Kurnool, India

Open-label Study to Evaluate Metreleptin in Patients With Partial Lipodystrophy

Application of Plant Protection Products (PPP) in Apple Orchards

A Non-interventional Study for Kisqali (Ribociclib) in Combination With an Aromatase Inhibitor for Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer at High Risk of Recurrence

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an non-steroidal aromatase inhibitor (NSAI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the German summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the respective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + NSAI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + NSAI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and optionally Austrian and Swiss breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + NSAI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

Adjusted High-dose Chemotherapy with Autologous Stem Cell Transplant Vs. Conventional Immunochemotherapy in Elderly PCNSL Patients

Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare lymphoma affecting only the central nervous system compartment. PCNSL patients are typically 60 years or older and have poor prognoses. However, there are alternative treatment approaches to consider with the potential to improve medical outcomes for this patient population. The current standard of care in Germany and many international centres for patients 65 and older is treatment with R-MP, comprising rituximab, high-dose methotrexate (HD-MTX) and procarbazine followed by maintenance therapy with procarbazine. An alternative approach comprised of a shorter induction treatment with rituximab, HD-MTX and cytarabine (MARTA) followed by age-adjusted high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) was recently shown to be feasible and effective in elderly PCNSL patients considered eligible for high-dose chemotherapy requiring autologous stem cell transplantation. Nevertheless, data evaluating this short duration treatment approach remains scarce, and randomized trials have not yet been published. The objective of the PRIMA-CNS trial is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with R-MP followed by maintenance with procarbazine in elderly patients with newly diagnosed PCNSL; not only regarding survival and remission after treatment but also regarding standards like quality of life (QOL) and treatment related morbidities. Results of this randomized trial will either change the standard of care to an intense and shorter treatment approach or re-define R-MP as a proven treatment standard. In addition, a geriatric assessement is implemented in this trial with the goal to better define transplant eligibility. If this trial shows the superiority of HCT-ASCT, the investigators will establish an improved treatment standard with increased chances for long-term remission and cure and reduced frequency and length of chemotherapy treatment. Considering the poor prognosis of this patient population, this randomized phase III trial is of great clinical importance to provide patients, the patients' families and care takers with optimal treatment.

Troubled-Desire & Therapeutic Chat for Reduction of CSAM Use (TD-CHAT)

