Endoplasmic reticulum morphology regulation by RTN4 modulates neuronal regeneration by curbing luminal transport.

Cell functions rely on intracellular transport systems distributing bioactive molecules with high spatiotemporal accuracy. The endoplasmic reticulum (ER) tubular network constitutes a system for delivering luminal solutes, including Ca2+, across the cell periphery. How the ER structure enables this nanofluidic transport system is unclear. Here, we show that ER membrane-localized reticulon 4 (RTN4/Nogo) is sufficient to impose neurite outgrowth inhibition in human cortical neurons while acting as an ER morphoregulator. Improving ER transport visualization methodologies combined with optogenetic Ca2+ dynamics imaging and in silico modeling, we observed that ER luminal transport is modulated by ER tubule narrowing and dilation, proportional to the amount of RTN4. Excess RTN4 limited ER luminal transport and Ca2+ release, while RTN4 elimination reversed the effects. The described morphoregulatory effect of RTN4 defines the capacity of the ER for peripheral Ca2+ delivery for physiological releases and thus may constitute a mechanism for controlling the (re)generation of neurites.

In vitro T cell responses to PD-1 blockade are reduced by IFN-α but do not predict therapy response in melanoma patients.

PD-1 blockade therapy has revolutionized melanoma treatment, but still not all patients benefit and pre-treatment identification of those patients is difficult. Increased expression of inflammatory markers such as interleukin (IL)-6 in blood of patients correlates with poor treatment response. We set out to study the effect of inflammatory cytokines on PD-1 blockade in vitro. For this, we studied the effect of IL-6 and type I interferon (IFN) in vitro on human T cells in a mixed leukocyte reaction (MLR) in the absence or presence of PD-1 blockade. While IL-6 reduced IFN-γ secretion by T cells in both the presence and absence of PD-1 blockade, IFN-α specifically reduced the IFN-γ secretion only in the presence of PD-1 blockade. IFN-α reduced T cell proliferation independent of PD-1 blockade and reduced the percentage of cells producing IFN-γ only in the presence of PD-1 blockade. Next we determined the type I IFN score in a cohort of 22 melanoma patients treated with nivolumab. In this cohort, we did not find a correlation between clinical response and type I IFN score, nor between clinical response and IFN-γ secretion in vitro in a MLR in the presence of PD-1 blockade. We conclude that IFN-α reduces the effectiveness of PD-1 blockade in vitro, but that in this cohort, type I IFN score in vivo, nor IFN-γ secretion in vitro in a MLR in the presence of PD-1 blockade correlated to decreased therapy responses in patients.

Undifferentiated round cell sarcoma with CRTC1::SS18 fusion: Expanding clinicopathologic features of a rare translocation sarcoma with prominent desmoplastic stroma.

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS-non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, three cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report three additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range: 12 to 42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round to epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor (DSRCT). Immunohistochemical results were non-specific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exon 1-2 of CRTC1 (the 5' partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3' partner gene) on chromosome 18. The clinical course was variable. While one previously reported case demonstrated aggressive behavior with fatal outcome, two others had a relatively indolent course with gradual growth for 6-7 years prior to resection. Two cases developed metastatic disease, including one case with bilateral lung metastasis and one with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aim to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.

Financial burden and physical and emotional quality of life in COPD, heart failure, and kidney failure.

Patients with chronic and serious illnesses experience significant quality of life concerns. More research is needed to understand the impact of financial burden on patients with COPD, heart failure, and kidney failure. Patients with COPD, heart failure, or kidney failure completed a cross-sectional online survey using validated measures of financial burden (general financial strain as well as financial toxicity attributable to treatment), physical quality of life (symptom burden and perceived health), and emotional quality of life (anxiety, depression, and suicidal ideation). ANCOVA was used to examine whether financial strain and financial toxicity were associated with physical and emotional quality of life, while accounting for key covariates. Among 225 participants with COPD (n = 137), heart failure (n = 48), or kidney failure (n = 40), 62.2% reported general financial strain, with 34.7% experiencing financial toxicity attributable to treatments. Additionally, 68.9% rated their health as fair or poor, experiencing significant symptom burden including fatigue, dyspnea, and chest pain. Participants also reported clinically relevant levels of anxiety (55.1%), depression (52.0%), and suicidal ideation (21.8%). In the total sample, financial strain was associated with worse physical and emotional quality of life on all measures (all Ps < .001). Financial toxicity attributable to treatment was not associated with quality of life in the total sample or subsamples. Patients with COPD, heart failure, and kidney failure face significant financial, physical, and emotional burdens. Financial strain appears to undermine physical and emotional quality of life. Our study highlights the demand for interventions aimed at mitigating financial strain and toxicity experienced by individuals with chronic illnesses.

