bluuebunny/crossref_metadata_2025 huggingface dataset:
3D-printing inherently MRI-visible accessories in aiding MRI-guided biopsies
Authors: Wang Yanlu
Published: August 2024

Background

3D printers have gained prominence in rapid prototyping and viable in creating dimensionally accurate objects that are both safe within a Magnetic Resonance Imaging (MRI) environment and visible in MRI scans. A challenge when making MRI-visible objects using 3D printing is that hard plastics are invisible in standard MRI scans, while fluids are not. So typically, a hollow object will be printed and filled with a liquid that will be visible in MRI scans. This poses an engineering challenge however since objects created using traditional Fused Deposition Modeling (FDM) 3D-printing techniques are prone to leakage. Digital Light Processing (DLP) is a relatively modern and affordable 3D-printing technique using UV-hardened resin, capable of creating objects that are inherently liquid-tight. When printing hollow parts using DLP printers, one typically requires adding drainage holes for uncured liquid resin to escape during the printing process. If this is not done liquid resin will remain inside the object, which in our application is the desired outcome.

Purpose

We devised a method to produce an inherently MRI-visible accessory using DLP technology with low dimensional tolerance to facilitate MRI-guided breast biopsies.

Methods

By hollowing out the object without adding drainage holes and tuning printing parameters such as z-lift distance to retain as much uncured liquid resin inside as possible through surface tension, objects that are inherently visible in MRI scans can be created without further post-processing treatment.

Results

Objects created through our method are simple and inexpensive to recreate, have minimal manufacturing steps, and are shown to be dimensionally exact and inherently MRI visible to be directly used in various applications without further treatment.

Conclusion

Our proposed method of manufacturing objects that are inherently both MRI safe, and MRI visible. The proposed process is simple and does not require additional materials and tools beyond a DLP 3D-printer. With only an inexpensive DLP 3D-printer kit and basic cleaning and sanitation materials found in the hospital, we have demonstrated the viability of our process by successfully creating an object containing fine structures with low spatial tolerances used for MRI-guided breast biopsies.
Morphological and cytological assessments reveal pollen degradation causes pollen abortion in cotton cytoplasmic male sterility lines
Authors: Pei Qingyu , Liu Jinshan , Guo Chunping , Ma Xiaomei , Liu Xiaoyan , You Chunyuan , Lin Hairong , Li Zhibo , Zhao Ruihai , Zhu Bo , Wu Yuanlong , Pan Zhenyuan , Nie Xinhui
Published: August 2024

Background

Understanding the mechanism of male sterility is crucial for producing hybrid seeds and developing sterile germplasm resources. However, only a few cytoplasmic male sterility (CMS) lines of cotton have been produced due to several challenges, like inadequate variation of agronomic traits, incomplete sterility, weak resilience of restorer lines, and difficulty in combining strong dominance. Therefore, the morphological and cytological identification of CMS in cotton will facilitate hybrid breeding.

Results

Two F2 segregating populations of cotton were constructed from cytoplasmic male sterile lines (HaA and 01A, maternal) and restorer lines (HaR and 26R, paternal). Genetic analysis of these populations revealed a segregation ratio of 3:1 for fertile to sterile plants. Phenotypic analysis indicated no significant differences in traits of flower bud development between sterile and fertile plants. However, sterile plants exhibited smaller floral organs, shortened filament lengths, and anther atrophy on the flowering day in comparison with the fertile plants. When performed scanning electron microscopy (SEM), the two F2 populations revealed morphological variations in the anther epidermis. Cellular analysis showed no significant differences in pollen development before pollen maturation. Interestingly, between the pollen maturation and flowering stages, the tapetum layer of sterile plants degenerated prematurely, resulting in abnormal pollen grains and gradual pollen degradation.

Conclusion

The results of this study suggest that fertility-restoring genes are controlled by a single dominant gene. Sterile plants exhibit distinctive floral morphology, which is characterized by stamen atrophy and abnormal anthers. Pollen abortion occurs between pollen maturity and flowering, indicating that premature tapetum degradation may be the primary cause of pollen abortion. Overall, our study provides a theoretical basis for utilizing CMS in hybrid breeding and in-depth investigation of the dominant configuration of cotton hybrid combinations, mechanisms of sterility, and the role of sterile and restorer genes.
Nutritional compositions, microbial quality, bioactivities, and volatile compounds of a novel vinegar from wild edible mushroom, Russula delica Fr
Authors: Saithong Pramuan , Permpool Jirawut , Rattanaloeadnusorn Sukhan , Poompurk Pholsit , Khunnamwong Pannida , Lomthong Thanasak
Published: August 2024

Vinegar is commonly utilized in cooking and food preparation as a flavoring, preservative, and condiment. It can be made from various sources, including fruits, grains, and vegetables. This study produced vinegar from a wild edible mushroom, Russula delica Fr., using microwave-assisted enzymatic hydrolysis extraction. The nutritional composition, bioactivities, microbial quality, and volatile compounds were analyzed in the production process and final vinegar product. Sugar syrup as total soluble solids (TSS) and total phenolic content (TPC) were extracted from mushroom powder using commercial enzymes and yielded 5.60 ± 0.10°Brix and 7.01 ± 0.06 mg GAE/g substrate, respectively. The extracted syrup was rich in amino acids such as aspartic and glutamic acid, with glucose as the main type of sugar. Maximum alcohol content at 10.95 ± 0.21% (w/v) with 1.28 ± 0.23 mg GAE/mL TPC was obtained from Saccharomyces cerevisiae fermentation after 21 days, while highest acetic acid was obtained at 5.60 ± 0.42% w/v with 1.87 ± 0.14 mg GAE/mL of TPC content and 74.85 ± 1.24% of DPPH radical scavenging activity after surface fermentation using Acetobacter aceti TISTR 354. Thirteen volatile compounds, including acids, alcohols, and aldehydes, were found in the wild edible mushroom vinegar, contributing to the unique aroma of the product. This study presented the first report on the analysis of vinegar from a wild edible mushroom, R. delica Fr. which showed high nutritional value, antioxidant activity and volatile compounds, with the potential for future commercial production.

