bluuebunny/crossref_metadata_2025 huggingface dataset:
TCF-001 TRACK (Target Rare Cancer Knowledge): A national patient-centric precision oncology trial for rare cancers.
Authors: Subbiah Vivek , Groisberg Roman , Skefos Catherine , Cleary James M. , Subbiah Ishwaria Mohan , Palma Jim , Oster Mary , Young Steven W. , Elvin Julia Andrea , Sicklick Jason K. , Gaffey Sarah , Ward Ashley , Alexander Brian Michael , Lee J. Jack , De Pradip , Kato Shumei , Kurzrock Razelle
Published: June 2021

TPS3143

Background: Many rare cancers are understudied, and affected patients often have few if any standard treatment options and limited access to clinical trials. Comprehensive genomic profiling (CGP) is a robust tool to efficiently identify the genomic alterations of cancer and can be applied to study rare tumors. The promise of this technology is to simultaneously enhance our understanding of diverse rare tumors and find matched therapies to benefit the individual patient in real-time. The COVID19 pandemic has challenged the “trial-centric” clinical trial infrastructure. Novel “patient-centric” trials are needed, especially for rare cancers. TRACK is a decentralized, patient advocacy-initiated trial that aims to establish whether patients with rare tumors and cancer of unknown primary can benefit from matched molecular therapy as dictated by their CGP results. Methods: This is a national open label, non-randomized, multi-center (includes community and academic centers) pragmatic study in rare tumors (<6 cases per 100,000 persons per year) and cancer of unknown primary. All participants will have tumor tissue and blood analyzed by CGP (FoundationOneCDx and FoundationOneLiquidCDx). A Virtual Molecular Tumor Board (VMTB) will convene to identify targeted treatment recommendations for participants with genomic alterations. Overall, 400 participants will be enrolled to achieve the goal of 100 patients matched to genomically informed treatment, utilizing remote consenting to ensure study access regardless of geographic location. The primary feasibility endpoint is the percent of participants who receive a molecularly matched treatment after recommendation from the VMTB. The primary efficacy endpoint is the progression-free survival (PFS) among participants who received the molecularly matched treatment. Secondary endpoints include the percent of participants with genomic alterations, overall response rate, response duration, overall survival, clinical benefit rate (SD > 6 months; PR; CR), and high-grade toxicities (as available) of matched targeted therapy. Exploratory endpoints include matching rates; understanding genomic correlates of response; concordance rates between CGP from tissue and blood, time-to-treatment failure, and the impact of the cancer treatment from the patient perspective (via ESAS-FS, a validated patient-reported outcomes (PRO) instrument). All eligible and enrolled patients, regardless of whether receiving matched treatment or not, will be followed for a minimum of one year in a uniform way such that the treatment efficacy and outcomes can be assessed in standard formats. The study is open with six patients enrolled at time of submission. Clinical trial information: NCT04504604.
Total neoadjuvant treatment versus standard chemoradiation to increase the sphincter preservation rate for distal locally advanced rectal cancer (TESS).
Authors: Xiao Weiwei , Wu Xiaojun , Cai Peiqiang , Zhuang YeZhong , Wang Xiaozhong , Bai Shoumin , Wang Qiaoxuan , Ye YiJing , Liu Qing , Liu Min , Liu Shuang , Zeng ZhiFan , Pan Zhi-Zhong , Gao Yuanhong , Chen Gong
Published: June 2021

TPS3615

Background: Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with radiotherapy, followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant chemoradiotherapy to decrease surgical morbidity and increase quality of life. RAPIDO and PRODIGE-23 trials showed that TNT strategy could improve the pathological complete response (pCR) rateand reduce the risk of distant metastasis. The objective of this trial is to increase the proportion of sphincter preservation rate for distal rectal cancer patients by optimizing tumor response, by using TNT regimen as compared to conventional chemoradiotherapy. TESS (clinicalTrials.gov, NCT03840239), a prospective, open label, multicenter, randomized phase 2 study, is underway. Methods: Main inclusion criteria include: cT3-4aNany or cTanyN+ rectal adenocarcinoma aged 18-70y; ECOG performance 0-1; distance≤5cm from anal verge. 168 patients will be randomized 1:1. Patients in the TNT group will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplation) before, during and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as watch and wait) and adjuvant chemotherapy capecitabine 2 cycles. Patients in the standard treatment group will receive neoadjuvant radiotherapy 50Gy/25 fractions combined with capecitabine 5 weeks before TME (or other treatment decisions, such as watch and wait), and adjuvant chemotherapy Capeox 6 cycles. Primary endpoint is the rate of sphincter preservation rate (absence of stoma). Secondary endpoints include: Ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; acute toxicity; surgical complications; long-term anal function; late toxicity; ECOG standard score; disease-free survival; overall survival. First site opened in January 24, 2019. Clinical trial information: NCT03840239.
A multicenter, randomized phase 1b/2 study of gemcitabine and cisplatin with or without CPI-613 as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-04).
Authors: Sahai Vaibhav , Chang Amy E. , Crysler Oxana V. , Zhen David Bing , Beg Muhammad Shaalan , Pardee Timothy S. , Luther Sanjeev , Griffith Kent A. , Zalupski Mark
Published: June 2021