Synthesis and evaluation of 3,4,5-trisubstituted triazoles as G protein-biased kappa opioid receptor agonists.

Kappa opioid receptor (KOR) agonists represent promising therapeutics for pain relief due to their analgesic properties along with lower abuse potential than opioids that act at the mu opioid receptor. However, typical KOR agonists produce sedation and dysphoria. Previous studies have shown that G protein signaling-biased KOR agonists may present a means to untangle the desired analgesic properties from undesired side effects. In this paper, we report a new series of G protein signaling-biased KOR agonists entailing -S- → -CH2- replacement in a previously reported KOR agonist, triazole 1.1. With an optimized carbon linker in hand, further development of the scaffold was undertaken to investigate the appendages of the triazole core. The structure-activity relationship study of this series is described, including several analogues that display enhanced potency while maintaining G protein-signaling bias compared to triazole 1.1.

Cross-setting Comparison of Risk Factors for Pressure Injuries Acquired in Post-Acute Care.

GENERAL PURPOSE: To provide information on the association between risk factors and the development of new or worsened stage 2 to 4 pressure injuries (PIs) in patients in long-term care hospitals (LTCHs), inpatient rehabilitation facilities (IRFs), and skilled nursing facilities (SNFs). TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Compare the unadjusted PI incidence in SNF, IRF, and LTCH populations.2. Explain the extent to which the clinical risk factors of functional limitation (bed mobility), bowel incontinence, diabetes/peripheral vascular disease/peripheral arterial disease, and low body mass index are associated with new or worsened stage 2 to 4 PIs across the SNF, IRF, and LTCH populations.3. Compare the incidence of new or worsened stage 2 to 4 PI development in SNF, IRF, and LTCH populations associated with high body mass index, urinary incontinence, dual urinary and bowel incontinence, and advanced age.

A mixed methods evaluation of patient perspectives on the implementation of an electronic health record-integrated patient-reported symptom and needs monitoring program in cancer care.

BACKGROUND: As cancer centers have increased focus on patient-centered, evidenced-based care, implementing efficient programs that facilitate effective patient-clinician communication remains critical. We implemented an electronic health record-integrated patient-reported symptom and needs monitoring program ('cPRO' for cancer patient-reported outcomes). To aid evaluation of cPRO implementation, we asked patients receiving care in one of three geographical regions of an academic healthcare system about their experiences. METHODS: Using a sequential mixed-methods approach, we collected feedback in two waves. Wave 1 included virtual focus groups and interviews with patients who had completed cPRO. In Wave 2, we administered a structured survey to systematically examine Wave 1 themes. All participants had a diagnosed malignancy and received at least 2 invitations to complete cPRO. We used rapid and traditional qualitative methods to analyze Wave 1 data and focused on identifying facilitators and barriers to cPRO implementation. Wave 2 data were analyzed descriptively. RESULTS: Participants (n = 180) were on average 62.9 years old; were majority female, White, non-Hispanic, and married; and represented various cancer types and phases of treatment. Wave 1 participants (n = 37) identified facilitators, including cPRO's perceived value and favorable usability, and barriers, including confusion about cPRO's purpose and various considerations for responding. High levels of clinician engagement with, and patient education on, cPRO were described as facilitators while low levels were described as barriers. Wave 2 (n = 143) data demonstrated high endorsement rates of cPRO's usability on domains such as navigability (91.6%), comprehensibility (98.7%), and relevance (82.4%). Wave 2 data also indicated low rates of understanding cPRO's purpose (56.7%), education from care teams about cPRO (22.5%), and discussing results of cPRO with care teams (16.3%). CONCLUSIONS: While patients reported high value and ease of use when completing cPRO, they also reported areas of confusion, emphasizing the importance of patient education on the purpose and use of cPRO and clinician engagement to sustain participation. These results guided successful implementation changes and will inform future improvements.