The study will evaluate whether the TCS intervention and Selfhelp modules, independently or combined, effectively reduce CSAM use or risk of CSAM consumption and improve mental well-being among self-referred participants. 1. Objectives 1.1 Primary objectives 1. To compare the effectiveness in reducing CSAM behaviours between the TD only group and the waitlist group four weeks after the baseline assessment. 2. To compare the post-intervention effectiveness in reducing CSAM behaviours of the Selfhelp modules versus TCS alone and Selfhelp modules followed by TCS. 1.2 Secondary objectives 1. To assess the reduction in severity, time and self-rated risk of CSAM consumption among participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) compared to the waitlist control group, at post-intervention. 2. To compare the impact of the interventions (Selfhelp modules, TCS, or Selfhelp + TCS) on mental wellbeing, in contrast to the control group, at the end of the intervention period. 3. To evaluate the effect of the interventions (Selfhelp modules, TCS, or Selfhelp + TCS) on total sexual outlet compared with the waitlist control group after the intervention period. 4. To identify any adverse effects associated with the interventions (Selfhelp modules, TCS, or Selfhelp + TCS). 2. Hypotheses 2.1 Primary hypothesis 1. Participants in the Selfhelp-only modules group will show a statistically significantly higher proportion of reduction in CSAM behaviours four weeks after baseline, as compared to participants in the waitlist control group. 2. Participants in the Selfhelp modules followed by TCS group will show a statistically significantly higher reduction of CSAM behaviours compared to participants in the Selfhelp-only and TCS-only groups, post-intervention. 2.2 Secondary hypothesis 1. Participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will show a statistically significant reduction in the severity, time and self-rated risk of CSAM consumption compared to participants in the waitlist control group, four weeks after the initial intervention. Among the intervention groups, it is expected that the Selfhalp + TCS group will show the greatest reduction in CSAM consumption, followed by the TCS group and then the Selfhelp-only group. 2. Participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will show a statistically significant improvement in their mental well-being (measured using the Warwick-Edinburgh Mental Wellbeing scale). compared to participants in the waitlist control group, at post-intervention. Among the intervention groups, the Selfhelp + TCS group is expected to show the greatest improvement, followed by the TCS group, and then the Selfhelp-only group. 3. Participants in the intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will show a statistically significant reduction in total sexual outlet (measured using a self-reported measure) compared to participants in the waitlist control group, after the intervention. Among the intervention groups, the Selfhelp + TCS group is expected to show the greatest reduction, followed by the TCS group, and then the Selfhelp-only group. 4. All intervention groups (Selfhelp modules, TCS, or Selfhelp + TCS) will experience adverse effects (psychological and emotional distress) to a similar extent, with no significant differences in the number or type of adverse effects reported. Adverse effects are expected to primarily involve mild to moderate psychological and emotional distress, such as feelings of anxiety or frustration, but are not expected to lead to severe distress or long-term harm. 3.Trial design This is a prospective, randomised, multicentre, open-label, parallel-group, superiority trial designed to compare stratified, pair-matched CSAM users across three intervention groups and one wait-list control group, with an allocation ratio of 1:1:1:1. Following participant agreement to the terms of the study, demographic information, measures for stratified randomization, and baseline outcome data will be collected. Additionally, data collected from the four groups Selfhelp modules, TCS, Selfhelp + TCS, and waitlist) of the TD-CHAT study will be compared with data from a fifth group (waitlist + TCS) sourced from the "Scalable Technology for Online Prevention of Child Sexual Abuse and Child Sexual Abuse Materials" (STOP-CSAM) project.

Amplitude-modulated Radiofrequency Electromagnetic Field Treatment for Advanced Hepatocellular Carcinoma (Immune-RF)

Charité University Medicine Berlin is currently the only German University Hospital with an available capacitive radiofrequency electromagnetic field treatment device. While there is retrospective data available regarding the assumed effectiveness and low toxicity profile of radiofrequency electromagnetic field treatment for various solid tumors including liver cancer, there is no prospective data available on the combined effect of first-line palliative double immune checkpoint inhibition and radiofrequency electromagnetic field treatment for patients with advanced hepatocellular carcinoma. The investigators aim to conduct a feasibility trial and plan to compare the results with data of a prospective trial with a comparable patient population who received double immune checkpoint inhibition alone.

Developing a Patient-Reported Outcome (PRO) Screening Measure for Infections and Measuring Quality of Life in Hematological Patients With Secondary Immunodeficiency (SID) Across the Treatment Trajectory - The PRO SID Project