TPS4158

Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis despite systemic chemotherapy. Gemcitabine and cisplatin is a standard first-line systemic therapy with an overall response rate (ORR) of 26% and a median overall survival of 11.7 months. This investigator-initiated, multi-institutional phase 1b/2 trial is designed to investigate the role of gemcitabine, cisplatin and CPI-613 in pts with advanced BTC. CPI-613 is a stable intermediate of a lipoate analog that inhibits pyruvate dehydrogenase and a-ketoglutarate dehydrogenase enzymes of the tricarboxylic (TCA) cycle preferentially within the mitochondria of cancer cells. Methods: Key eligibility criteria include histologically confirmed, metastatic or unresectable BTC (intra- or extra-hepatic and gallbladder) without prior systemic treatment, measurable disease per RECIST v1.1, and ECOG PS 0-1. Primary objective of the phase 1b portion (n = 20 pts; TiTE-CRM methodology) is to determine the recommended phase 2 dose of the combination, and for the phase 2 portion, ORR (n = 48-58 pts; 2:1 randomization). Assuming a null hypothesis ORR of 25% and an alternative hypothesis of 43%, this ongoing trial has at least 80% power with a one-sided alpha of 0.05 to identify treatment efficacy of the study arm. Secondary objectives include evaluation of progression-free survival, overall survival, and safety in this patient population. Exploratory objectives include identification of molecular markers of response and resistance in tumor samples and serially collected blood (pre-, on-, and post-therapy), including whole exome/transcriptomic analysis, and immunohistochemical staining (PDK, PDH, KGDH, SOD2 and CD79a). Gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 with or without CPI-613 (dose levels: 500 mg/m2, 1000 mg/m2, 1500 mg/m2, and 2000 mg/m2) will be given IV on days 1 and 8 every 21 days. In the absence of disease progression, pts may continue therapy for up to 2 years. Total accrual goal is 68-78 evaluable pts. To date, 5 of planned 20 pts enrolled on the phase 1b portion are without dose limiting toxicity. Clinical trial information: NCT04203160.
The IMMULAB trial: A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC).
Authors: Vogel Arndt , Goetze Thorsten Oliver , Hausner Guido , Geißler Michael , Siegler Gabriele Margareta , Fischer von Weikersthal Ludwig , Kestler Angelika M. R. , Kleiß Matthias , Müller Tobias , Teufel Andreas , Marquardt Jens , Gonzalez-Carmona Maria A , Mueller Daniel Wilhelm , Eickhoff Regina , de Toni Enrico N. , Waidmann Oliver , Al-Batran Salah-Eddin
Published: June 2021

TPS4159

Background: The investigator-initiated IMMULAB study investigates the clinical activity of peri-interventional treatment with the anti-PD1 antibody pembrolizumab in HCC patients who are candidates for local ablation via either radiofrequency ablation (RFA), microwave ablation (MWA) or brachytherapy, or - as recommended for tumor larger than 3 cm – by combination with TACE. Patients with extrahepatic disease are excluded. Local ablation is known to induce tumor destruction with subsequent antigen release resulting in host adaptive immune responses. However, tumors could quickly overcome the immune responses by upregulating PD-L1/PD-1 expression and inhibiting the function of CD8+ and CD4+ T cells. Thus, combination of local ablation with an anti-PD1 antibody might display interesting effects by activating immune cells and disabling immune inhibitory mechanisms at the same time. Methods: This is a prospective investigator initiated single-arm multicenter phase II trial investigating immunotherapy with the PD-1 inhibitor pembrolizumab in combination with local ablation in early stage hepatocellular carcinoma (HCC). Patients with a child-pugh classification score ≤ 6, including high risk candidates for local ablation (defined as patients having ≤ 5 tumor nodules with diameters ≤ 7cm [longest axis] each OR patients with vascular infiltration) receive 200mg pembrolizumab i.v. q3w for 2 cycles. Thereafter, radiologic imaging is followed by local ablation on day 1 of cycle 3. Further pembrolizumab (200mg) is applied 2 days after ablation and thereafter every 3 weeks (q3w) for a total treatment duration of up to 12 months. It is planned to enroll 30 pts. Primary efficacy endpoint is the overall response rate (RECIST 1.1) after 2 cycles of pembrolizumab and before performing local ablation aiming in the conversion / downstaging of borderline candidates by pre-interventional treatment with pembrolizumab. Overall recruitment has started; currently (Feb 2021) 18 of 30 planned patients have been enrolled. Clinical trial information: NCT03753659.
Total neoadjuvant FOLFIRINOX or gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2): A nationwide multicenter randomized controlled trial.
Authors: Janssen Quisette , van Dam Jacob L. , Besselink Marc G.H. , Homs Marjolein Y.V. , van Tienhoven Geertjan , Wilmink Johanna W. , Groot Koerkamp Bas ,   Dutch Pancreatic Cancer Group
Published: June 2021

TPS4171

Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials (including the Dutch PREOPANC trial) have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including gemcitabine-based chemoradiotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether total neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine (i.e. the intervention arm of the PREOPANC trial) in patients with resectable or borderline resectable pancreatic cancer. Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) added during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients, assuming an accrual period of 3 years and 1.5 years follow-up. Between June 2018 and January 2021, 375 patients were enrolled in 20 centers in the Netherlands and accrual is complete. Final analyses are expected at the end of 2022. Netherlands Trial Register: NL7094. Clinical trial information: NL7094.
A phase I study of bintrafusp alfa (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies.
Authors: Niglio Scot Anthony , Girardi Daniel da Motta , Cordes Lisa M. , Ley Lisa , Mallek Marissa , Sierra Ortiz Olena , Cadena Jacqueline , Diaz Carlos , Chalfin Heather , Kydd Andre , Costello Rene , Marciscano Ariel E. , Jones Jennifer C , Salerno Kilian Elizabeth , Valera Vladimir , Figg William Douglas , Dahut William L. , Gulley James L. , Schlom Jeffrey , Apolo Andrea B.
Published: June 2021

