrolled in the pharmacist‐led BUP outreach service. Among the 38 patients, the mean age was 46 years and 16 (42%) were Black. Engagement with the service was associated with increased treatment adherence, with 14 patients (37%) achieving ≥80% PDC post‐intervention compared to 1 patient (3%) pre‐intervention (p = 0.0009). Conclusion: A pharmacist‐led BUP outreach service was found to increase treatment adherence in individuals residing in PSH over 3 months. Low‐barrier BUP treatment models, such as that evaluated in this study, may help provide more equitable and accessible care that is critical in addressing the socioeconomic and racial disparities in opioid overdose deaths. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine whether children with healthy weight who vary by familial risk for obesity differ in executive functioning. Methods: Children (age 7–8 years) without obesity (n = 93, 52% male) who differed by familial risk for obesity (based on maternal weight status) completed go/no‐go and stop‐signal tasks to assess inhibitory control and an N‐back task to assess working memory. Dual energy x‐ray absorptiometry measured adiposity. Linear and mixed‐effect models assessed unique effects and relative importance analysis‐quantified relative effects of familial risk and percent body fat. Results: Children at high compared with low familial risk showed worse inhibitory control; however, child adiposity was not associated with inhibitory control. Both high familial risk and greater child adiposity were associated with worse N‐back performance when cognitive demand was high (2‐back), but not low (0‐ and 1‐back). The relative effect of familial risk on executive functioning was 2.7 to 16 times greater than the relative effect of percent body fat. Conclusions: These findings provide initial evidence that deficits in executive functioning may precede the development of obesity in children at high familial risk for this disease. Additional family risk studies are needed to elucidate the pathways through which maternal obesity influences child executive functioning and risk for obesity. [ABSTRACT FROM AUTHOR]

Background and Aims: The presence of significant liver fibrosis associated with non‐alcoholic steatohepatitis (NASH) is regarded as the major prognostic factor in non‐alcoholic fatty liver disease (NAFLD). Identification of patients at risk for NASH with significant fibrosis is therefore important. Although the established fibrosis score FIB‐4 is suitable to exclude advanced fibrosis, it does not allow the prediction of significant fibrosis in NAFLD patients. We therefore evaluated whether the hepatokine fibroblast growth factor 21 (FGF21), a regulator of glucose and lipid metabolism, might identify 'at‐risk NASH' in NAFLD. Methods: FGF21 levels were assessed by enzyme‐linked immunosorbent assay in sera from an exploration (n = 137) and a validation (n = 88) cohort of biopsy‐proven NAFLD patients with different disease activity and fibrosis stages. In addition, we evaluated whether the use of FGF21 could improve risk stratification in NAFLD patients with low (<1.3) or intermediate (1.3–2.67) FIB‐4. Results: FGF21 levels could significantly discriminate between NASH and non‐alcoholic fatty liver (NAFL) patients, even in the absence of diabetes. Moreover, patients with NASH and fibrosis ≥F2 showed significantly higher FGF21 levels compared to NAFLD patients without significant fibrosis. Significantly elevated FGF21 levels could even be detected in NAFLD patients with NASH and significant fibrosis despite low or intermediate FIB‐4. Conclusion: Serological FGF21 detection might allow the identification of NAFLD patients at risk and improves patient stratification in combination with FIB‐4. [ABSTRACT FROM AUTHOR]

Background and Aims: Data on number of patients with cirrhosis in Germany are limited. We therefore aimed to estimate prevalence, comorbidities, mortality, utilization of healthcare resources and costs of patients with cirrhosis and incidence of decompensation of cirrhosis in Germany. Methods: This longitudinal observational study was based on an anonymized representative claims database including 4.9 million persons insured by a statutory health insurance (SHI) between 2015–2020. Patients with decompensated and compensated cirrhosis were selected via diagnostic ICD codes and followed for 2 years. Results: Prevalence of cirrhosis in 2015 was 250/100 000, resulting in 201 747 (95% CI: 197 540–206 040) patients extrapolated to the German population. Out of all patients with compensated cirrhosis in 2015 who did not deceased, 16.0% developed a decompensation within 3 years. Overall, 978 patients (Ø‐age: 68 years; 60% male) were included in the decompensated, and 5135 patients (Ø‐age: 66 years; 59% male) in the compensated cirrhosis cohort. Patients with decompensated cirrhosis had a higher burden of comorbidities (Charlson Comorbidity Index 7.3 vs. 4.4) and 3 times higher costs per quarter (7172 € vs. 2213 €) than patients with compensated cirrhosis. 1‐year mortality after decompensation was 51% compared to 8% in compensated cirrhosis. Of note, only few patients with decompensated cirrhosis received a liver transplantation or transjugular intrahepatic portosystemic shunts (TIPS) (1% and 5%). Conclusion: Patients with cirrhosis have a high healthcare burden in especially decompensated stage. Accordingly, 1‐year mortality of decompensated cirrhosis in Germany is high. Despite high health resource utilization, only few patients have access to liver transplantation or TIPS. [ABSTRACT FROM AUTHOR]