Graphical Abstract
Does the management of patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) changes with advanced diagnostic workup beyond coronary angiography? Results from the “Evaluation of the clinical Profile, Investigations and Cardiac Imaging of the Patients with MINOCA (EPIC-MINOCA Study)”
Authors: Chander Yogesh , Duggal Bhanu , Soni Shishir
Published: August 2024

Background

Evaluation of the patients with MINOCA and identifying the underlying aetiology remains challenging. However, investigation in most patients remains limited to coronary angiography (CAG). The study aimed to assess the clinical profile, investigations and cardiac imaging of the patients with MINOCA and its outcomes.

Results

Out of 55 patients with MINOCA, CAG was normal in 16 (29.1%), while 39 (69.9%) had nonobstructive coronary artery disease. Of 55 patients, 34 had limited workup (Group 1) and only 21 had advanced workup (Group 2). In comparison to Group 1, Group 2 had a significantly higher association with the identification of possible underlying aetiology (16 vs. 4, p < 0.001) and a change in the management (10 vs. 3, p = 0.002).

Conclusion

Diagnostic workup in patients with MINOCA was limited to CAG in 61.8% of patients in this study. However, patients with advanced workup had a significantly higher association with the change in the treatment and identifying possible underlying aetiology in such patients.
The significance of artificial intelligence in zero trust technologies: a comprehensive review
Authors: Ajish Deepa
Published: August 2024

In the era of cloud computing, cybersecurity has assumed paramount importance. As organizations transition to cloud-based solutions, cyberattackers increasingly target cloud services as a lucrative avenue for unauthorized access to sensitive information. The traditional security perimeter, once robust, now exhibits porosity, necessitating a reevaluation of security strategies to counter these evolving threats. This paper delves into the critical role of artificial intelligence (AI) within zero trust security technologies. The convergence of AI and zero trust has garnered significant attention, particularly in the domains of security enhancement, risk mitigation, and the redefinition of trust paradigms. My exploration aims to uncover how AI actively observes and supports various technologies in zero trust model. By evaluating existing research findings, I illuminate the transformative potential of AI in fortifying security within zero trust security models. This scholarly perspective underscores the critical interplay between AI and zero trust technologies, highlighting their collective potential in safeguarding digital ecosystems.
Executive functions in mid-life adults with mild sensorineural hearing loss compared with age-matched controls with normal hearing
Authors: Chandrashekar Pooja , Nagaraj Hema
Published: August 2024

Purpose

This study explores the relationship between sensorineural hearing loss (SNHL) in mid-life adults and cognitive function, focusing on executive functions. Given the projected rise in dementia cases, identifying modifiable risk factors for cognitive decline is imperative. SNHL has emerged as a potential risk factor, with hearing loss accounting for a substantial portion of dementia cases. However, the cognitive implications of SNHL in mid-life adults are not well understood.

Method

The study examined 50 participants, 25 with bilateral unaided mild SNHL (AHL) and 25 with normal hearing (ANH). A battery of audiological assessments and cognitive tests, including the Trail Making Test (TMT), was administered. TMT measures included direct scores (completion time and errors) and derived scores (difference, ratio, proportion, sum, and multiplication scores).

Results

The AHL group displayed significantly poorer peripheral hearing compared to the ANH group, as reflected in pure-tone audiometry, speech reception thresholds, and speech identification scores. Significant differences were observed in all direct and derived TMT measures except for the ratio and proportion scores. This suggests that while overall cognitive disturbances were evident in the AHL group, they were not exclusive to executive function deficits. Notably, we did not identify any statistically significant effects of hypertension, diabetes, smoking, alcohol consumption, or physical activity on TMT scores.

Conclusion

This study highlights the potential impact of SNHL on cognitive function in mid-life adults. Mid-life SNHL is associated with cognitive differences, emphasizing its role as a modifiable risk factor for future cognitive decline. This research underlines the need for further investigation into the cognitive effects of aided hearing and a multidisciplinary approach to understanding these alterations in cognitive function.
Initial results from phase I trial of a novel oncolytic adenovirus Ad-TD-nsIL12 in recurrent glioblastoma connecting to ventricular system.
Authors: Qian Xiao , Ning Weihai , Guo Yuduo , Li Shenglun , Song Dixiang , Liu Deshan , Ma Lixin , Chen Yujia , Zhao Chao , Xu Jiacheng , Qu Yanming , Wang Haoran , Gu Chunyu , Zhang Mingshan , Wang Yaohe , Dunmall Louisa Chard , Wang Shengdian , Zhang Hongwei
Published: August 2024