TPS4599

Background: The majority of non- prostate genitourinary (GU) cancers are lethal when metastatic and rare GU cancers have limited treatment options. Bintrafusp alfa is a bifunctional fusion protein composed of human TGF-β receptor II, which sequesters or “traps” all three TGF-β isoforms and a monoclonal PD-L1 antibody. NHS-IL12 is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor with DNA exposure to promote local immunomodulation. Preclinical data suggest synergy between these two agents. There is also evidence suggesting that stereotactic body radiation therapy (SBRT) can promote anti-tumor immune responses both locally and systemically while also synergizing with immune checkpoint inhibitors. Therefore, the combination of Bintrafusp alfa, NHS-IL12 and radiation is a potential strategy for metastatic non-prostate GU tumors. Methods: This is an open label, non-randomized, three-stage phase I trial of bintrafusp alfa and NHS-IL12 or bintrafusp alfa and NHS-IL12 in combination with either sequential or concurrent SBRT. Bintrafusp alfa (IV 1200 mg q2w) and SBRT (8 Gy x 3 fractions) are planned with a deescalating NHS-IL12 (subQ q4w) dose schedule. The accrual ceiling has been set at 66 patients. The trial will enroll patients with a pathologically confirmed diagnosis of metastatic non-prostate genitourinary cancer with an ECOG ≤ 2 (KPS ≥60%). Participants may have had prior cancer immunotherapy but excluding prior treatment with bintrafusp alfa and/or NHS-IL12. 9 patients will receive treatment in cycles consisting of 4 weeks. The primary objective is to determine the safety and highest tolerated doses with acceptable toxicity (recommended phase II dose) of bintrafusp alfa and NHS-IL12 alone or in combination with SBRT administered sequentially or concurrently in patients with metastatic non-prostate genitourinary cancers. Secondary objectives are objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory objectives are to determine peripheral immune modulation and the status of the immune microenvironment using cytokine analysis, circulating tumor cells, multiplex immunohistochemistry, T-cell receptor sequencing, and RNA-sequencing. The study is open and enrolling. Clinical trial information: NCT04235777.
A phase 2, two-stage study of avelumab and axitinib in patients with mismatch repair proficient (MMR-P) recurrent or persistent endometrial cancer (EC).
Authors: Lee Elizabeth Katherine , Xiong Niya , Tayob Nabihah , Krasner Carolyn N. , Buss Mary K. , Campos Susana M. , Wright Alexi A. , Liu Joyce F. , Shea Meghan , Yeku Oladapo O. , Castro Cesar Martin , Porter Rebecca L , Stover Elizabeth , Bouberhan Sara , Moroney John William , Cannistra Stephen A. , Penson Richard T. , Fleming Gini F. , Matulonis Ursula A. , Konstantinopoulos Panagiotis A.
Published: June 2021

TPS5609

Background: Despite significant strides in understanding the molecular pathogenesis of EC, there remain few effective therapies for recurrent disease. Deeper insight into the roles of disordered tumor vasculature and HIF1α- and VEGF-mediated immunosuppressive effects on myeloid-derived suppressor cells, T-cells, and PD-L1 expression contributed to the development of new targeted regimens. Activity of pembrolizumab and lenvatinib was demonstrated in a phase 2 trial in MMR-P EC (NCT02501096). By inhibiting VEGF receptor (VEGFR) and PD-L1 signaling, immunologically “cold” tumors may become inflamed. However, there are concerns regarding the toxicity of pembrolizumab/lenvatinib and alternatives are sought. The combination of the anti-PD-L1 antibody avelumab with axitinib, an inhibitor of VEGFR 1-3 and PDGFR with more potent IC50 inhibitory activity than lenvatinib, has also shown synergistic activity and is FDA approved as first line treatment for patients with renal cell cancer. We therefore hypothesized that this combination would be well tolerated and efficacious in recurrent MMR-P EC. Methods: This is an investigator-initiated, phase 2, two-stage single cohort trial evaluating avelumab with axitinib in recurrent or persistent EC. Participants must have MMR-P EC of any histology and have received at least one chemotherapeutic regimen, with no upper limit on the number of prior lines received. Prior use of immune checkpoint (IC) inhibitors is excluded. Treatment consists of avelumab 800mg IV every 2 weeks and axitinib 5mg orally twice daily. Co-primary endpoints are progression-free survival at 6 months (PFS6) and objective response rate by RECIST 1.1. Translational objectives include characterization of tumor-infiltrating lymphocytes, infiltrating myeloid cells, expression of IC markers, and whole exome sequencing to evaluate mutations in genes related to DNA repair and immunologic response. This is a two-stage design in the method of Sill et al, with 16 participants anticipated in stage 1 and 19 participants in stage 2, for a total of 35 participants. Accrual is ongoing. Clinical trial information: NCT02912572.
Subcutaneous daratumumab (DARA SC) plus lenalidomide versus lenalidomide alone as maintenance therapy in patients (pts) with newly diagnosed multiple myeloma (NDMM) who are minimal residual disease (MRD) positive after frontline autologous stem cell transplant (ASCT): The phase 3 AURIGA study.
Authors: Shah Nina , Patel Sharmila , Pei Huiling , Qi Ming , Krevvata Maria , Lin Thomas S. , Khare Vipin
Published: June 2021