Early‐onset Alzheimer's disease (AD) is highly heritable, yet only 10% of cases are associated with known pathogenic mutations. For early‐onset AD patients without an identified autosomal dominant cause, we hypothesized that their early‐onset disease reflects further enrichment of the common risk‐conferring single nucleotide polymorphisms associated with late‐onset AD. We applied a previously validated polygenic hazard score for late‐onset AD to 193 consecutive patients diagnosed at our tertiary dementia referral center with symptomatic early‐onset AD. For comparison, we included 179 participants with late‐onset AD and 70 healthy controls. Polygenic hazard scores were similar in early‐ versus late‐onset AD. The polygenic hazard score was not associated with age‐of‐onset or disease biomarkers within early‐onset AD. Early‐onset AD does not represent an extreme enrichment of the common single nucleotide polymorphisms associated with late‐onset AD. Further exploration of novel genetic risk factors of this highly heritable disease is warranted. Highlights: There is a unique genetic architecture of early‐ versus late‐onset Alzheimer's disease (AD).Late‐onset AD polygenic risk is not an explanation for early‐onset AD.Polygenic risk of late‐onset AD does not predict early‐onset AD biology.Unique genetic architecture of early‐ versus late‐onset AD parallels AD heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Hair cosmetic products contain several, partly potent contact allergens, including excipients like preservatives. Hand dermatitis in hairdressers is common, scalp and face dermatitis in clients or self‐users (summarised here as 'consumers') may be severe. Objective: To compare frequencies of sensitization to hair cosmetic ingredients and other selected allergens between female patch tested patients working as hairdressers and consumers without professional background, respectively, who were tested for suspected allergic contact dermatitis to such products. Methods: Patch test and clinical data collected by the IVDK (https://www.ivdk.org) between 01/2013 and 12/2020 were descriptively analysed, focusing on age‐adjusted sensitization prevalences in the two subgroups. Results: Amongst the 920 hairdressers (median age: 28 years, 84% hand dermatitis) and 2321 consumers (median age: 49 years, 71.8% head/face dermatitis), sensitization to p‐phenylenediamine (age‐standardised prevalence: 19.7% and 31.6%, respectively) and toluene‐2,5‐diamine (20 and 30.8%) were most common. Contact allergy to other oxidative hair dye ingredients was also more commonly diagnosed in consumers, whereas ammonium persulphate (14.4% vs. 2.3%) and glyceryl thioglycolate (3.9 vs. 1.2%) as well as most notably methylisothiazolinone (10.5% vs. 3.1%) were more frequent allergens in hairdressers. Conclusions: Hair dyes were the most frequent sensitizers both in hairdressers and in consumers; however, as indication for patch testing may differ, prevalences cannot directly be compared. The importance of hair dye allergy is evident, often with marked coupled reactivity. Workplace and product safety need to be further improved. [ABSTRACT FROM AUTHOR]

Background: Hydroperoxides of limonene (Lim‐OOHs) and linalool (Lin‐OOHs) are potent contact sensitizers. Objectives: To investigate the prevalence of positive patch test (PT) reactions to Lim‐OOHs and Lin‐OOHs in consecutive patients, their demographic factors and concomitant reactions. Methods: Between 7/2018 and 12/2020, Lim‐OOHs 0.3% pet. and Lin‐OOHs 1% pet. were patch tested in 5511 consecutive patients. We assessed PT reactivity and analysed data from patients with either positive or negative PTs to Lim‐OOHs and Lin‐OOHs. Results: Positive PT results to Lim‐OOHs (n = 170, 3.1%) and Lin‐OOHs (n = 483, 8.8%) were frequent. Most of the positive reactions were weak (LimOOHs n = 134/LinOOHs n = 429), and even more frequently, doubtful (n = 252/n = 578) or irritant reactions (n = 81/n = 178) were documented. PT reactivity to Lim‐OOHs and Lin‐OOHs was increased in patients with irritant reactions to sodium lauryl sulphate (SLS). The proportion of leg dermatitis and concomitant positive reactions to fragrances and essential oils was increased in patients with reactivity to these hydroperoxides. Conclusion: The observed reaction pattern suggests that both test preparations display an irritant potential with an increased risk of false positive reactions. Preparations should be chemically monitored in order to reduce irritancy. Mindful interpretation of PT results and aimed patch testing of lower concentrations is recommended. [ABSTRACT FROM AUTHOR]