Dominant suppressor genes of p53-induced apoptosis in Drosophila melanogaster.

One of a major function of programmed cell death (apoptosis) is the removal of cells which suffered oncogenic mutations, thereby preventing cancerous transformation. By making use of a Double-Headed-EP (DEP) transposon, a P element derivative made in our laboratory, we made an insertional mutagenesis screen in Drosophila melanogaster to identify genes which, when overexpressed, suppress the p53-activated apoptosis. The DEP element has Gal4-activatable, outward-directed UAS-promoters at both ends which can be deleted separately in vivo. In the DEP insertion mutants, we used the GMR-Gal4 driver to induce transcription from both UAS-promoters and tested the suppression effect on the apoptotic rough eye phenotype generated by an activated UAS-p53 transgene. By DEP insertions, seven genes were identified which suppressed the p53-induced apoptosis. In four mutants, the suppression effect resulted from single genes activated by one UAS-promoter (Pka-R2, Rga, crol, Spt5). In the other three (Orct2, Polr2M, stg), deleting either UAS-promoter eliminated the suppression effect. In qPCR experiments we found that the genes in the vicinity of the DEP insertion also showed an elevated expression level. This suggested an additive effect of the nearby genes on suppressing apoptosis. In the eucaryotic genomes there are co-expressed gene clusters. Three of the DEP insertion mutants are included and two are in close vicinity of separate co-expressed gene clusters. This raises the possibility that the activity of some of the genes in these clusters may help the suppression of the apoptotic cell death.

Heart failure events in randomized controlled trials for adults receiving maintenance dialysis: a meta-epidemiologic study.

BACKGROUND AND HYPOTHESIS: Heart failure is characterized as cardiac dysfunction resulting in elevated cardiac filling pressures with symptoms and signs of congestion. Distinguishing heart failure from other causes of similar presentations in patients with kidney failure is challenging but necessary, and is needed in randomized controlled trials (RCTs) to accurately estimate treatment effects. The objective of this study was to review heart failure events, their diagnostic criteria and adjudication in RCTs of patients with kidney failure treated with dialysis. We hypothesized that heart failure events, diagnostic criteria and adjudication were infrequently reported in RCTs in dialysis. METHODS: We conducted a meta-epidemiologic systematic review of RCTs from high impact medical, nephrology and cardiology journals from 2000 to 2020. RCTs were eligible if they enrolled adults receiving maintenance dialysis for kidney failure and evaluated any intervention. Results. Of 561 RCTs in patients receiving dialysis, 36 (6.4%) reported heart failure events as primary (10, 27.8%) or secondary (31, 86.1%) outcomes. 10 of the 36 (27.8%) RCTs provided heart failure event diagnostic criteria and 5 of these 10 (50%) adjudicated heart failure events. These 10 RCTs included event diagnostic criteria for heart failure or heart failure hospitalizations, and their criteria included dyspnea (5/10), edema (2/10), rales/crackles (4/10), chest x-ray pulmonary edema or vascular redistribution (4/10), treatment in an acute setting (6/10) and ultrafiltration or dialysis (4/10). No study explicitly distinguished heart failure from volume overload secondary to non-adherence or underdialysis. CONCLUSION: Overall, we found that heart failure events are infrequently reported in RCTs in dialysis and are heterogeneously defined. Further research is required to develop standardized diagnostic criteria that are practical and meaningful to patients and clinicians.

What Next for Eating Disorder Genetics? Replacing Myths With Facts to Sharpen Our Understanding.