TPS8054

Background: DARA, a human anti-CD38 IgGκ monoclonal antibody, is approved in many countries as monotherapy in relapsed/refractory MM (RRMM) and in combination with standard of care (SoC) in RRMM and NDMM. However, no clinical studies have yet compared DARA maintenance versus SoC maintenance. The ongoing phase 3 AURIGA study will evaluate the addition of DARA to lenalidomide maintenance among pts with NDMM who are MRD positive after SoC induction and ASCT. The primary endpoint is the conversion rate to MRD negativity after 1 year of maintenance therapy. Methods: This open-label, multicenter, randomized phase 3 study will enroll approximately 214 pts in the United States aged 18-79 years with NDMM who receive ≥4 cycles of induction followed by ASCT. Pts must enroll within 6 months of ASCT, be naïve for anti-CD38 treatment, have a very good partial response or better per IMWG criteria, and be MRD positive at a threshold of 10–5 by next generation sequencing (NGS) within 30 days of screening. Pts will be stratified by cytogenetic risk (high vs standard/unknown) and randomized 1:1 to 28-day cycles of lenalidomide maintenance (10 mg PO; D1-28 [dose increasing to 15 mg if tolerated]) ± DARA SC (DARA 1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology, Halozyme, Inc., San Diego, CA, USA; QW Cycle 1-2, Q2W Cycles 3-6, Q4W C7+). Treatment will continue for up to 36 cycles or until disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint is MRD conversion rate after 12 months of maintenance treatment, defined as the proportion of pts who achieve MRD negativity (10–5) by NGS. Additional MRD assessments occur after 18, 24, and 36 months of maintenance. While MRD negativity is associated with improved long-term outcomes for pts with MM and is an emerging, validated prognostic factor, this study is among the first to use MRD negativity as a primary study endpoint. Importantly, MRD negativity allows for earlier efficacy assessment than traditional endpoints such as progression-free survival (PFS) and overall survival (OS). Secondary endpoints include overall MRD conversion rate at any time, sustained MRD negativity lasting ≥12 months, PFS, OS, response rates, duration of complete response, changes in health-related quality of life, and safety. Due to the COVID-19 pandemic, this study has been amended to improve enrollment access by allowing up to 12 months from start of induction therapy to ASCT to mitigate against ASCT delays and to allow greater flexibility for screening and laboratory assessments. Clinical trial information: NCT03901963.
CONTACT-01: A phase III, randomized study of atezolizumab plus cabozantinib versus docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC) previously treated with PD-L1/PD-1 inhibitors and platinum-containing chemotherapy.
Authors: Neal Joel W. , Kundu Palak , Tanaka Tomohiro , Enquist Ida , Patel Sid , Balestrini Alessia , Wang Jin , Newsom-Davis Thomas , Goto Yasushi , Pavlakis Nick , Kim Sang-We
Published: June 2021

TPS9134

Background: Patients with mNSCLC who progress on anti–PD-L1/PD-1 therapy administered in combination with or after platinum-based chemotherapy (PBC) are mainly treated with docetaxel or pemetrexed monotherapy. These therapies only have modest clinical activity, leaving a high unmet medical need. Cabozantinib, a tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment and may enhance the efficacy of PD-L1/PD-1 inhibitors, offering a promising second/third-line therapeutic opportunity for patients with mNSCLC. In a Phase Ib multi-cohort study (COSMIC-021; NCT03170960), cabozantinib plus atezolizumab (anti–PD-L1) showed an acceptable safety profile and promising efficacy (ORR: 27%; mDOR: 5.7 mo [range: 2.6-6.9]; disease control rate [CR + PR + SD]: 83%) in 30 patients with mNSCLC who had progressed after prior anti–PD-L1/PD-1 therapy plus chemotherapy (Neal et al. J Clin Oncol 2020). The Phase III CONTACT-01 study will further evaluate the efficacy and safety of atezolizumab plus cabozantinib versus docetaxel monotherapy in patients with mNSCLC who have progressed during or after prior treatment with anti–PD-L1/PD-1 therapy and PBC. Methods: CONTACT-01 (NCT04471428) is a Phase III, multi-center, randomized, open-label study that will enroll ≈350 patients from 150 to 200 sites internationally. Key eligibility criteria include histologically or cytologically confirmed mNSCLC, disease progression with concurrent or sequential anti–PD-L1/PD-1 treatment and PBC, measurable disease (RECIST 1.1), ECOG PS of 0-1 and the availability of tissue specimens for centralized PD-L1 testing or known PD-L1 status using a health authority–approved PD-L1 assay. Patients with NSCLC previously treated with cabozantinib, docetaxel or anti–PD-L1/PD-1 + VEGFR TKIs are excluded. Patients with known sensitizing EGFR/ALK mutations and active or untreated CNS metastases are also excluded. Patients will be randomized 1:1 to receive either atezolizumab (1200 mg IV every 3 weeks) + cabozantinib (40 mg orally once daily) or docetaxel (75 mg/m2 IV every 3 weeks). The primary endpoint is OS. Secondary endpoints include investigator-assessed PFS, ORR and DOR per RECIST 1.1; TTD in patient-reported physical function and global health status (EORTC QLQ-C30); investigator-assessed PFS rates at 6 months and 1 year; OS rates at 1 and 2 years; safety and PK. Clinical trial information: NCT04471428.
Characteristics of Patients with Type 1 Diabetes and Additional Autoimmune Disease in the DPV Registry
Authors: Prinz Nicole , Tittel Sascha R , Bachran Rainer , Birnbacher Robert , Brückel Joachim , Dunstheimer Désirée , Haberland Holger , Hess Melanie , Karges Wolfram , Oeverink Rudolf , Veigel Andreas , Holl Reinhard W
Published: June 2021

Context

Autoimmune diseases affect ~8% of the population. Type 1 diabetes mellitus (T1DM) is linked to other autoimmune diseases (AIDs), such as autoimmune thyroid disease or Addison’s disease (AD), that may impact diabetes therapy and outcome.