2057

Background: Glioma is the most common primary central nervous system malignancy in adults, of which glioblastoma (GBM) accounts for more than 50% of the incidence and is the most aggressive subtype of glioma, with a median survival of about 15 months. Oncolytic virus emerges as a promising therapy for recurrent GBM (rGBM), but its safety and efficacy are not evaluated in patients with rGBM connecting to ventricular system. Methods: This is a dose-escalating trial to study the safety and efficacy of Ad-TD-nsIL12, a novel oncolytic adenovirus, in patients with rGBM connecting to the ventricular system. The assigned dose levels of Ad-TD-nsIL12 were 5x109vp, 1x1010vp, and 5x1010vp. Adverse events (AEs) associated with the virus were graded using the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), and Grade ≥ 3 AEs identified the dose-limiting toxicity (DLT). Tumor response was evaluated based on the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Eight patients, aged from 45 to 71 years, were enrolled between December 2019 and September 2022, with treatment doses ranging from 5x109 to 5x1010vp. Grade 3 seizure according to CTCAE occurred in two patients from Cohort 3 (5x1010vp) after AD-TD-nsIL12 injection. Minimal adverse events were observed at a treatment dose of 1x1010 vp, even after multiple injections. Complete response (CR) was demonstrated in one patient, partial response (PR) in one patient, stable disease (SD) in four patients and progressive disease (PD) in two patients. Immunohistochemical staining showed higher infiltrations of CD3+, CD4+ and CD8+ T cells and positivity of E1A and Hexon in virus post-treated tissues. Inflammation associated cytokines in the blood were not significantly elevated by Ad-TD-nsIL12. Conclusions: AD-TD-nsIL12 treatment was safe and effective in patients with rGBM and warrants examination in a phase II clinical study. Clinical trial information: ChiCTR2000032402.
Results of a phase 1/2 study of MHB088C: A novel B7H3 antibody-drug conjugate (ADC) incorporating a potent DNA topoisomerase I inhibitor in recurrent or metastatic solid tumors.
Authors: Shen Lin , Zhou Caicun , Meng Xue , Sun Yuping , Ji Yinghua , Yang Haihua , Ning Fangling , Han Liang , Jiang Ou , Sun Meili , Wen Qing , Yu Xinmin , Jia Yuming , Huang Hai , Zhao Yanqiu , Zhang Zhiye , Tian Chuntao , Zhang Zhen , Shi Junwei , Cao Guoqing
Published: August 2024

3012

Background: MHB088C is an investigational B7H3-directed ADC, created by coupling a humanized anti-B7H3 monoclonal antibody with a highly potent DNA topoisomerase I inhibitor (5~10 times more potent than DXd). Preclinical studies demonstrated robust binding affinity, superior internalization rates, powerful tumor killing activities (3~10 times more potent than the DS-7300a analog in CDX models) and a favorable safety profile with no unique toxicities observed in the GLP study as compared to other B7H3 ADCs and no occurrences of interstitial lung disease (ILD). We here present the safety and efficacy results from a first-in-human phase 1/2 study of MHB088C. Methods: The study enrolled patients (pts) with recurrent or metastatic solid tumor across two segments: dose-escalation (D-esc) and dose-expansion (D-exp). In the D-esc phase, MHB088C was administrated intravenously at doses of 0.8, 1.6, 3.0mg/kg Q2W; 3.0, 4.0 mg/kg Q3W. Results: As of the data cutoff on Dec 31, 2023, 60 pts were enrolled and received at least one dose of MHB088C (D-esc, n=14; D-exp, n=46). 55 pts remain on the treatment and 12 pts had at least one tumor assessment according to RECIST 1.1. Dose-limiting toxicities (DLTs) were platelet count decreased and febrile neutropenia at 4.0 mg/kg Q3W. The MTD was determined to be 3.0 mg/kg Q3W. The most common TRAEs overall in ≥25% of pts were neutrophil count decreased, lymphocyte count decreased, and white blood cell (WBC) count decreased. The most common Grade ≥3 TRAEs (≥5% of pts) were neutrophil count decreased (33.3%), lymphocyte count decreased (30.0%), WBC count decreased (26.7%), platelet count decreased (23.3%), and anemia (15.0%). No ILD was reported. Of12 response-evaluable pts, 5 partial responses (PRs) were observed (ORR: 41.7%). The disease control rate was 91.7% (11/12). In the subset of 3 SCLC pts, all 3 showed PRs (ORR: 100.0%), with one case demonstrating complete response of the target lesion and another with close to 80% tumor volume reduction. The efficacy of 2 SCLC pts was achieved in 1.6 mg/kg Q2W group without major hematologic side effects. All responses among SCLC pts occurred at the first tumor assessment. Conclusions: MHB088C exhibited a manageable safety profile, with striking efficacy in SCLC pts. The dose optimization and expansion study is continuing to establish the RP2D for MHB088C. Clinical trial information: CTR20231298.
A phase Ib/IIa study of DX1002, a novel drug in patients with pretreated advanced hepatocellular carcinoma: Efficacy and safety analysis.
Authors: Yuan Min , Liu Zhuqing , Guo Xianling , Xu Qing
Published: August 2024