Background: Benzisothiazolinone (BIT; CAS no. 2634‐33‐5) is used as a biocide in various products, including water‐based paints, metalworking fluids, and household products. In recent years, increasing sensitization rates have been observed in Europe. Objective: To describe a time trend of sensitization to BIT, analyse concomitant reactions, and identify patients with increased risk of BIT sensitization. Methods: Retrospective analysis of data from 26 739 patients patch tested with BIT, sodium salt, 0.1% petrolatum as part of several special test series within the Information Network of Departments of Dermatology (IVDK), 2002 to 2021. Results: Positive reactions to BIT were noted in 771 patients (2.9%). Sensitization frequency varied over time and increased in recent years, peaking at 6.5% in 2020. Painters and metalworkers handling metalworking fluids, but not cleaners, had a significantly increased risk of BIT sensitization. From our data, there is no evidence of immunological cross‐reactivity between BIT and other isothiazolinones. Conclusion: The increasing frequency of sensitization justifies adding BIT to the baseline series. More research on the clinical relevance of positive patch test reactions to BIT and the cause for the rising numbers of BIT sensitization is needed. [ABSTRACT FROM AUTHOR]

Cleaning avoids cross‐contamination and sustains production safety and efficiency. While there have been discoveries for technical surfaces, data on activities for filter cloth are still in the early stages. In the food industry, there is a lack of knowledge and innovative ideas on how to clean cloths efficiently. This study combined high‐speed recordings with cleaning experiments. Cleaning of eleven filters was captured, enabling time‐resolved analysis of the cleaning degree, the cleaning homogeneity, and insights into the mechanisms. The findings divide cloth cleaning into three phases, each significantly influenced by the properties of the cloth. Exemplarily, close‐mesh cloths have smoother surfaces that facilitate cleaning. Coarse structures with flow channels on the cloth surface can complicate cleaning. [ABSTRACT FROM AUTHOR]

The role of patella height is discussed controversially in total knee arthroplasty (TKA). Therefore, this computational study aims to systematically analyze the biomechanical effect of different patella heights on patellofemoral (PF) forces and kinematics after cruciate‐retaining (CR) TKA. We implemented a CR bicondylar TKA with a dome patellar button in a validated dynamic musculoskeletal multibody model of a male human knee joint. Retropatellar dynamics (contact force [N], shear force [N], patellar shift [mm], tilt [°], and rotation [°]) were evaluated during dual‐limb squat motion (flexion from 0° to 90°) with simulated active muscle forces and the effects of different patella heights (Blackburne‐Peel [BP] ratio of 0.39, 0.49, 0.65, 0.85, 1.01, and 1.1 were systematically examined). As active knee flexion increased, PF contact force also increased. Patella alta (BP = 1.1) resulted in higher PF contact forces compared to normal patella height (BP = 0.65) by up to 16%. Contrarily, patella baja was associated with decreased PF forces by 7%. Compared to patella baja (BP = 0.39), patella alta (BP = 1.1) considerably increased the contact force by up to 25%. Different patellar heights mainly affected PF shear forces during early knee flexion. Concerning PF kinematics, patella alta (BP = 1.1) yielded a greater lateral tilt of more than 4° and higher patellar rotation by up to 3° during deep knee flexion, compared to normal patella height (BP = 0.65). Our computational study indicates that patella alta is associated with the highest PF contact and shear force after the implantation of a CR bicondylar TKA. This should be considered in PF disorders following TKA. [ABSTRACT FROM AUTHOR]