The aim of this observational study is to develop an ePRO symptom monitoring tool to identify infections among patients with MM or CLL who recently started an anticancer therapy. This multicenter trial, conducted in participating sites in Germany in Austria, targets a total of 120 adult patients to complete daily ePRO questions in a mobile app regarding current infection-related symptoms. Objectives: Primary: To develop and evaluate the diagnostic accuracy of a newly developed PRO screening measure for detecting clinically diagnosed infections in hematological patients with SID. Secondary: To measure QoL over time using validated instruments such as the EORTC QLQ-C30 and disease-specific modules (QLQ-MY20 for MM and QLQ-CLL17 for CLL). Explore whether PRO-based infection detection prompts subsequent initiation of immunoglobulin replacement therapy (IgRT) and examine QoL before and after its initiation. Exploratory Objectives: - To evaluate the completion and adherence rates for ePRO assessments. - To investigate the predictive value of the PRO screening tool for infection incidence. To develop a reliable item list to monitor and detect infections, it is necessary to establish a high-quality measurement of infections as criterion. We developed the item list based on items from the European Organisation for Research and Treatment of Cancer (EORTC) Item Library and in line with international best-practice recommendations for item list development. The development comprised a comprehensive review of the literature and existing measures measuring infection-related symptoms, as well as physician input on which domains and symptoms were the most relevant to assess to monitor for infections in this population. Clinicians will also document any diagnosed infections and relevant clinical data throughout study visits, which take place every three months. These include updates on treatment regimens, disease staging, and infection history. The app was developed based on the Computer-based Health Evaluation System (CHES) software platform, which allowed for real-time symptom tracking and data integration. The software has been used extensively and also been tested with patients with hematological diseases in the past. For the PRO-SID app, we developed study-specific content, which comprised information in lay language on the diseases (MM and CLL), information on infections and SID, and information on the study itself. The native app (iOS and Android) prompts patients to complete the item list once daily via push-reminders (up to two reminders). Usability of the app and understanding of the item list within the daily ePRO assessment on infection symptoms has been assessed within a designed feasibility study according to best practice guidelines (data to be published separately). After completion of the feasibility study, we implemented changes to the app based on patients' feedback and answers in the evaluation questionnaires in order to improve the app for the final study. Patient Safety and Ethics: The study is conducted in compliance with the Declaration of Helsinki and Good Clinical Practice standards. Informed consent is obtained, and all participant data is de-identified and securely stored to ensure confidentiality.

A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants

Clinical Study to Predict the Risk of Bone Fractures With the POROUS Ultrasound Device