3122

Background: Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. DX1002 is a novel, specific, small-molecule, tubulin inhibitors, that targets the beta subunit of tubulin in tumor vascular endothelial cells. It has been designed to destroy tumor blood vessels which has been demonstrated in preclinical efficacy models. The objectives of this trial were to assess safety, tolerability and preliminary efficacy of DX1002 in patients (pts) with pre-treated advanced HCC or gastric cancer. Here, we present the results from the HCC subpart. Methods: This is a prospective, single-arm open-label multi-center phase Ib/IIa trial (CTR2400080296) to investigate DX1002 in patients with pre-treated advanced HCC or gastric cancer. Patients received DX1002 600 mg orally once daily, continuously in 28-day cycles until progressive disease or intolerable toxicity. Primary endpoints were safety and objective response rate (ORR); other endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), pharmacokinetics and safety. Results: From Jun-2021 to Jan-2024, 40 patients with advanced HCC were enrolled. The median age was 54 (36-71) years. As of 31-Jan-2024, of the 40 pts, 4 pts (10.0%) showed PR and 15 (37.5%) had SD. ORR was 21.1% and DCR was 47.5%. The median PFS was 3.55 (95% CI 2.89-8.31) months and median OS was 13.4 (95% CI 11.0-NA) months. Any-grade TRAEs occurred in 75% pts (30/40), with 22.5% Grade 3 (9/40). The most common TRAEs were Aspartate aminotransferase increased (22.5%), total bilirubin increased (20%), albuminuria (20%), Hypoalbuminemia (15%) and gamma-glutamyl transferase increased (15%). Four patients (10%) discontinued DX1002 due to TRAEs. No death-related cases occurred. Conclusions: Initial data shows DX1002 demonstrated manageable safety profile and promising anti-tumor potential in pre-treated advanced hepatocellular carcinoma. Further exploration of DX1002 in HCC is warranted. Clinical trial information: ChiCTR2400080296.
Perioperative PD-1 antibody tislelizumab plus chemotherapy for locally advanced gastro-oesophageal junction cancer: A prospective, nonrandomized, open-label, phase II trial.
Authors: Nie Run-Cong , Ding Ya , Yuan Shu-Qiang , Li Yuan-fang , Wang Wei , Chen Yongming , Cai Muyan , Sun Xiao-wei , Weng Desheng , Li Dandan , Zhao Jingjing , Chen Xiaojiang , Guan Yuanxiang , Ma Luo , Qiu Haibo , Zhou Zhi-wei , Zhang Xiao-Shi , Chen Ying-bo
Published: August 2024

4083

Background: The combination of PD-1 antibody and chemotherapy was shown to be effective in advanced gastric cancer, but has not yet been comprehensively investigated in locally advanced patients, especially in the context of adenocarcinoma of gastro-oesophageal junction (GEJ). In this study, we conducted a prospective, nonrandomized, open-label phase II trial to evaluate the effectiveness of adding PD-1 antibody to perioperative chemotherapy in patients with locally advanced resectable GEJ cancer. Methods: In this nonrandomized, open-label, phase II study, patients with resectable GEJ adenocarcinoma clinically staged as cT3-4aNanyM0 or cT1-2N+M0 were allocated three preoperative and five postoperative 3-week cycles of PD-1 antibody tislelizumab plus SOX (S-1 and oxaliplatin) regimen. The primary endpoint was major pathological response (MPR) rate. The secondary endpoints were pathological complete response (pCR), pathological complete /moderate regression rate (TRG 0/1), R0 resection rate, recurrence-free survival, event-free survival, overall survival, treatment safety and quality of life. The trial is registered at Chinese Clinical Trial Registry, identifier: ChiCTR2200058732. Results: Between Oct 2022 and June 2023, 32 patients were enrolled and assessed using intention-to-treat analysis. The median age was 60 years (range: 28-74 years), and 53.1% (17/32) patients were Siewert III type. All patients received at least one cycle of assigned preoperative treatment, and 96.9% (31/32) patients completed three cycles of assigned preoperative tislelizumab and SOX. R0 resection rate was 96.9% (31/32). The MPR rate was 37.5% (12/32, 95% CI: 21.1%-56.3%) and the pCR rate was 28.1% (9/32, 95% CI: 13.7%-46.7%). The surgical morbidity was 12.5% (4/32), and no 30-day mortality was observed. In the preoperative and postoperative treatment period, treatment-related grade 3-4 adverse events was 9.4% (3/32). At the date of 6th Feb 2024, three (9.4%) patients occurred recurrence. Conclusions: This is the first prospective study that focus on the perioperative immunotherapy in patients with resectable GEJ adenocarcinoma. Perioperative PD-1 antibody tislelizumab plus chemotherapy demonstrated a significantly improved pathological regression and might be a promising option for patients with locally advanced resectable GEJ adenocarcinoma. Clinical trial information: ChiCTR2200058732.
Preliminary results of phase I/II study to evaluate safety and efficacy of combination pucotenlimab with epidermal growth factor receptor-ADC (EGFR-ADC) MRG003 in patients with EGFR positive solid tumors.
Authors: Ruan Dan-yun , Han Fei , Zhou Yujuan , Wang Fenghua , Tang Lin-Quan , Li Zhiming , Chen Qiu-Yan , Chen Chunyan , Lin Jinguan , Liu Fu-Rong , Xiao Feng , Shi Yingrui , Xu Rui-Hua
Published: August 2024