Background: Blood‐brain barrier (BBB) dysfunction is considered a hallmark of Alzheimer's disease (AD), making non‐invasive imaging of BBB with arterial spin labeling (ASL) MRI a potential imaging biomarker (BBB‐ASL). However, the normal BBB development over the lifespan is unknown. Here, we created population‐based BBB‐ASL permeability reference maps, and aimed to investigate associations between BBB‐ASL, chronological age, and biological cerebrovascular age – expressed as white matter hyperintensities (WMH) volume. Method: Cognitively‐unimpaired (CU) participants were included from Center for Lifespan Changes in Brain and Cognition (LCBC) (n = 28, age 58.9±16.1y) and University of Singapore (n = 30, age 55.8±6.1y). The Singapore cohort is known to be vascularly compromised and thus expected to have early cerebrovascular pathology in the form of WMH. Multi‐echo, multi‐post‐labeling‐delay pseudo‐continuous ASL images were acquired at two identical Siemens 3T scanners and analyzed with ExploreASL. Gray matter (GM) BBB water time‐of‐exchange (Tex) was quantified with and without partial‐volume correction (PVC). For Singapore data, WMH were segmented on 3D FLAIR. Linear regression models were used to investigate associations of Tex with age and WMH volume, with and without covarying for sex and site. Result: Both site population‐averages (Figure 1) show similar Tex patterns, with slightly higher posterior variability in the Singapore data. GM Tex was negatively associated with age (Figure 2A) irrespective of PVC, and after covarying for sex and site (Table 1). GM Tex was also negatively associated with WMH volume (β = ‐0.005, p = 0.012), although the association became non‐significant if both PVC and sex and site corrections were applied (β = ‐0.005, p = 0.068). Conclusion: Our findings support the hypothesis of increased BBB permeability with aging and there are signs of association with increased cerebrovascular age assessed with WMH volume. We aim to further increase our sample size and also investigate associations with other AD biomarkers. [ABSTRACT FROM AUTHOR]

Full‐length sequence of HLA‐DRB3*03:46 covers the 5′‐untranslated region (UTR), all introns and exons and the 3′ UTR. [ABSTRACT FROM AUTHOR]

Background: Few therapeutic options are approved as second‐line treatment after failure of platinum‐based chemotherapy for patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). Topotecan widespread use remains challenged by the risk of severe toxicities in a pretreated population. Little is known about the efficacy and safety of epirubicin–paclitaxel doublet in second‐line and beyond and especially cerebral outcomes. Methods: EpiTax is a retrospective multicenter observational real‐life study. We evaluated the efficacy of epirubicin 90 mg/m2 combined with paclitaxel 175 mg/m2 every 3 weeks in SCLC patients after failure of at least one line of platinum‐based chemotherapy. The primary endpoint was progression‐free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), intracranial control rate (ICR), and safety. Results: A total of 29 patients were included. The median of previous systemic therapy lines was 2 (1–4). Eleven patients received the treatment in the second line. Characteristics of patients were a median age of 60 years (45–77), 65.5% of males with 72.4% of PS 0–1. Fifteen patients had a history of brain metastases. Median PFS and OS achieved 11.0 (95% CI, 8.1–16.3) and 23 (95% CI, 14.1–29.6) weeks, respectively. ORR was 34.5% and DCR was 55.2%. ICR was 3/15 (20%). Grade 3–4 adverse events were mainly hematological and concerned 7 patients. No case of febrile neutropenia or toxic death was reported. Conclusion: Epirubicin–paclitaxel association highlighted promising efficacy with PFS and OS of 11 and 23 weeks, respectively, ORR of 34.5%, and a tolerable safety profile. This doublet could represent another valuable therapeutic option for ES‐SCLC patients treated in the second line and beyond. [ABSTRACT FROM AUTHOR]

Patch testing shellac in consecutive patients - Data of the Information Network of Departments of Dermatology (IVDK) 2021 Keywords: allergic contact dermatitis; cosmetics; epidemiology; patch test; shellac; tattoo EN allergic contact dermatitis cosmetics epidemiology patch test shellac tattoo 77 80 4 12/21/22 20230101 NES 230101 INTRODUCTION Shellac ("lac resin", "lacca", "gum lac", CAS: 9000-59-3) is purified by alcoholic extraction from a resin secreted by female I Laccifer lacca i (Coccidae).[1] Shellac is mainly produced in Thailand, China, Myanmar, and India and is used in a wide range of applications as a binder (e.g., in lacquers, tattoo inks), emollient (e.g., in lipstick), for hair fixing (hair spray), as a film forming agent in several types of coatings, for example, of food (E904) and oral medication, as well as thickener in cosmetics like mascara and eyeliner.[1] Terpenic acids are main constituents (~50%) of shellac without substantial variation between samples of different origin.[2] In the literature, allergic contact dermatitis to shellac was recently described from using hair spray,[3] a mouthguard,[4] tattoo ink[5] and in the occupational context of food handlers.[6] In two cross-sectional patch test (PT) studies of the North American Contact Dermatitis Group from 2009-2010 and 2011-2012, positive reactions to shellac were detected in 1.6% and 1.7% of the patients, respectively.[[7]] METHODS To investigate the diagnostic performance of the PT preparation (20% alc, Chemotechnique Diagnostics, Vellinge, Sweden) and to identify potential risk factors of sensitization, shellac was patch tested in a subset of 21 departments joining the IVDK (www.ivdk.org) in an extension of the German Contact Dermatitis Research Group (DKG) baseline series in 2021. Sixty-eight of 76 patients with positive PTs to shellac were tested with colophony, 56 with propolis, all 3 preparations in 53 patients. [Extracted from the article]