Background and purpose: Currently, osteoporosis and fracture risk are indirectly evaluated via the assessment of risk factors and bone mineral density (BMD) measurement. Although BMD is currently the most important indicator for osteoporosis-associated bone fractures, most of those fractures occur in persons who do not show pathologically reduced BMD value. Therefore, osteoporosis is one of the most frequently underdiagnosed common diseases. Established guidelines for the diagnosis of osteoporosis recommend the assessment of fracture risk factors and the T-Score, which is derived from the measurement of areal bone mineral density (aBMD) by means of DXA at major fracture sites, i.e., spine and proximal femur. DXA is regarded as the "gold standard" well-established methodology to determine aBMD for diagnostic purposes. Epidemiological data emphasize the urgency of developing diagnostic tools that can improve fracture risk prediction so that patients can be treated with the appropriate anti-osteoporotic therapies. Current guidelines for diagnosis and treatment lead to treatment gaps. It is estimated that at least 80% of males and 77% of females who would benefit from osteoporosis treatment are neither diagnosed nor treated in Germany. Device description: The POROUS R3C ultrasound device enables a non-invasive, non-ionizing quantitative detection of microstructural bone changes. As opposed to diagnosis based on a combination of clinical risk factors and a relative decrease of BMD, the novel device enables detecting pathological changes of bone microstructure at an earlier timepoint as well as monitoring such changes in a longitudinal manner. In the course of this clinical investigation, data will be collected to establish relevant ultrasound-based physical biomarkers for the prediction of fracture risk. Study design: This is a single-cohort, multicenter, prospective, age- and sex-stratified study in participants > 55 years of age. In this study, Baseline data will be collected to establish a corrected standardized gradient of fracture risk using the POROUS R3C ultrasound device and test its performance in predicting fracture risk. Further, the performance of the POROUS R3C ultrasound device in the analysis of cortical bone properties and discrimination of prevalent fractures will be assessed. Participants will be enrolled into different groups based on their age (consisting of five-year bands), sex (males and females), and risk status for hip and vertebral fractures (i.e., high risk of ≥ 2-fold and low risk of < 2-fold increased risk compared to the general population of the same age and sex). Two measurements with each device: investigational device (POROUS R3C ultrasound device at the midshaft tibia), and comparator (DXA of the lumbar spine and proximal femur), are scheduled per participant: - Measurement 1: At Baseline - Measurement 2: At the End-of-Study (EoS) visit. Study Part 1: In Part 1, information on prevalent fractures will be used to establish a corrected standardized gradient of fracture risk using the POROUS R3C ultrasound device. In other words, Part 1 aims to establish the discriminative performance and a standardized gradient of fracture risk based on prevalent fractures. In addition, the discriminative performance of the POROUS R3C ultrasound device and standard-of-care DXA will be compared based on prevalent fractures. Study Part 2: In Part 2, information on incident fractures will be used to establish a corrected standardized gradient of fracture risk using the POROUS R3C ultrasound device. It will be developed to demonstrate the predictive performance of the derived fracture risk. In other words, Part 2 aims to establish a standardized gradient of fracture risk based on incident fractures. In addition, the predictive performance of the POROUS R3C ultrasound device and standard-of-care DXA will be compared based on incident fractures. The collection of data obtained by DXA and the POROUS R3C device at the EoS visit is used to monitor changes in the bone state in comparison to the respective data obtained at Baseline. However, only measurement data obtained by the POROUS R3C device at Baseline is used to develop the POROUS-Score model and the standardized gradient of fracture risk (for Part 1 and Part 2). Primary objectives: - Part 1 -To establish a corrected standardized gradient of fracture risk using the POROUS R3C ultrasound device based on prevalent fractures. - Part 2 - To establish a corrected standardized gradient of fracture risk using the POROUS R3C ultrasound device based on incident fractures and to demonstrate the predictive performance of the derived fracture risk. Secondary objectives: - Part 1 - To compare the discriminative performance of the POROUS R3C ultrasound device and standard-of-care DXA based on prevalent fractures. - Part 2 - To assess the safety of the POROUS R3C ultrasound device by monitoring adverse events affecting participants or the healthcare professionals using the device. - Part 2 - To compare the predictive performance of the POROUS R3C ultrasound device and standard-of-care DXA based on incident fractures. Exploratory objectives: - Part 1 - To assess the association of various ultrasound parameters measured by the POROUS R3C ultrasound device with specific clinical risk factors/indicators for vertebral and hip fractures (as outlined by the DVO) and prevalent fractures. - Part 1 - To demonstrate the discriminative performance of the POROUS R3C ultrasound device based on subgroups of prevalent fractures, e.g., hip, vertebral, and major