Substantial progress has been made in the understanding of anorexia nervosa (AN) and eating disorder (ED) genetics through the efforts of large-scale collaborative consortia, yielding the first genome-wide significant loci, AN-associated genes, and insights into metabo-psychiatric underpinnings of the disorders. However, the translatability, generalizability, and reach of these insights are hampered by an overly narrow focus in our research. In particular, stereotypes, myths, assumptions and misconceptions have resulted in incomplete or incorrect understandings of ED presentations and trajectories, and exclusion of certain patient groups from our studies. In this review, we aim to counteract these historical imbalances. Taking as our starting point the Academy for Eating Disorders (AED) Truth #5 "Eating disorders affect people of all genders, ages, races, ethnicities, body shapes and weights, sexual orientations, and socioeconomic statuses", we discuss what we do and do not know about the genetic underpinnings of EDs among people in each of these groups, and suggest strategies to design more inclusive studies. In the second half of our review, we outline broad strategic goals whereby ED researchers can expand the diversity, insights, and clinical translatability of their studies. Appeared originally in Mol Psychiatry 2022; 27:3929-3938.

Skin and macular carotenoids and relations to academic achievement among school-aged children.

ABSTRACTObjectives: Carotenoids are plant pigments that accumulate in human tissue (e.g. macula and skin) and can serve as biomarkers for diet quality; however, knowledge on skin and macular carotenoids in relation to cognition in children is limited. This study aimed to address this gap by assessing links between skin and macular carotenoids and academic achievement in school-aged children.Methods: Children 7-12 years old (n = 81) participated in a crosssectional study. Skin and macular carotenoids were measured with reflection spectroscopy and heterochromatic flicker photometry, respectively. Academic achievement was measured using Woodcock-Johnson IV (WJ-IV). Body Mass Index was calculated using height and weight measurements, demographic information was collected using a family demographics and pediatric health history questionnaire, and carotenoid intake was assessed using 7-day diet records.Results: Skin carotenoids were not related to macular pigment (r = 0.08, p = 0.22). Adjusting for age, sex, BMI percentile, household income, and total carotenoid consumption (mg/1000kcal), skin carotenoids were predictive of math (ß = 0.27, p = 0.02), broad math (ß = 0.36, p < 0.01) and math calculation (ß = 0.38, p < 0.01). Skin carotenoids displayed trending relationships with broad reading (ß = 0.23, p = 0.05) and reading fluency (ß = 0.22, p = 0.07). There were no significant associations between macular pigment and academic achievement (all ß's ≤ 0.07, all p's ≥ 0.56).Discussion: Skin carotenoids were positively associated with academic abilities in children, while macular carotenoids did not display this relationship. Future interventions examining prospective effects of changes in carotenoids in different tissues on childhood academic achievement are warranted.

Sleep Disturbance Mediates the Associations Between HIV Stigma and Mental and Physical Health Among Black Adults with HIV.

OBJECTIVES: Black Americans have been disproportionally affected by the HIV epidemic, and experience significant disparities in sleep health, mental health, and physical health domains. Using longitudinal data from a sample of Black adults with HIV, the current study examined the associations between stigma and mental and physical health outcomes and how sleep disturbance may play a mediating role. METHODS: Data were drawn from a recent randomized controlled trial. Questionnaires were used to examine internalized and anticipated HIV stigma, perceived discrimination (enacted stigma) based on multiple social identities (i.e., HIV-serostatus, race, sexual orientation), sleep disturbance, mental health problems (depressive and posttraumatic stress disorder [PTSD] symptoms), and mental and physical health-related quality of life (HRQOL) at baseline, 7-month follow-up, and 13-month follow-up assessments. Linear mixed modeling was used to examine main effects of stigma on health outcomes; causal mediation analysis was used to estimate indirect paths through sleep disturbance. RESULTS: Internalized and anticipated HIV stigma and multiple discrimination were associated with more sleep disturbance, more depressive and PTSD symptoms, and poorer mental and physical HRQOL. Results also indicated significant indirect paths (i.e., mediation) through greater sleep disturbance between HIV-related stigma and discrimination and mental health and health-related quality of life. CONCLUSIONS: Results support that sleep disturbance is a mediating pathway through which different forms of stigmas impact health outcomes. Sleep may be an intervention target to help improve mental and physical well-being and reduce health disparities among racial and ethnic minority people with HIV.