Background: Massage therapists are particularly exposed to constituents of massage preparations, wet work and mechanical strain and therefore, at high risk to develop occupational dermatitis (OD). Objectives: To describe the sensitization spectrum of massage therapists with OD. Patients and Methods: In a retrospective study, patch test data of patients with OD (128 massage therapists and 24 374 patients working in other professions) collected by the Network of Departments of Dermatology (IVDK, 2008–2020) were analysed. Results: Hand dermatitis (91.4%) and allergic contact dermatitis (34.4%) were common in massage therapists with OD. Most frequent were sensitizations to fragrances/essential oils which were found in 54 (42.2%) massage therapists and thus, more often than in other patients with OD. Concomitant positivity to several fragrances/essential oils was frequent. In 8 (14.8%) of the 54 massage therapists, sensitizations to fragrances/essential oils were not detected with the baseline series, but only with special fragrance series. Conclusions: Allergic contact dermatitis is common in massage therapists with OD and is mainly caused by fragrances and essential oils. Hence, massage therapists should be aware of this risk. When OD is suspected, not only the baseline series, but also special fragrance series should be patch tested in this occupational group. [ABSTRACT FROM AUTHOR]

HLA‐DPA1*01:144 differs from HLA‐DPA*01:03:01:04 by one nucleotide substitution at position 44, codon‐17 located in exon 1. [ABSTRACT FROM AUTHOR]

Keywords: CAS 39423-51-3; case report; metalworking fluid; occupational allergic contact dermatitis; patch testing; trimethylolpropane poly(oxypropylene)triamine EN CAS 39423-51-3 case report metalworking fluid occupational allergic contact dermatitis patch testing trimethylolpropane poly(oxypropylene)triamine 74 76 3 06/12/23 20230701 NES 230701 Trimethylolpropane poly(oxypropylene)triamine (TMPPOPT) (CAS 39423-51-3)[1] is a reaction product of propylidynetrimethanol, propylene oxide and ammonia. CAS 39423-51-3, case report, metalworking fluid, patch testing, trimethylolpropane poly(oxypropylene)triamine, occupational allergic contact dermatitis TMPPOPT showed no sensitizing properties in a Buehler test in guinea pigs.[2] To our knowledge, no cases of contact allergy to TMPPOPT in humans have been described so far. [Extracted from the article]

Background and aims: Patients with cirrhotic refractory ascites ineligible for transjugular intrahepatic shunt (TIPSS) have limited treatment options apart from repeated large volume paracentesis. The alfapump® is an implantable device mobilizing ascites from the peritoneal cavity to the bladder, from where it can be excreted. The aim of this observational cohort study was to prospectively investigate safety and efficacy of the device in a real‐world cohort with cirrhotic refractory ascites and contraindications for TIPSS. Methods: A total of 106 patients received an implant at 12 European centres and were followed up for up to 24 months. Complications, device deficiencies, frequency of paracentesis, clinical status and survival were recorded prospectively. Results: Approximately half of the patients died on‐study, about a quarter was withdrawn because of serious adverse events leading to explant, a sixth were withdrawn because of liver transplant or recovery, and nine completed follow‐up. The most frequent causes of on‐study death and complication‐related explant were progression of liver disease and infection. The device reduced the requirement for large‐volume paracentesis significantly, with more than half of patients not having required any post‐implant. Survival benefits were not observed. Device‐related reinterventions were predominantly caused by device deficiencies. A post‐hoc comparison of the first 50 versus the last 50 patients enrolled revealed a decreased reintervention rate in the latter, mainly related to peritoneal catheter modifications. Conclusions: The device reduced paracentesis frequency in a real‐world setting. Technical complications were successfully decreased by optimization of management and device modification (NCT01532427). [ABSTRACT FROM AUTHOR]