osteoporotic fractures. - Part 1 - To establish reference data for developing age-adjusted POROUS Z-scores using the POROUS R3C ultrasound device based on prevalent fractures. - Part 2 - To assess the association of various ultrasound parameters measured by the POROUS R3C ultrasound device with specific clinical risk factors/indicators for vertebral and hip fractures (as outlined by the DVO) and incident fractures. - Part 2 - To demonstrate the predictive performance of the POROUS R3C ultrasound device based on subgroups of incident fractures, e.g., hip, vertebral, and major osteoporotic fractures. - Part 2 - To establish reference data for developing age-adjusted POROUS Z-scores using the POROUS R3C ultrasound device based on incident fractures. - Part 2 - To explore the treatment effect of anti-osteoporotic medication - Part 2 - To explore the treatment effect of drugs known to influence bone metabolism. Participants: A total of 1,600 female and male participants (> 55 years of age) will be included in the investigation. This population is planned to include 1,120 participants with ≥ 2-fold increased age- and sex-adjusted risk for hip and vertebral fractures and 480 participants with a < 2-fold increased age- and sex-adjusted risk for hip and vertebral fractures. Stratification of participants, fracture risk < 2-fold increased risk: - Age group 56-60, males/females = 40 per group, total = 80. - Age group 61-65, males/females = 40 per group, total = 80. - Age group 66-70, males/females = 40 per group, total = 80. - Age group 71-75, males/females = 40 per group, total = 80. - Age group 76-80, males/females = 40 per group, total = 80. - Age group 81-85, males/females = 40 per group, total = 80. Stratification of participants, fracture risk ≥ 2-fold increased risk: - Age group 66-70, females = 100 per group. - Age group 71-75, males = 100 per group, females = 160 per group, total = 260. - Age group 76-80, males/females = 180 per group, total = 360. - Age group 81-85, males/females = 200 per group, total = 400. The expected number of incident fractures* ~140 (at 24 months), ~210 (at 36 months). *The assumed number of fractures per analysis group (DXA and POROUS R3C) at Month 24 and Month 36, respectively, is based on age- and sex-matched incidence rates for fractures (Rupp et al., Deutsches Ärzteblatt International, 2021), further updated by data on the incidence of vertebral fractures (Fink et al., JBMR, 2005). Risk calculation for hip and vertebral fractures: At Screening, assessment of clinical risk factors and application of risk calculating scheme as outlined in the Dachverband Osteologie (DVO, tri-national umbrella association of German, Austrian, and Swiss medical and scientific professional societies in the field of bone diseases) osteoporosis guideline will determine whether a participant is at increased risk (≥ 2-fold compared to the general population of the same age and sex) for hip and vertebral fractures. Please note that the calculation of the pertinent risk as performed in this study does not include any DXA-based BMD measurements and T-Scores. No DXA BMD measurement or DXA-based vertebral fracture assessment (VFA) will be conducted at Screening. Noteworthy, DXA-based BMD measurement results and T-Scores will be included in the different analyses of the study endpoints but not for the risk calculation at Screening as described above. Screened and eligible individuals will be enrolled in the investigation until the necessary sample size for his/her corresponding group (based on age, sex, and risk status) has been reached (see Table below). To avoid over-recruiting, once the necessary sample size for one group has been reached, no further individuals with matching age band, sex, and risk status will be enrolled in the study. Duration of the study: The planned overall clinical investigation is expected to take 48 months, including an enrolment period of approximately 12 months and a clinical investigation period of 36 months. Per participant, the total time of participation in the investigation will take 36 months. 20 months (+/-1 month) after the first participant has been included in the investigation, a checkpoint assessment of the number of fracture events so far recorded is planned. The aim is to assess whether the number of fractures projected to be reached after each participant will have been followed-up for 24 months would be sufficient for a test of the primary endpoint with sufficient statistical power. If this is the case, the clinical investigation period will be shortened to 24 months (correspondingly, the overall duration will be shortened to 36 months). If, at the checkpoint assessment, the number of fractures is insufficient, the follow-up period will remain as planned and the EoS visit will take place at 36 months, amounting to the originally planned overall duration of 48 months. Duration of participation: The total time of participation in the investigation will take 36 months per participant, with the option to be shortened to an investigational period of 24 months based on the results of a checkpoint assessment of reported fractures scheduled at Month 20 (+/-1 month). Fracture risk prediction model: The diagnostic value of physical biomarkers, which are derived from Baseline measurements with the POROUS R3C ultrasound device, will be assessed, and selected physical biomarkers will be integrated into a model, resulting in a composite POROUS-Score, for fracture risk prediction. In Part 1, the model will be developed using data on prevalent fractures, while