Enhancing patient acceptance of ICD implantation through structured shared decision making: conversation is key.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-D) are lifesaving treatments for patients at risk for sudden cardiac death. Effective physician-patient communication during the shared decision-making process is essential. Electrophysiologist-patient conversations were targeted to obtain objective data on the interaction, understand the conversation framework, and uncover opportunities for improved communication. METHODS: Individuals previously identified as requiring an ICD/CRT-D but declined implantation were recruited for this four-stage interview and survey-based study. Quantitative analysis of surveys and AI analysis of conversation videos was conducted to evaluate patient participant expectations, analyze feedback about the conversations with study physicians, and gauge willingness for device implantation. RESULTS: The study included 27 patients (mean age 51 years, 51.9% female) and 9 study physicians. Patients were significantly more willing to undergo ICD/CRT-D implantation after conversing with study physicians compared to their own physicians and pre-conversation surveys (mean scores: 5.0, 3.1, and 4.4 out of 7, respectively; p < 0.001). Patient participants had higher satisfaction with the study conversation, rating study physicians higher in effectiveness of explanations, responsiveness to questions, and overall quality of the conversation compared to their own physicians (all p < 0.001). CONCLUSIONS: In a cohort of patients who previously declined ICD/CRT-D implantation, patient satisfaction and willingness to undergo implantation of a guideline-directed device therapy increased significantly following a structured conversation with study physicians. Identified key elements could be integrated into user-friendly tools and educational materials to facilitate these conversations, improving patient engagement with the decision-making process and enhancing informed acceptance of indicated device therapies.

Estimating ambient air pollutant concentrations outside and inside homes in the Subpopulations and Intermediate outcomes in COPD air pollution (SPIROMICS air) cohort.

BACKGROUND: Valid, high-resolution estimates of population-level exposure to air pollutants are necessary for accurate estimation of the association between air pollution and the occurrence or exacerbation of adverse health outcomes such as Chronic Obstructive Pulmonary Disease (COPD). OBJECTIVES: We produced fine-scale individual-level estimates of ambient concentrations of multiple air pollutants (fine particulate matter [PM2.5], NOX, NO2, and O3) at residences of participants in the Subpopulations and Intermediate Outcomes in COPD Air Pollution (SPIROMICS Air) study, located in seven regions in the US. For PM2.5, we additionally integrated modeled estimates of particulate infiltration based on home characteristics and measured total indoor concentrations to provide comprehensive estimates of exposure levels. METHODS: To estimate ambient concentrations, we used a hierarchical high-resolution spatiotemporal model that integrates hundreds of geographic covariates and pollutant measurements from regulatory and study-specific monitors, including ones located at participant residences. We modeled infiltration efficiency based on data on house characteristics, home heating and cooling practices, indoor smoke and combustion sources, meteorological factors, and paired indoor-outdoor pollutant measurements, among other indicators. RESULTS: Cross-validated prediction accuracy (R2) for models of ambient concentrations was above 0.80 for most regions and pollutants. Particulate matter infiltration efficiency varied by region, from 0.51 in Winston-Salem to 0.72 in Los Angeles, and ambient-source particles constituted a substantial fraction of total indoor PM2.5. CONCLUSION: Leveraging well-validated fine-scale approaches for estimating outdoor, ambient-source indoor, and total indoor pollutant concentrations, we can provide comprehensive estimates of short and long-term exposure levels for cohorts undergoing follow-up in multiple different regions.

The impacts of supplemental benefits on Medicare Advantage plan composition.

OBJECTIVES: In 2019 and 2020, Medicare Advantage (MA) plans received historic flexibility to begin to address members' nonmedical and social needs through a set of primarily health-related benefits (PHRBs) and Special Supplemental Benefits for the Chronically Ill (SSBCIs). We aimed to evaluate the impact of adoption on the number and composition of new MA plan enrollees. STUDY DESIGN: A difference-in-differences design of retrospective Medicare enrollment data linked to publicly available plan and county-level data. METHODS: We linked individual-level Medicare enrollment data to publicly available, plan-level MA benefit, crosswalk, and penetration files from 2016 to 2020. We compared the number of new enrollees and the proportion of new enrollees who were Black, Hispanic, younger than 65 years, partially and fully Medicare and Medicaid dual eligible, and disabled in plans that adopted a PHRB or SSBCI vs a set of matched control plans that did not. RESULTS: In fully adjusted models, PHRB adoption was associated with a 2.2% decrease in the proportion of fully dual-eligible new members (95% CI, -4.0% to -0.5%). SSBCI adoption was associated with a 2.3% decrease in the proportion of new members younger than 65 years (95% CI, -3.6% to -0.9%). After accounting for multiple comparisons, these results were no longer statistically significant. CONCLUSION: We determined that supplemental benefit adoption was not associated with demographic shifts in MA plan enrollment.