Objective

To analyze demographic and clinical characteristics of other AIDs in T1DM from a large standardized registry, the Prospective Diabetes Follow-up Registry (DPV).

Methods

We searched the registry for T1DM with the additional diagnosis of Hashimoto’s thyroiditis (HT), Graves’ disease (GD), and/or AD. T1DM with other AIDs (n = 6166, 5.4%) were compared with isolated T1DM (n = 107 457). For group comparisons, we used multivariable regression models with age, sex, diabetes duration, migration background, and type of insulin regimen as basic adjustments (microvascular endpoints: additionally adjusted for glycated hemoglobin).

Results

Patients with additional AIDs were more often female (54.7 vs 32.0%, P < .001) and had a longer diabetes duration (7.9 [4.2-12.5] vs 6.7 [2.7-12.9] years, P < .001). After adjustment, daily insulin dosage was higher in AD and HT than in isolated T1DM (0.858 ± 0.032 and 0.813 ± 0.005 vs 0.793 ± 0.001 IU/kg per day). Retinopathy was less common in HT (1.5%), whereas it was more frequent in GD (3.1%) than in isolated T1DM (1.8%). In both GD and HT, microalbuminuria occurred less often (10.6% and 14.3% vs 15.5%) and neuropathy (2.1% and 1.8% vs 0.8%) was more common than in isolated T1DM. All P < .05.

Conclusion

T1DM with additional AIDs show heterogeneous differences compared with isolated T1DM. T1DM plus AD or HT requires more insulin. Further, the rate of neuropathy is higher in HT or GD, whereas the rate of microalbuminuria is lower.
Space charge and lattice driven resonances at the CERN injectors
Authors: Ασβεστά Φωτεινή
Published: June 2021

Η παρούσα διδακτορική διατριβή εστιάζει στο φαινόμενο χωρικού φορτίου παρουσία βητατρονικών συντονισμών στους επιταχυντές του Ευρωπαϊκού Κέντρου Πυρηνικών Ερευνών (CERN) και πιο συγκεκριμένα στο σύγχροτρο πρωτονίων (PS) και στο σύγχροτρο πρωτονίων booster (PSB). Το φαινόμενο χωρικού φορτίου είναι το κυρίαρχο φαινόμενο για τη δυναμική σε επιταχυντές υψηλής λαμπρότητας και χαμηλής ενέργειας, όπως οι επιταχυντές που μελετήθηκαν. Αποτελεί τον κύριο περιορισμό για την αποδοτικότητά τους κατά την λειτουργία. Στον PS, απώλειες παρατηρούνται για βητατρονικές συχνότητες μεγαλύτερες από Qy=6.25, κυρίως για δέσμες με ισχυρό φαινόμενο χωρικού φορτίου. Η παρούσα εργασία δείχνει ότι αυτή η συμπεριφορά οφείλεται σε συντονισμούς που εγείρονται από το φαινόμενο χωρικού φορτίου εξαιτίας της υψηλής συμμετρικότητας του PS, τυπικό χαρακτηριστικό των συγχρότρων πρώτης γενιάς. Προσομοιώσεις αποδεικνύουν ότι ο συντονισμός που παρατηρείται όταν Qy=6.25 είναι μη συνεκτικός. Ο αναλυτικός υπολογισμός των όρων οδήγησης συντονισμού (RDT) που προέρχονται από το δυναμικό του φαινομένου χωρικού φορτίου καταδεικνύει ότι οι συχνότητες λειτουργίας του PS περιβάλλεται από πολλαπλούς μη συνεκτικούς συντονισμούς εξαιτίας του φαινομένου χωρικού φορτίου. Αντίστοιχα, μελέτες ανάλυσης και χαρτογράφησης του χώρου των συχνοτήτων (FMA) δείχνουν την οδήγηση των συντονισμών και αποκαλύπτουν ότι ο μηχανισμός που οδηγεί στις παρατηρούμενες απώλειες είναι η περιοδική διάσχιση των συντονισμών. Πειραματικές μελέτες και προσομοιώσεις δείχνουν την απόκριση των δεσμών υψηλής λαμπρότητας στην PS στους συντονισμούς καταγράφοντας τις απώλειες και την αύξηση της εκπεμπτικότητας. Η χρήση δεσμών μικρότερη λαμπρότητας επιτρέπει τον προσδιορισμό και την αντιστάθμιση συντονισμών που οφείλονται σε σφάλματα στον επιταχυντή. Τέλος, μετρήσεις και προσομοιώσεις σε συντονισμούς οφειλώμενους είτε σε σφάλματα είτε στο φαινόμενο χωρικού φορτίου καταδεικνύουν τη διαφορετική συμπεριφορά των απωλειών με βάση την λαμπρότητα της δέσμης και την πηγή της διέγερσής τους. Το τελευταίο μέρος της διατριβής παρουσιάζει μελέτες στον PSB, και συγκεκριμένα για τον συντονισμό Montague, συντονιμός εγειρόμενος από το φαινόμενο χωρικού φορτίου που προκαλεί σύζευξη των εγκάρσιων πεδίων της κίνησης. Η αναλυτική προσέγγιση του υπολογισμού των RDT φανερώνει ότι η μηχανή θα μπορούσε να λειτουργεί σε ένα διαφορετικό χώρο συχνοτήτων, Q4Q3, όπου ο συντονισμός καταστέλλεται. Μετρήσεις και προσομοιώσεις με διαφορετικές ταχύτητες διέλευσης του συντονισμού, φανερώνουν ανταλλαγή εκπεμπτικοτήτων στον σύνηθες χώρο λειτουργίας, Q4Q4, ενώ η καταστολή του συντονισμού στον χώρο Q4Q3 φανερώνεται με την διατήρηση της εκπεμπτικότητας και στα δύο εγκάρσια πεδία της κίνησης κατά τη διέλευση του συντονισμού. Ο συντονισμός Montague μελετήθηκε και σε συνδυασμό με γραμμικούς συντονισμούς που προκαλούν σύζευξη της κίνησης και εγείρονται από σφάλματα στον επιταχυντή σε μετρήσεις και προσομοιώσεις.
Antiphospholipid syndrome and pregnancy
Authors: Rahman Anisur
Published: June 2021