in Part 2, the model will be developed using data on incident fractures. The resulting POROUS-Scores are, therefore, different in Part 1 and Part 2. In Part 1, it is termed POROUS-Score(Prev), whereas in Part 2, it is termed POROUS-Score. Additionally, anthropometric data (age, sex, and BMI) will be evaluated and selected for adding predictive strength to the prediction model. Part 1: Prevalent fractures will be recorded, and all relevant variables, including ultrasound parameter values and anthropometric information, will be used to perform partial least squares - discriminant analysis (PLS-DA) followed by subwindow permutation analysis using a Monte-Carlo approach. Only variables that have statistically significant discriminative power will be used in the next step, where a new fracture discrimination model will be created using PLS-DA analysis. Thereafter, the performance of the model will be investigated using receiver operating characteristics (ROC) analysis. More precisely, logistic discriminant analysis will be performed. Area under the curve (AUC) values and their confidence intervals will be computed from ROC curves for each model. Internal validation of the model will be performed by using cross-validation followed by bootstrap analysis. Odds ratios will be determined for both the final composite POROUS-Score(Prev) (generated from the internally validated model) and DXA T-Score. Standardized odds ratios (sOR) will be calculated, i.e., the fold-increase of the relative fracture risk per standard deviation decrease of the respective score. The discriminative ability of the POROUS model for prevalent fractures is demonstrated if the lower limit of the 90% confidence interval of the corrected sOR is higher than 1. Part 2: Incident fractures will be recorded, and all relevant variables, including ultrasound parameter values and anthropometric information, will be used to perform PLSDA followed by sub-window permutation analysis using a Monte-Carlo approach. Only variables that have statistically significant predictive power will be used in the next step, where a multivariate Cox-proportional Hazard model will be performed to calculate the hazard ratio (HR). Then, the model performance will be investigated using ROC analysis. Internal validation of the model will be done by running cross-validation followed by Bootstrap analysis. The standardized relative risk (sRR) will be calculated, i.e., the fold-increase of the relative fracture risk per standard deviation decrease of the respective score. The sRR will be determined for both the final composite POROUS-Score (generated from the internally validated model) and DXA T-Score. The predictive ability of the POROUS model for incident fractures is demonstrated if the lower limit of the 90% confidence interval of the corrected sRR is higher than 1. Clinical procedures: The following clinical procedures are performed during the investigation: Screening - Informed consent - Inclusion/exclusion criteria - Calculation of individual risk for hip and vertebral fractures as per modified version of the DVO risk calculation scheme (excluding DXA-based BMD measurement and T-Score) - Enrolment into corresponding age-sex-risk group. Baseline (Visit 2, 0-14 days after Screening) - Scanning with the POROUS R3C ultrasound device at the central anteromedial tibia region - Scanning with DXA (aBMD of the lumbar spine and proximal femur). - Fracture anamnesis, including DXA-based VFA. Alternatively, VFA may be replaced by projectional radiography if VFA is not available. - Assessment of clinical risk indicators (as per DVO guideline) - Assessment of concomitant medication (initiation of anti-osteoporotic medication as well as oral glucocorticoids, proton pump inhibitors, aromatase inhibitors, hormone ablation therapy/antiandrogens in males). - Recording of adverse events. Follow-up period Interim visits (phone survey) - Visits 3-7 at Month 6, 12, 18, 24, 30 ± 14 days - Assessment of incident fractures (to be validated by requesting medical documents - X-ray images, physician's findings) - Concomitant medication assessment - Recording of adverse events Early-termination (ET) visit/phone survey Participants who withdraw early (i.e., before undergoing the EoS visit) will be offered an ET clinical visit, including - VFA (or projectional radiography of the spine, respectively, if VFA is not available) - Anamnesis of incident fractures since the last visit/phone survey - Concomitant medication assessment (see above) - Recording of adverse events. (Alternatively, the visit can be conducted as a phone survey if the time gap since the last DXA/VFA is < 6 months or the participant is not available for a clinical visit). EoS visit - Visit 8 at Month 36 ± 14 days - Scanning with the POROUS R3C ultrasound device at the central anteromedial tibia region - Scanning with DXA (aBMD of the lumbar spine and proximal femur). - Assessment of incident fractures including VFA (or projectional radiography of the spine) - Re-assessment of fracture risk factors/indicators as per DVO guideline and recalculation of risk for hip and vertebral fractures - Concomitant medication assessment - Recording of adverse events. Subgroup analysis: General subgroups for analyses are defined based on age, sex, and risk (for hip and vertebral fractures). Stratification groups are presented in the table on "Number of participants to be included in the investigation" included above. In addition, subgroup analyses are done to monitor treatment effects, as described in the exploratory endpoint of Part 2.