Tin and mixed tin/germanium thin films hold great potential for a variety of different applications such as anodes for lithium ion batteries or optical components in new LED developments. While the physical and chemical properties of these materials are promising, the fabrication of nanostructures with tunable composition and electronic properties is eminently important to overcome several problems in application. In this work we report on the preparation and characterization of inverse opal‐structured Sn and Sn/Ge thin films with a pore size of 200 nm on a wide variety of substrates obtained by a simple, up‐scalable wet‐chemical synthetic route involving soluble [Sn9]4−, [Ge9]4− and mixed Sn/Ge Zintl clusters. The resulting honeycomb structures are characterized by SEM, EDX, XPS, and Raman spectroscopy. Their porous structure and tuneable composition makes them attractive candidates for electrochemical applications such as anode materials. [ABSTRACT FROM AUTHOR]

Previous research suggest that gratitude interventions are effective in improving mental well‐being, which might be beneficial to university students during the COVID‐19 pandemic. This quasi‐experimental study sought to investigate if a gratitude intervention will lead to higher mental well‐being of university students during the COVID‐19 pandemic. Participants (N = 47) mental well‐being was assessed before and after 10 weekly gratitude reflection journals and statistically compared with a control group (N = 40). An analysis of covariance (ANCOVA) was used to analyze the data. The treatment group showed significantly higher well‐being after the gratitude intervention compared with the control group (Cohen's d = 0.74). The treatment group significantly increased (Cohen's d = 0.35) and the control group significantly decreased (Cohen's d = −0.41). Gratitude interventions may be effective in improving the mental well‐being of university students even during a crisis such as the COVID‐19 pandemic. Gratitude interventions seem suitable for improving mental well‐being for temporary mental challenges of university students such as a pandemic or other forms of crisis. [ABSTRACT FROM AUTHOR]

Background: Essential oils (EOs) are widely used in cosmetics, perfumes, massage fluids, aroma therapy and natural medicine. Some EOs contain contact sensitizers. Objectives: To describe the frequency of sensitization to EOs in dermatitis patients presenting in skin clinics including concomitant reactions, to evaluate the EO patch test preparations and to identify patient groups with an increased risk of EO sensitization. Patients and methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010–2019. Results: Twelve EOs were patch tested in an aimed manner in 10 930 patients, of whom 908 (8.3%) reacted to at least 1 EO. Only 6 EOs elicited more than 1% positive patch test reactions: ylang ylang (I + II) oil (3.9%), lemongrass oil (2.6%), jasmine absolute (1.8%), sandalwood oil (1.8%), clove oil (1.6%) and neroli oil (1.1%). Concomitant reactions among EOs or to EOs and fragrances were frequent. Among EO‐positive patients, women, leg dermatitis patients, patients aged 40 years or more, masseurs and cosmeticians were over‐represented. Conclusions: Sensitization to EOs occurs, albeit infrequently in most cases. Masseurs and cosmeticians have an increased risk of sensitization to EOs. [ABSTRACT FROM AUTHOR]

Summary: This paper presents a novel method to remove spent grains efficiently from filter cloths via pulsed forward flushes. In breweries, mash filters separate liquid wort from solid spent grains, a by‐product. These mash filters use woven fabrics made from synthetic materials as filter media. However, rough filter surfaces often hinder the cleaning process. Concerning modern hygienic design principles, filter cloths are only designed for efficient filtration performances, in which cleanability is not considered. Hence, in combination with strongly adhesive spent grains, brewers often reject mash filters. The paper illustrates an experimental parameter variation and a comparison of pulsed with continuous cleaning in respect to their cleaning performance. The results showed that the proposed method is suitable, reaching up to 30% higher cleaning degrees than conventional methods. Furthermore, the technique required up to 50% fewer cleaning fluids and shorter cleaning times, indicating economic and ecological advantages. [ABSTRACT FROM AUTHOR]