6013

Background: Pucotenlimab (HX008) is a recombinant humanized PD-1 inhibitor approved for marketing in China, and MRG003 is an EGFR-ADC which has shown promising anti-tumor activity in squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal carcinoma (NPC) in multiple clinical studies. In the preclinical studies, the combination of them has demonstrated a synergistic antitumor effect. This study was aimed to assess the safety and efficacy of the combination therapy in patients (pts) with locally advanced or metastatic solid tumors known to express EGFR. Methods: In this Phase I/II dose escalation and expansion study, eligible pts were treated with 3.0 mg/kg HX008 combined with MRG003 every 3 weeks, with an escalated dosing ranging from 1.5 mg/kg to 2.3 mg/kg. The primary endpoints were maximum tolerated dose (MTD), recommended Phase II dose (RP2D) of combination and objective response rate (ORR). Secondary endpoints included duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS). Results: As of 30 January 2024 (cut-off date), 33 pts (9 NPC, 1 SCCHN and 3 other solid tumors pts in Phase I, 14 NPC and 6 SCCHN pts in Phase II) were enrolled in this study with a median age of 52 (31,65), and 25 pts (76%) were male. 11 (33%) pts were ECOG PS 0. The most commonly reported treatment-related adverse events (TRAEs) included pruritus (46%), rash (33%), AST increased (30%), anemia (30%). Grade 3-4 TRAEs occurred in 4 pts (12%), and mainly was white blood cell count decreased (9%) and hypokalemia (6%). The only DLT event occurred in the 2.3mg/kg dose group, and the RP2D of MRG003 determined was 2.0mg/kg by SMC. Out of the 27 evaluable pts, 17 pts achieved PR and 7 pts achieved SD, thus the ORR and DCR were 63.0% (95%CI: 42.4, 80.6) and 88.9% (95%CI: 70.8, 97.7), respectively. In the Phase II, among 9 evaluable EGFR-positive NPC pts progression after first-line treatment of PD-1 plus platinum-based chemotherapy, 2 CR, 5 PR and 2 SD were observed, ORR and DCR were 77.8% (95%CI:40.0, 97.2) and 100% (95%CI:66.4, 100), respectively. Five evaluable systemic treatment naïve SCCHN pts with EGFR-positive, 3 PR and 1 SD were observed, ORR and DCR were 60% (95%CI:14.7, 94.7) and 80% (95%CI:28.4, 99.5), respectively. The DOR and PFS in the study were immature. The longest patient treated has had a DOR for more than 17 months and still ongoing. Conclusions: The Phase I/II study pts treated with HX008 in combination with MRG003 demonstrated good tolerability and encouraging antitumor activity in NPC and SCCHN, especially in PD-1 treatment failed NPC pts. The Phase II study is currently ongoing. Research Sponsor: Shanghai Miracogen Inc. Clinical trial information: NCT05688605.
Neoadjuvant tislelizumab plus chemotherapy followed by salvage surgery and adjuvant tislelizumab for recurrent head and neck squamous cell carcinoma after radiotherapy: A single-arm, phase II trial.
Authors: Wu Wenjie , Wang Lin , Zhang Tong , Zhang Jie
Published: August 2024

6070

Background: Locoregional recurrence remains a significant challenge in head and neck squamous cell carcinoma (HNSCC) after surgery and radiotherapy. Salvage surgery is the best option if negative margins can be achieved, and this can be strengthened in the era of immunotherapy. However, some relevant questions remain unanswered. The objectives of this prospective study were to evaluate the efficacy and safety of neoadjuvant tislelizumab plus chemotherapy followed by salvage surgery and adjuvant tislelizumab for recurrent HNSCC after radiotherapy. Methods: In this phase II, single-arm study, eligible pts 18 years of age or older with locoregional recurrent HNSCC after radiotherapy received neoadjuvant therapy with tislelizumab (200 mg), albumin-bound paclitaxel (260 mg/m2), and cisplatin (60-75 mg/m2) Q3W for 2 cycles, followed by salvage surgery and adjuvant tislelizumab (200 mg) Q3W for 6 cycles. The primary endpoint was major pathologic response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS) and safety. Results: Between March 2022 and September 2023, 34 pts were enrolled. Median age was 56 (30-75) yrs, 20.6% smoking history, 20.6% alcohol history and 61.8% male. All pts completed neoadjuvant therapy with an ORR of 35.3% (12/34) and DCR of 94.1% (32/34). Twenty-six pts (23 OSCC, 3 OPSCC) successfully underwent surgery with MPR rate 19.2% (5/26), of which the pCR rate was 15.4% (4/26). At median follow-up of 15.1 months, 1-year EFS was 63.4% and 1-year OS was 82.5% for per-protocol population. Twenty-five pts complained symptoms included pain, trismus, dysphagic, and speech disorders at baseline visit, and 84% (21/25) achieved remission after 2 cycles of neoadjuvant therapy. Grade 1-2 adverse events (AEs) with an incidence greater than 10% include 94.1% alopecia, 38.2% fatigue, 35.3% anorexia, 17.6% hypothyroidism and 14.7% anemia. Grade 3-4 adverse events (AEs) occurred in 1 pts (2.9%) with G3 hyperglycemia. Conclusions: Neoadjuvant and adjuvant tislelizumab with salvage surgery is well tolerated. The 1-year EFS and OS compared favorably with historical data. These encouraging results warrant further investigations. Clinical trial information: ChiCTR2100054296.
An open-label randomized trial comparing addition of olanzapine 5 mg versus olanzapine 10 mg as anti-emetic to standard anti-emetic regime for doxorubicin or epirubicin and cyclophosphamide in breast cancer.
Authors: Tvsvgk Tilak , Thinley Dorji
Published: August 2024