Non-clinical and clinical characterization of MAU868, a novel human-derived monoclonal neutralizing antibody targeting BK polyomavirus VP1.

Reactivation of BK polyomavirus (BKPyV) can cause significant kidney and bladder disease in immunocompromised patients. There are currently no effective, BKPyV-specific therapies. MAU868 is a novel, human IgG1 monoclonal antibody that binds the major capsid protein VP1 of BKPyV with picomolar affinity, neutralizes infection by the four major BKPyV genotypes (EC50 ranging from 0.009 to 0.093 µg/ml; EC90 ranging from 0.102 to 4.160 µg/ml), and has comparable activity against variants with highly prevalent VP1 polymorphisms. No resistance-associated variants were identified in long-term selection studies, indicating a high in vitro barrier-to-resistance. The high-resolution crystal structure of MAU868 in complex with VP1 pentamer identified three key contact residues in VP1 (Y169, R170, K172). A first-in-human study was conducted to assess the safety, tolerability, and pharmacokinetics of MAU868 following intravenous and subcutaneous administration to healthy adults in a randomized, placebo-controlled, double-blinded, single ascending dose design. MAU868 was safe and well-tolerated. All adverse events were Grade 1 and resolved. The pharmacokinetics of MAU868 was typical of a human IgG, with dose-proportional systemic exposure and an elimination half-life ranging between 23 and 30 days. These results demonstrate the potential of MAU868 as a first-in-class therapeutic agent for the treatment or prevention of BKPyV disease.

Considerations for the care of transgender patients in orthopaedics and sports medicine: a narrative review.

Orthopaedic and sports medicine clinicians can improve outcomes for transgender patients by understanding the physiological effects of gender-affirming hormone therapy (GAHT). This narrative review investigated the role of GAHT on bone mineral density, fracture risk, thromboembolic risk, cardiovascular health and ligament/tendon injury in this population. A search from the PubMed database using relevant terms was performed. Studies were included if they were levels 1-3 evidence. Due to the paucity of studies on ligament and tendon injury risk in transgender patients, levels 1-3 evidence on the effects of sex hormones in cisgender patients as well as basic science studies were included for these two topics. This review found that transgender patients on GAHT have an elevated fracture risk, but GAHT has beneficial effects on bone mineral density in transgender women. Transgender women on GAHT also have an increased risk of venous thromboembolism, stroke and myocardial infarction compared with cisgender women. Despite these elevated risks, studies have found it is safe to continue GAHT perioperatively for both transgender women and men undergoing low-risk operations. Orthopaedic and sports medicine clinicians should understand these unique health considerations for equitable patient care.

Novel calibration design improves knowledge transfer across products for the characterization of pharmaceutical bioprocesses.

Modern machine learning has the potential to fundamentally change the way bioprocesses are developed. In particular, horizontal knowledge transfer methods, which seek to exploit data from historical processes to facilitate process development for a new product, provide an opportunity to rethink current workflows. In this work, we first assess the potential of two knowledge transfer approaches, meta learning and one-hot encoding, in combination with Gaussian process (GP) models. We compare their performance with GPs trained only on data of the new process, that is, local models. Using simulated mammalian cell culture data, we observe that both knowledge transfer approaches exhibit test set errors that are approximately halved compared to those of the local models when two, four, or eight experiments of the new product are used for training. Subsequently, we address the question whether experiments for a new product could be designed more effectively by exploiting existing knowledge. In particular, we suggest to specifically design a few runs for the novel product to calibrate knowledge transfer models, a task that we coin calibration design. We propose a customized objective function to identify a set of calibration design runs, which exploits differences in the process evolution of historical products. In two simulated case studies, we observed that training with calibration designs yields similar test set errors compared to common design of experiments approaches. However, the former requires approximately four times fewer experiments. Overall, the results suggest that process development could be significantly streamlined when systematically carrying knowledge from one product to the next.