Keywords: 2,4,6-Tris(dimethylaminomethyl)phenol; CAS 90-72-2; epoxy resin; patch testing; tris-DMP EN 2,4,6-Tris(dimethylaminomethyl)phenol CAS 90-72-2 epoxy resin patch testing tris-DMP 316 318 3 03/15/23 20230401 NES 230401 2,4,6-Tris(dimethylaminomethyl)phenol (tris-DMP; CAS No. 90-72-2) is a hardener/accelerator frequently used in epoxy resin systems (ERS), especially at low ambient temperature.[1] First cases of contact sensitization to tris-DMP have been observed at the Finnish Institute of Occupational Health (FIOH) around 1990.[2] Since then, contact sensitization to tris-DMP has been described in several case reports from various European countries.[1] In the FIOH, 14 cases of contact sensitization to tris-DMP have been registered from 1991 to 2013, rendering it the second most frequent sensitizer among epoxy resin hardeners.[1] Since 2016, tris-DMP is available as patch test preparation at 0.5% in pet. from Chemotechnique, Vellinge, Sweden. However, 9 out of 14 FIOH patients (64%) sensitized to tris-DMP, but only 3 of the 28 tris-DMP positive IVDK patients (11%), were painters. DISCUSSION Consistent with the FIOH data,[1] we found sensitizations to tris-DMP less frequently than sensitizations to MXDA, but with a similar frequency as sensitizations to IPDA. [Extracted from the article]

Background: Benzyl alcohol is a widely used preservative, solvent and fragrance material. According to published data, it is a rare sensitizer in humans. Objectives: To identify characteristics and sensitization patterns of patients with positive patch test reactions to benzyl alcohol and to check the reliability of the patch test preparation benzyl alcohol 1% pet. Patients and Methods: Retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2010–2019. Results: Of 70 867 patients patch tested with benzyl alcohol 1% pet., 146 (0.21%) showed a positive reaction, most of them (89%) only weakly positive. The number of doubtful and irritant reactions significantly exceeded the number of positive reactions. Reproducibility of positive test reactions was low. Among benzyl alcohol‐positive patients, compared to benzyl alcohol‐negative patients, there were significantly more patients with leg dermatitis (17.8% vs. 8.6%), more patients aged 40 years or more (81.5% vs. 70.5%) and more patients who were tested because of a suspected intolerance reaction to topical medications (34.9% vs. 16.6%). Concomitant positive reactions were mainly seen to fragrances, preservatives and ointment bases. Conclusions: Sensitization to benzyl alcohol occurs very rarely, mainly in patients with stasis dermatitis. In view of our results, benzyl alcohol cannot be regarded as a significant contact allergen, and therefore marking it as skin sensitizer 1B and labelling it with H 317 is not helpful. [ABSTRACT FROM AUTHOR]

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Summary: Contact dermatitis is an inflammation of the epidermis and dermis at the site of exposure triggered by external agents. The two main forms are irritant and allergic contact dermatitis, which cause significant health and socioeconomic costs in addition to a marked reduction in quality of life. The anamnesis and the clinical picture are decisive for the necessary diagnostic measures. The most accurate possible diagnostic classification of contact dermatitis by means of allergological testing is important for disease management, since not only classical eczema therapy but also avoidance of the exogenous triggering factors are of great importance here. The choice of therapy should be based on the acuity, clinical severity, morphology of the lesions and localization of the contact dermatitis. A combination of basic therapy, topical, physical, and systemic therapy adapted to the patient's needs is required, whereby not all forms of therapy must be carried out simultaneously but can be used in a varying manner. Primary, secondary, and tertiary prevention strategies aim at the recognition of the triggering noxae or allergens with subsequent contact avoidance or minimization. The present S1‐guideline on contact dermatitis is primarily intended to provide dermatologists, allergologists and physicians working in allergology and occupational dermatology with a decision‐making aid for the selection and implementation of suitable and sufficient diagnostics, therapy, and prevention. [ABSTRACT FROM AUTHOR]

Background: Patch test (PT) readings are recommended after 48 h and 72 h (D3). An additional day 7 (D7) reading has been suggested by some, although data on efficient patient selection are scarce. We investigated positive D7 reactions regarding (i) allergens in the baseline series and additional PT series of the German Contact Dermatitis Research Group (DKG) and (ii) characteristics of the patients tested. Methods: Retrospective, multicentre analysis of 190 allergens derived from 17 DKG test series in 4687 patients with an additional D7 reading. Patients were patch tested with the baseline series and additional series, if required. Occurrence of novel D7 reactions as well as increasing skin reactions from D3 to D7 was analysed separately. Results: Depending on the allergen tested, waiving D7 readings would have missed 4.4–26.8% of positive PT results. Patch test series with the highest number of novel D7 reactions were baseline series, metal series, and leather/shoe series. New positive reactions on D7 were associated with age over 50 years and with a negative irritant control containing sodium lauryl sulphate. Of note, application of the PT allergens for 48 h instead of 24 h was positively associated with late PT reactions. Conclusion: Within the most frequently tested allergens, without late readings, on average 11.7% of sensitizations would have been missed. Novel late reacting allergens were identified. This study comprehensively dissects patient‐, allergen‐ and test‐dependent parameters in support for D7 readings. We propose to always consider late readings individually based on effort‐benefit considerations. [ABSTRACT FROM AUTHOR]