e12531

Background: Chemotherapy-induced nausea and vomiting (CINV) is an important therapy related side effects in the treatment of malignancies. Breast cancer patients receive a highly-emetogenic chemotherapy with Doxorubicin or Epirubicin and Cyclophosphamide. The addition of Olanzapine 10 mg is known to reduce acute and delayed CINV, however, Olanzapine 10 mg is associated with somnolence and fatigue. In this study, the proportion of complete response of CINV to Olanzapine 5 mg was compared to Olanzapine 10 mg that was added to standard antiemetic regime. Methods: This was an open-label randomized clinical trial comparing the effectiveness of Olanzapine 5 mg against Olanzapine 10 mg in preventing acute and delayed phases of CINV. This study was conducted at a tertiary care cancer centre in India between 2020 – 2021. The sample size was calculated 118 subjects that were allocated with simple randomization method. The primary outcome of CINV in acute and delayed phase were collected using the Multinational Association for Supportive Care in Cancer (MASCC) Antiemesis Tool; the intensity of symptoms of nausea, retching and vomiting were assessed using the Rhodes index; the overall patient experience was assessed using the Edmonton Symptom Assessment Scale. The comparison of proportions of CINV in the two groups were compared using Chi-square test while intensity scores were compared using Wilcoxon rank-sum test. All p values <0.05 were considered significant. Ethics approval was obtained from the Institutional Review Board. The trial was registered at the Clinical Trials Registry of India. Results: Of the118 patients randomized, 57 received Olanzapine 5 mg and 61 received Olanzapine 10 mg in addition to standard antiemetic regime. The overall complete response rate was 54.2% in acute phase and 72.0% in delayed phase. The complete response rate of Olanzapine 5 mg was 57.9% in acute phase and 91.2% in delayed phase. The complete response rate of Olanzapine 10 mg was 50.9% in acute phase and 54.1% in delayed phase. The nausea intensity score on day 5 after chemotherapy was significantly lower among those receiving Olanzapine 10 mg. However, there were no difference in the reduction retching and overall symptoms between the groups. In terms of side effect profile, those receiving Olanzapine 10 mg reported significantly higher grades of somnolence and fatigue. There was no difference in the occurrence of pain, depression, anxiety, shortness of beath, appetite and wellbeing. Conclusions: There was no difference in the effectiveness of Olanzapine 5 mg compared to Olanzapine 10 mg in the prevention of CINV. However, Olanzapine 10 mg was associated with higher proportions of somnolence and fatigue. Therefore, it is recommended that Olanzapine 5 mg may replace current antiemetic regimes that contain Olanzapine 10 mg. Clinical trial information: CTRI/2020/01/023076.
Neoadjuvant anlotinib combined with penpulimab for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Updated data from a prospective, phase II trial.
Authors: Chen Yueyun , Yuan Yong , Yang Yu-Shang , Lin Zhen , Tian Jiangfang , Liu Ting , Yue Zheng , Shi Hua-Shan , Hu Yang , Ding Zhen-Yu
Published: August 2024

e16079

Background: Neoadjuvant chemoradiation therapy followed by radical surgery has been extensively recommended for locally advanced esophageal squamous cell carcinoma (ESCC). However, toxicities and challenges to the subsequent surgery limit its wide clinical application. Immune checkpoint inhibitors combined with antiangiogenesis have synergistic effects and have shown good therapeutic effects in previous studies, as well as fewer side effects. Here, we tested a novel combination of anlotinib (an antiangiogeneic kinase inhibitor) and penpulimab (an anti-PD-1 antibody), devoid of radio- or chemo-therapy, for the neoadjuvant therapy of locally advanced ESCC. Methods: In this prospective, single-arm, phase II clinical trial (ChiCTR2200064848), patients(pts) with resectable locally advanced ESCC (clinical stage III-IVa) were recruited. The study was designed using a two-stage minimax approach. The planned sample size was 40 pts would provide 80% power at a one-sided alpha error of 5%, threshold pathological complete response (pCR) of 16% and expected pCR of 30%. Pts received neoadjuvant therapy with anlotinib (8 mg, po, D1-14, Q3W) combined with penpulimab (200 mg, ivgtt, Q3W) for 2 cycles. Six to eight weeks later, pts underwent radical surgery after exclusion of contraindications. The primary endpoint was pCR rate. Secondary endpoints included tumor regression grade (TRG), R0 resection rate, objective response rate (ORR) and safety profile. Results: From Jan 2023 to Nov 2023, 25 pts (19 males and 6 females) were enrolled with a median age of 67 years (range: 50-74). A concerning 92% were diagnosed with lymph node metastasis. Moreover, 85% (22/25) pts exhibited medical contraindications, including pure red cell aplasia, compromised pulmonary function, and poor nutritional status, etc.) rendering them ineligible for standard neoadjuvant chemoradiotherapy or chemotherapy. All pts were available for efficacy assessment, ORR and DCR were 48.0% and 96.0%, respectively. Of these, 21 pts underwent esophagectomy, with an R0 resection rate of 90.5% (19/21). The study's initial phase successfully achieved its primary endpoint, with a pCR rate of 19.0% (4/21). Furthermore, the major pathological response (MPR) was 28.6% (6/21). The most common TRAEs (≥10%) included hypertension (28.0%), hand-foot syndrome (20%), fatigue (20%), abdominal pain (12%), toothache (12%). Grade 3-4 TRAEs were observed in 12.0% of the patients (3/25), and no reports of grade 5 TRAEs. Conclusions: Preliminary results from the initial stage suggest that anlotinib combined with penpulimab as a neoadjuvant treatment for ESCC showed promising safety and efficacy, especially for those deemed unsuitable for neoadjuvant chemoradiation or chemotherapy. More ESCC pts would be recruited in the future. Clinical trial information: ChiCTR2200064848.
Camrelizumab combined with chemotherapy followed by maintenance camrelizumab and apatinib as first-line therapy for extensive-stage small cell lung cancer: A phase II, single-arm, exploratory study.
Authors: Zhao Yanbin , Zhang Minghui , Liu Jinglei , Pu Haihong , Li Yinghong , Li Xin , Wang Yan
Published: August 2024