Professor Anisur Rahman explains why it is important for patients with antiphospholipid syndrome to be managed during pregnancy by multi-disciplinary teams, including obstetricians and midwives
Telehealth and maternity
Authors: Westwood Anjali Raj
Published: June 2021

Has the onset of the pandemic changed the way we utilise telemedicine forever? Anjali Raj Westwood shares her views
Weight loss and financial incentives: a flawed scheme?
Authors: Winter George
Published: June 2021

The use of financial incentives in healthcare is controversial. George Winter looks at the evidence behind these schemes
Application of State Transition Energy Management Control Algorithm in Fuel Cell
Authors: Pan Zheng , Xiao Qihong , Chen Yangliang
Published: June 2021

Dynamic programming algorithms are widely used in motor vehicle fuelcells, and can help battery energy management control to perform erroranalysis. The paper designs the decision-making process of fuel cell chargeand discharge management based on the state transition energy managementalgorithm, which is used to analyse the cumulative causes of errors andthe corresponding results. The article uses simulation software to simulatethe algorithm proposed in this paper, and finds that the algorithm is anenergy management optimization decision, and the error of the hydrogenconsumption obtained by the algorithm relative to the theoretical optimalhydrogen consumption is less than 0.25%.
Strategies for Implementing the Jakobsson-Floberg-Olsson Cavitation Model in EHL Simulations of Translational Seals
Authors: Bauer Niklas , Rambaks Andris , Müller Corinna , Murrenhoff Hubertus , Schmitz Katharina
Published: June 2021

The numerically stable simulation of cavitation effects is mandatory for predicting the friction and wear behavior of translational hydraulic seals. This contribution provides a comparison of two different implementations of the Jakobsson-Floberg-Olsson (JFO) cavitation model, an investigation of their properties and possible options for their stabilization. These methods are tested and compared both within a simple divergent gap test case as well as within an EHL simulation of a rubber metal contact. Based on these comparisons and theoretical investigations, the strengths and weaknesses of the different methods are summarized and discussed with respect to an application in EHL simulations of translational hydraulic seals.
Exploring Cybersecurity Ecosystem in the Middle East: Towards an SME Recommender System
Authors: Naveed Ahmed Nadir , Nanath Krishnadas
Published: June 2021

Cybersecurity is described as the protection of data resources by treating threats that jeopardize data. Enterprises must manage the cybersecurity risks so that the security and resilience of their assets may be improved. Cyber-attacks on Small and Medium Enterprises (SMEs) are rising. However, they often lack effective strategies to prevent threats such as malware, phishing, denial of service (DoS), and others. Their weak defense system is often an attractive avenue for hackers to explore loopholes. There is a lack of cybersecurity initiatives in SMEs, and several past attacks have exposed the weak systems. This paper first attempts to investigate the current scenario of cybersecurity in the context of Middle East SMEs. A survey of SMEs in the Middle East (cybersecurity space) helped understand the existing scenario, actual requirements, and challenges SMEs face. The research then explores the need for SMEs to choose the apt security solution to cater to their business needs. By reviewing the existing standards and pointers in different parts of the world, this research proposes a cybersecurity recommender system for SMEs in the Middle East. One of the survey findings reveals that most SMEs require adequate cybersecurity awareness, followed by evaluating the organization’s preventive capabilities. The dearth of information available online and the IT consultants’ conflicting guidance usually creates an information overload in deciding a neutral solution to address their needs. The recommender system attempts to structure the information available as a framework in deciding a cybersecurity solution for SMEs.
Flame analysis using a simple transmission digital holographic interferometer
Authors: De La Torre I. Manuel H. , Frausto-Reyes Claudio , Moreno-H. David , Salgado-Transito Ivan
Published: June 2021