Full‐length sequence covers the 5′‐untranslated region (UTR), all introns and exons and the 3′ UTR. [ABSTRACT FROM AUTHOR]

Objective: At high altitude (HA), acute mountain sickness (AMS) is accompanied by neurologic and upper gastrointestinal symptoms (UGS). The primary aim of this study was to test the hypothesis that delayed gastric emptying (GE), assessed by 13C‐octanoate breath testing (OBT), causes UGS in AMS. The secondary aim was to assess post‐gastric mechanisms of OBT, which could confound results under these conditions, by determination of intermediary metabolites, gastrointestinal peptides, and basal metabolic rate. Methods: A prospective trial was performed in 25 healthy participants (15 male) at 4559 m (HA) and at 490 m (Zurich). GE was assessed by OBT (428 kcal solid meal) and UGS by visual analogue scales (VAS). Blood sampling of metabolites (glucose, free fatty acids (FFA), triglycerides (TG), beta‐hydroxyl butyrate (BHB), L‐lactate) and gastrointestinal peptides (insulin, amylin, PYY, etc.) was performed as well as blood gas analysis and spirometry. Statistical analysis: variance analyses, bivariate correlation, and multilinear regression analysis. Results: After 24 h under hypoxic conditions at HA, participants developed AMS (p < 0.001). 13CO2 exhalation kinetics increased (p < 0.05) resulting in reduced estimates of gastric half‐emptying times (p < 0.01). However, median resting respiratory quotients and plasma profiles of TG indicated that augmented beta‐oxidation was the main predictor of accelerated 13CO2‐generation under these conditions. Conclusion: Quantification of 13C‐octanoate oxidation by a breath test is sensitive to variation in metabolic (liver) function under hypoxic conditions. 13C‐breath testing using short‐chain fatty acids is not reliable for measurement of gastric function at HA and should be considered critically in other severe hypoxic conditions, like sepsis or chronic lung disease. [ABSTRACT FROM AUTHOR]

The accuracy and precision of soft sensors depend strongly on the reliability of underlying model inputs. These inputs (particularly readings of hardware sensors) are frequently subject to faults. This study aims to develop an adaptive soft sensor capable of reliable and robust biomass concentration predictions in the presence of faulty model inputs for a Pichia pastoris bioprocess. Hence, three soft sensor submodels were developed based on three independent model inputs (base addition, CO2 production, and mid‐infrared spectrum). An ensemble‐based algorithm combined the submodels to form an ensemble model, that is, an adaptive soft sensor, to achieve fault‐tolerant prediction. The algorithm's basic steps are as follows: the initial determination of submodel reliability is followed by selecting appropriate submodels to generate a reliable prediction via variance‐based weighting of the submodels. The adaptive soft sensor demonstrated high robustness and accuracy in biomass prediction in the presence of multiple simulated sensor faults (RMSE = 0.43 g L−1) and multiple real sensor faults (RMSE = 0.70 g L−1). [ABSTRACT FROM AUTHOR]

Of 131 patch-test positive patients, 24 (18.3%) reacted to both preparations, 98 (74.8%) to FMI only, and 9 (6.9%) to OM and not to FMI, although OM is a constituent of FMI. Keywords: allergic contact dermatitis; delayed reactions; fragrance; fragrance mix I; late reactions; oak moss absolute; patch test; patch test active sensitization EN allergic contact dermatitis delayed reactions fragrance fragrance mix I late reactions oak moss absolute patch test patch test active sensitization 54 57 4 12/17/21 20220101 NES 220101 Patch test reactions that become positive de novo at around day 7 (D7) are called "late" patch test reactions,1 and are frequently seen after patch testing neomycin, for example.2 Reactions beyond D7 ("very late reactions") may indicate active sensitization.1,3 However, very late reactions (2 to 4 weeks after patch testing) without being linked to active sensitization have also been observed.4-6 We were interested in very late reactions (beyond D7) in patch testing fragrance mix I (FMI) and oak moss absolute (OM). Regarding all positive reactions, 11/136 (8.1%) of FMI-positive patients and 11/45 (24.4%) of OM-positive patients showed very late reactions (Table 1). 1 TABLEResults of reading fragrance mix I (FMI) and oak moss absolute (OM) in n = 1789 patients at different points of time HT