e20107

Background: Extensive-stage small-cell lung cancer (ES-SCLC), a type of aggressive tumor known as with limited therapeutic options and poor prognosis in the past decades, had recently been proved curatively effective by the combination of immune checkpoint inhibitor and platinum-based chemotherapy. Nonetheless, it is still worthy and necessary to explore the new treatment pattern considering the rapid disease progression feature of ES-SCLC. Whereupon, this study aims to explore the effectiveness and safety of camrelizumab combined with chemotherapy followed by maintenance camrelizumab and apatinib in the first-line treatment of ES-SCLC. Methods: In this phase II study, 40 patients with pathological diagnosis of ES-SCLC and without receiving prior systemetic therapy are anticipated to be enrolled, and will be dosed camrelizumab (200 mg, iv, q3w) combined with etoposide (80-100 mg/m2, iv, q3w, 4-6 cycles) and platinum drugs (selected by the researcher accordingly, iv, q3w, 4-6 cycles), followed by maintenance with camrelizumab and apatinib (250 mg, qd). The primary endpoint is 6-month progress-free survival (6-month PFS) rate while the secondary endpoints are objective response rate (ORR), disease control rate (DCR), progression-free survival, overall survival and safety. Results: Up to January 24, 2024, 31 patients with a median age of 60 years (ranged from 38 to 75 years of age) were enrolled. Among them 28 patients out of 31 were capable for efficacy analysis, of which 23 patients achieved partial response, 3 had stable disease and 2 progressive disease. The ORR and DCR reached 82.14% and 92.86%, respectively. The 6-month PFS rate in evaluable patients was 75.44% and the median PFS was and 7.56 months. The median OS was 15.38 months. During the course of therapy, the grade 3 or worse treatment-related adverse events were hypertension (6.45%), increased ALT level(3.26%), increased AST level(3.26%), increased γ-GT(3.26%)and hypertriglyceridemia (3.26%). Common grade 1-2 adverse reactions included anemia(54.84%), nausea (54.84%), vomiting(45.16%). The treatment was well tolerated and no toxic death occurred. All the adverse events can be controlled and alleviated after symptomatic treatment. Conclusions: Camrelizumab with chemotherapy followed by maintenance camrelizumab plus apatinib showed preliminary efficacy and acceptable safety profile, and might be a promising regimen as first-line treatment in ES-SCLC. Clinical trial information: ChiCTR2000035599.
Preliminary results of a randomized controlled, open-label, multi-center phase II study of camrelizumab combined with chemotherapy followed by concurrent chemoradiotherapy and camrelizumab consolidation therapy versus standard chemoradiotherapy as first-line treatment for limited-disease small cell lung cancer.
Authors: Yaping Xu , Ni Jian , Ren Shengxiang , Xu Xiaoling , Hu Min , Xu Qinghua , Chen Yun , Zhu Yaoyao
Published: August 2024

e20132

Background: Immune checkpoint inhibitors combined with chemotherapy have significant clinical benefits in extensive-stage small cell lung cancer (SCLC). However, for patients with limited-disease SCLC (LD-SCLC), the data on immunotherapy combined with chemoradiotherapy is insufficient. Methods: In this open-label, multi-center, phase 2 trial, we randomly 1:1 assigned patients with previously untreated LD-SCLC to receive camrelizumab combined with chemotherapy followed by concurrent chemoradiotherapy (CCRT) and camrelizumab consolidation therapy or standard chemoradiotherapy. Patients with ECOG performance status of 0 to 1, and adequate organ function were eligible. For thoracic radiation, 45 Gy in 3 weeks (1.5 Gy, BID) was given on the first day of the third cycle of chemotherapy. An etoposide plus platinum-based regimen was given 4 cycles in total. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 1-year progression-free survival rate. We assumed that the 1-year PFS rate in the experimental group was expected to reach 65% compared to chemoradiotherapy alone group 45%, and planned to enroll 112 patients with 56 in each group. Results: Up to date, we have enrolled 40 patients. The median follow-up was 10.6 months. Safety was evaluated in all treated patients. No Grade 5 adverse event was observed. Grade 3 or 4 treatment-related adverse events occurred in 58.8% of the patients in the camrelizumab plus chemoradiotherapy and in 52.9% of those in the chemoradiotherapy alone group. The most frequent grade 3 or 4 adverse events were hematologic toxicities (70.6% vs. 58.8%). Acute esophagitis and pneumonitis of grade 3 occurred in both groups were 1/17 (5.9%) and 1/17 (5.9%), respectively. In the experimental group, only one patient was developed grade 3 immune pneumonia 1/17 (5.9%). The 1-year PFS rate was 54.5% (95% confidence interval [CI] 19.5%-89.6%) with camrelizumab plus chemoradiotherapy and 44.4% (95% CI 3.9%-88.0%) with chemoradiotherapy alone. Among the 17 patients who received camrelizumab, the median PFS time was not reached, as compared with 14.35 (95% CI, 8.15-20.91) months among the 17 patients with chemoradiotherapy alone. Conclusions: In patients with LD-SCLC, the addition of camrelizumab to chemoradiotherapy did not increase the incidence of adverse events. Camrelizumab plus chemoradiotherapy resulted in an encouraging 1-year PFS rate. Larger sample sizes and longer follow-up times are required to validate our preliminary results. Clinical trial information: ChiCTR2000032275.
Emerging Therapies for the Management of Human Epidermal Growth Factor Receptor 2–/ERBB2-Altered Advanced Biliary Tract Cancers
Authors: Zeme Emily L. , Van Loon Katherine , Kelley Robin K. , Gordan John D.
Published: August 2024

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.
A Novel Maternally Inherited GNAS Variant in a Family With Hyperphagia and Obesity: 3 Cases
Authors: Ramakrishnan Anand , Popat Dillon , Purushothaman Preetha , Chan Li F , Gevers Evelien F
Published: August 2024