A digital holographic interferometer using a collimated beam in transmission mode to illuminate a flow coming from a diffusion flame is presented. The optical system proposes an indirect visualization of the flow to avoid saturation at the sensor. It can detect the intensity signal as a classical schlieren technique and the phase changes due to the presence of the flow. It is possible to retrieve a pseudo-3D flow’s view and different gradient maps using the optical phase. According to the knife edge’s position, these gradients could be observed in classical schlieren one at a time, but the proposed system could retrieve them all with a single image hologram. As proof of principle, a flame’s flow is simultaneously observed with the optical system and a Z-type schlieren set up. A comparison of the visualized flows at different stages of the flame is presented and discussed. A temperature profile is obtained and validated with a thermocouple’s point thermal measurements taking the resulting optical phase. Results from both optical techniques show a good agreement.
Sensitivity enhancement of the SPR biosensor for Pseudomonas bacterial detection employing a silicon-barium titanate structure
Authors: Vasimalla Yesudasu , Pradhan Himansu Shekhar , Pandya Rahul Jasvantbhai
Published: June 2021

A novel, to the best of our knowledge, surface plasmon resonance (SPR) sensor, employing a silicon-barium titanate structure for Pseudomonas bacterial detection, is designed. Three bacterial attachments operate as a protective layer for the detection process with refractive indices (RI) of 1.437, 1.49368, and 1.5265. Performance analysis shows a sensitivity (

S

) of 155, 168, and 370°/RIU at RI of 1.5265 for Structures 1, 2, and 3, respectively. Additionally, the proposed sensor (Structure 3) accomplishes a magnified figure of merit (FOM) of 86.43 and quality factor of 86.65 at the RI of 1.5265. Finally, the proposed sensor’s performance is compared with that of the existing sensors, thus demonstrating a heightened

S

and FOM.
Longitudinal monitoring of tumor response to immune checkpoint inhibitors using noninvasive diffuse reflectance spectroscopy
Authors: Troncoso Joel Rodriguez , Diaz Paola Monterroso , Lee David E. , Quick Charles M. , Rajaram Narasimhan
Published: June 2021

Immune checkpoint inhibitors have revolutionized cancer treatment. However, there are currently no methods for noninvasively and nondestructively evaluating tumor response to immune checkpoint inhibitors. We used diffuse reflectance spectroscopy to monitor in vivo tumor microenvironmental changes in response to immune checkpoint inhibitors in a CT26 murine colorectal cancer model. Mice growing CT26 tumor xenografts were treated with either anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, or isotype control on 3 separate days. Monotherapy with either anti-PD-L1 or anti-CTLA-4 led to a large increase in tumor vascular oxygenation within the first 6 days. Reoxygenation in anti-CTLA-4-treated tumors was due to a combination of increased oxygenated hemoglobin and decreased deoxygenated hemoglobin, pointing to a possible change in tumor oxygen consumption following treatment. Within the anti-PD-L1-treated tumors, reoxygenation was primarily due to an increase in oxygenated hemoglobin with the minimal change in deoxygenated hemoglobin, indicative of a likely increase in tumor perfusion. The tumors in the combined treatment group did not show any significant changes in tumor oxygenation following therapy. These studies demonstrate the sensitivity of diffuse reflectance spectroscopy to tumor microenvironmental changes following immunotherapy and the potential of such non-invasive techniques to determine early tumor response to immune checkpoint inhibitors.
Instantaneous microwave-photonic spatial-spectral channelization via k-space imaging
Authors: Ryan Conor J. , Beardell William L. , Murakowski Janusz , Schneider Garrett J. , Prather Dennis W.
Published: June 2021

The ability to both spatially and spectrally demultiplex wireless transmitters enables communication networks with higher spectral and energy efficiency. In practice, demultiplexing requires sub-millisecond latency to map the dynamics of the user space in real-time. Here, we present a system architecture, referred to as k-space imaging, which channelizes the radio frequency signals both spatially and spectrally through optical beamforming, where the latency is limited only by the speed of light traversing the optical components of the receiver. In this architecture, a phased antenna array samples radio signals, which are then coupled into electro-optic modulators (EOM) that coherently up-convert these signals to the optical domain, preserving their relative phases. The received signals, now optical sidebands, are transmitted in optical fibers of varying path lengths, which act as true time delays that yield frequency-dependent optical phases. The output facets of the optical fibers form a two-dimensional optical phased array in an arrangement preserving the phases generated by the angle of arrival (AoA) and the time-delay phases. Directing the beams emanating from the fibers through an optical lens produces a two-dimensional Fourier transform of the optical field at the fiber array. Accordingly, the optical beam formed at the back focal plane of the lens is steered based upon the phases, providing the angle of arrival and instantaneous frequency measurement (IFM), with latency determined by the speed of light over the optical path length. We present a numerical evaluation and experimental demonstration of this passive AoA- and frequency-detection capability.
Dressmaking rediscovered: When design meets fashion in Helsinki
Authors: Chun Namkyu
Published: June 2021

Fashion design as a combined term conveys a different connotation than separate words of fashion and design. This is due to the complexity of the fashion system that also involves certain social prejudices, such as gendered practice and being shallow. This has set a gap for considering fashion design as a serious topic to study in comparison to other design subfields such as architecture and industrial design. However, this article argues that by emphasizing the dressmaking aspect in designing fashion, prejudices can be overcome. Finland, especially its capital Helsinki, is an established place for design and an emerging place for fashion. The recent development of the place where the encounter of design and fashion took place provides a unique condition for exploring the contemporary dressmaking practice of Helsinki-based fashion designers. A number of aspects identified from the context are shared to demonstrate how fashion design can be revisited besides the image-making aspect.
Adding Branched-Chain Amino Acids to an Enhanced Standard-of-Care Treatment Improves Muscle Mass of Cirrhotic Patients With Sarcopenia: A Placebo-Controlled Trial
Authors: Hernández-Conde Marta , Llop Elba , Gómez-Pimpollo Lucía , Fernández Carrillo Carlos , Rodríguez Luís , Van Den Brule Enrique , Perelló Christie , López-Gómez Marta , Abad Javier , Martínez-Porras José Luís , Fernández-Puga Natalia , Ferre Carlos , Trapero María , Fraga Enrique , Calleja José Luis
Published: June 2021

INTRODUCTION:

The effect of branched-chain amino acid (BCAA) supplementation on muscle mass in patients with cirrhosis and sarcopenia is unknown.