GNAS variants were recently described in 1% of patients not known to have pseudohypoparathyroidism/inactivating PTH/PTHrP signalling disorder 2 in the UK Genetics of Obesity Study. We describe a new missense GNAS variant, c.791A > C, p.(Asp264Thr), in a family with obesity, hyperphagia and mild PTH resistance. A 6-year-old female (body mass index +4.3 SD score [SDS], height +1.9 SDS) presented with hyperphagia and obesity from age 3 years. She had subtle brachydactyly, macrocephaly, and mildly delayed development. The 12-year-old brother (height +2.1 SDS, body mass index +2.9 SDS) had hyperphagia, obesity, mildly delayed development, and autism. He had subtle brachydactyly, as did the affected mother. We assessed the functional effect of the mutant, measuring cAMP production in cells transfected with wild type and mutant GNAS after ligand stimulation. Cells with the mutant GNAS showed impaired cAMP generation through melanocortin receptor 4, GH releasing hormone receptor, and PTH receptor. These cases demonstrate the clinical heterogeneity of monogenic disease, suggesting a need to test for PHP1A in children with obesity even without classical signs of PHP1A.
Diabetes Stigma and Clinical Outcomes: An International Review
Authors: Eitel Kelsey B , Pihoker Catherine , Barrett Catherine E , Roberts Alissa J
Published: August 2024

Diabetes stigma is the social burden of living with diabetes. People with diabetes may experience or perceive an adverse social judgment, prejudice, or stereotype about living with diabetes at work, school, in healthcare settings, popular culture, or relationships. This review describes the methods that have been used to assess diabetes stigma, and explores the prevalence of diabetes stigma, associated sociodemographic and socioeconomic factors, cultural factors, and how diabetes stigma is associated with clinical outcomes, including HbA1c levels, diabetic ketoacidosis, severe hypoglycemia, and chronic complications, in addition to psychosocial complications in youth, adolescents, and adults with type 1 diabetes (T1D) and type 2 diabetes (T2D). The prevalence of diabetes stigma has been reported as high as 78% in adults with T1D, 70% in adults with T2D, 98% in youth and adolescents with T1D, and is unknown in youth and adolescents with T2D. Diabetes stigma has been associated with lower psychosocial functioning, decreased self-care behaviors, higher HbA1c levels, and higher frequency of diabetes complications in adults with T1D and T2D. In adolescents and young adults with T1D, diabetes stigma is associated with lower psychosocial functioning, higher HbA1c levels, and higher frequency of diabetic ketoacidosis and severe hypoglycemia episodes in addition to chronic complications. In youth and adolescents with T2D, one study demonstrated an association of diabetes stigma with lower psychosocial functioning, higher HbA1c levels, and presence of retinopathy. Gaps exist in our understanding of the mechanisms of diabetes stigma, particularly in youth and adolescents with T2D.
Wartime Economics in Italy: National Accounting and Economic Planning
Authors: Rancan Antonella
Published: August 2024

This article deals with the consequences of World War II on the study of national income and the changing approach to economic planning in Italy. It concentrates on Corrado Gini's original definition of national income in terms of well-being with respect to the meaning that will prevail after the war, which was instrumental for a planning policy. Both the development of an accounting system and attempts to implement economic planning contributed to the establishment of economic expertise and to the transformation of the language of economics.
Charles Bettelheim and World War II, or The Making of a Planning Doctor
Authors: Allisson François
Published: August 2024

The French Marxist economist Charles Bettelheim (1913–2006) conducted after the end of World War II important scientific activity on economic planning, together with an international consulting activity in developing countries, as a non-Soviet expert on Soviet planning. He was the Frenchman who whispered the Soviet way of planning in the ears of Nasser in Egypt, Nehru in India, and Che Guevara in Cuba, to mention only three obvious examples. The expression “planning doctors” is proposed in this article to designate this kind of economist who advised governments in the setting up of socialist five-year plans. In order to understand how Bettelheim became a planning doctor, the article reconstructs the formative period of his career and what role World War II played in this making, starting with his studies in political economy in France, his trip to the USSR in 1936, and his works on Soviet statistics. It is shown how World War II affected Bettelheim from an intellectual point of view, with his study of the German economy at war, and from an institutional point of view, as his encounters during the war proved instrumental for the setting of his postwar career as a planning doctor.
Analysis without Theory: How the Statistical Research Group Shaped Milton Friedman's Economic Methodology
Authors: Boumans Marcel
Published: August 2024

This article shows that Friedman's experiences with the research conducted at the Statistical Research Group (SRG) significantly shaped his 1953 methodology. These experiences gave him the ideas for a methodology for statistical analysis when dealing with “lousy data,” that is, when the conditions under which they are generated are not clear, when the data are “uncontrolled experiences.” Two views emerged from his SRG work. One is his view on theoretical assumptions: they only specify and do not determine under which conditions a model or device is expected to work. The other is his view on testing: the working of a device should be tested in comparison with a standard. Assessing the performance of a model with a benchmark model makes irrelevant the uncontrollable, only partly known, complex mass of circumstances under which both models perform. So both views were two sides of the same coin.
Introduction to Economists at War: How World War II Changed Economics (and Vice Versa)
Authors: Dupont-Kieffer Ariane , Dimand Robert W. , Rivot Sylvie
Published: August 2024

The 2023 HOPE conference aimed to understand the interrelationships between the Second World War and economics. Examining this back-and-forth means examining the transformative effect of the war on the content and status of economics but also symmetrically examining the role played by economics and economists in the conduct of the Second World War.