METHODS:

This is a pilot, prospective, randomized, and double-blind study of a cohort of 32 patients with cirrhosis and sarcopenia diagnosed by computed tomography scan who underwent a nutritional and physical activity intervention for 12 weeks. They were divided into 2 groups (placebo: 17 patients; BCAA: 15 patients). The study protocol was registered at ClinicalTrials.gov (NCT04073693).

RESULTS:

Baseline characteristics were similar in both groups. After treatment, only the BCAA group presented a significant improvement in muscle mass (43.7 vs 46 cm2/m2; P = 0.023). Seventeen patients (63%) presented improvement in muscle mass overall, which was more frequent in the BCAA group (83.3 vs 46.7%; P = 0.056). Regarding frailty, there was a significant improvement in the Liver Frailty Index in the global cohort (n = 32) after the 12 weeks (4.2 vs 3.9; P < 0.001). This difference was significant in both groups: in the placebo group (4.2 vs 3.8; P < 0.001) and in the BCAA group (4.2 vs 3.9; P < 0.001). After treatment, the BCAA group had a higher increase in zinc levels than the placebo group (Δzinc: 12.3 vs 5.5; P = 0.026). In addition, there was a trend for greater improvement of albumin levels in the BCAA group (Δalbumin: 0.19 vs 0.04; P = 0.091).

DISCUSSION:

BCAA supplementation improves muscle mass in cirrhotic patients with sarcopenia.
Vie et émotions des équipes entrepreneuriales étudiantes
Authors: Foliard Stéphane , Le Pontois Sandrine
Published: June 2021

Les programmes d’enseignement de l’entrepreneuriat font régulièrement appel au travail en équipe. Sur la durée, le niveau de motivation des étudiants est variable et des tensions apparaissent régulièrement. À partir d’une étude qualitative portant sur 13 équipes et 66 étudiants issus de deux écoles de commerce françaises, nous identifions 5 événements clés du processus entrepreneurial et les relions aux émotions positives et négatives qu’ils génèrent ainsi qu’à leur impact sur la motivation des membres de l’équipe et les stratégies de coping mobilisées. Notre contribution consiste à nommer ces émotions et à caractériser leur valence. Percevoir ces émotions et leurs effets permet d’identifier les équipes dysfonctionnelles ou d’entretenir les dynamiques positives par un accompagnement adapté.
Introduction d’une plateforme numérique dans un dispositif APP – quelles adaptations, quelle influence sur la coopération/collaboration étudiante ?
Authors: Hoffmann Christian , Girault Isabelle , Kahane Claudine , D'Ham Cédric , Planche Maëlle
Published: June 2021

Nous présentons dans cet article une analyse des gains constatés et des difficultés rencontrées lors de l’introduction d’une plateforme numérique dans un dispositif d’apprentissage sous forme d’Apprentissage Par Problèmes (APP). L’étude croise le bilan des enseignants, des retours d’étudiants et des traces d’activité enregistrées sur la plateforme. Une attention particulière est portée à l’influence de la plateforme sur la coopération/collaboration entre étudiants.
Management of the State and Development of Human Resources of Industrial Enterprise in Accordance with the Dynamics of the Influence External and Internal Fac-tors
Authors:   South Ural State University, Korennaya K.A. , Loginovskiy O.V. , Zakharov V.V.
Published: June 2021

The specifics of human resource management primarily consider the work with the personnel of enterprises and organizations, and the basic concept that existed earlier said that the human resource and personnel of enterprises and organizations are some expenses that need to be constantly repaid. Now, personnel-human resources are considered as the resources of the enterprise, and this approach is used to increase the understanding of the belonging of employees and more effective use of their competencies in the organization system. Respectively, as resources are one of the most important characteristics of the enterprise and personnel should be attributed to the resources necessary for the sustainable development and functioning of the enterprise. The general concept of human resource management provides for a set of certain beliefs and suggestions that are formed and focused in one company, so you can talk about the corporate culture, about specific factors that are accepted in the company, and are, in turn, also a certain resource. The aim of the study is to form an up-to-date approach to improving the efficiency of human resource management at an industrial enterprise. Materials and methods. As part of the materials and methods, it is necessary to note the analysis of approaches, methods and models of human resource management presented in the scientific and technical literature, as well as the results of their implementation in the practice of industrial enterprise management. Results. The article substantiates the main scientific provisions and the need to form a general strategy for personnel development, which forms employees' self-determination in the organizational structure of the enterprise and the vector of their development, and the management has a clear idea in the development of personnel management decisions. Conclusion. A vague formulation, the absence of a personnel development strategy or its inconsistency with the general strategy of the enterprise and the dynamics of the influence of external and internal factors creates some uncertainty, which further leads to the “turnover” of personnel and does not allow achieving the goals set by the management of the enterprise.