bluuebunny/crossref_metadata_2025 huggingface dataset:
ACE-Breast-02: A pivotal phase II/III trial of ARX788, a novel anti-HER2 antibody-drug conjugate (ADC), versus lapatinib plus capecitabine for HER2+ advanced breast cancer (ABC).
Authors: Hu Xichun , Wang Leiping , Zhang Jian , Zhang Qingyuan , Ouyang Quchang , Wang Xiaojia , Li Wei , Xie Weimin , Tong Zhongsheng , Xu Faliang , Liu Wei , Wang Shushen , Sun Tao
Published: August 2024

1020

Background: ARX788 is a next-generation ADC of HER2 monoclonal antibody site-specifically conjugated with Amberstatin 269, a potent cytotoxic tubulin inhibitor. Here we report the interim result from this seamless phase II/III trial in patients who progressed on trastuzumab based therapy. Methods: This randomized study was conducted in HER2+ (FISH+ or IHC3+) ABC in 85 centers in China. Patients with unresectable or metastatic breast cancer pretreated with trastuzumab and taxane were randomized 1:1 to receive ARX788 (1.5mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC, lapatinib 1250mg, QD; capecitabine 1000mg/m2 BID, d1-14, Q3W), stratified by previous chemotherapy lines (0-1 vs. >1) and visceral metastasis (yes vs. no). ARX788 was not pre-medicated with any prophylactic measures. Primary endpoint was progress-free survival (PFS) determined by Independent Review Committee (IRC). Results: As of Dec. 21, 2022, 221 patients were randomly assigned to ARX788 and 220 to LC, and 240 PFS events occurred. Efficacy results are listed in table 1. The median PFS was 11.33 months with ARX788 versus 8.25 months with LC as per IRC (HR 0.64, p=0.0006). Treatment-related adverse events (TRAEs) of any grade occurred in 98.6% (217/220) and 99.1% (213/215) of patients, respectively. TRAEs of grade 3-5 was similar in two groups (41.4% and 40.0%, respectively), commonest being blurred vision (12.3%), dry eye (9.1%), keratopathy (5.9%) and interstitial lung disease (5.9%) with ARX788 and hand-foot syndrome (18.1%), hypokalemia (5.1%), diarrhea (4.2%) with LC. 71 patients (32.3%) had interstitial lung disease with ARX788, primarily grade 1 or 2 (26.8%) with 3 (1.4%) possibly having drug-related deaths. 164 patients (74.5%) had ocular events related to ARX788, primarily grade 1 or 2 (55.5%) with no grade 4 or 5. Conclusions: ARX788 significantly prolonged PFS comparing to LC in patients with HER2+ ABC previously treated with trastuzumab and taxane. While ocular toxicity and interstitial lung disease were common and manageable, its hematological and GI toxicities under no prophylactic premedication compared favorably with already available ADCs. Clinical trial information: CTR20201708. [Table: see text]
Maintenance treatment with toripalimab and anlotinib after anthracycline-based chemotherapy in patients with advanced soft tissue sarcoma (TORAN): A single-arm, phase 2 trial.
Authors: Deng Yaotiao , Liu Jie , Li Mei , Jiang Yu
Published: August 2024

11572

Background: In patients with advanced soft tissue sarcoma (STS) who have achieved disease control after anthracycline-based chemotherapy, maintenance therapy is being explored. This study evaluated the efficacy and safety of toripalimab (a monoclonal antibody against the programmed cell death-1 receptor) combined with anlotinib (a multitargeted tyrosine kinase inhibitor) as a maintenance treatment. Methods: Patients with advanced STS who have achieved disease control after at least four cycles of first-line anthracycline-based chemotherapy were enrolled in this single-arm, phase 2 trial. Fifty patients are planned to receive treatment with toripalimab and anlotinib. The primary endpoint was progression-free survival rate at 24 weeks (PFR24w) during maintenance therapy. Secondary endpoints were median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: By the cut-off date of Jan 25, 2024, 22 patients were enrolled, including patients with leiomyosarcoma (n =5), synovial sarcoma (n =3), epithelioid sarcoma (n =3), dedifferentiated liposarcoma (n =2) and other different subtypes of sarcomas (n =9). The median follow-up time was 11 months. Response has been evaluated in 18 patients. The ORR and DCR were 22.2% and 100%. The PFR24w was 67%, the median PFS was 11.8 months, and the median OS was not reached. The grade 3 or higher adverse events were hypertension (n =4), hemorrhage (n =1), adrenal insufficiency (n =1) and hypertriglyceridemia (n =1). Conclusions: Maintenance therapy with toripalimab and anlotinib is a promising treatment option for patients with advanced STS after first-line anthracycline-based chemotherapy. Clinical trial information: ChiCTR2100054901.
Adjuvant S-1 vs. observation for resected biliary tract cancer: 5-year follow-up of the JCOG1202/ASCOT.
Authors: Nakachi Kohei , Ikeda Masafumi , Konishi Masaru , Mizusawa Junki , Katayama Hiroshi , Sano Yusuke , Uesaka Katsuhiko , Yanagimoto Hiroaki , Morinaga Soichiro , Wada Hiroshi , Shimada Kazuaki , Takahashi Yu , Nakagori Toshio , Gotoh Kunihito , Kamata Ken , Shimizu Yasuhiro , Ishii Hiroshi , Okusaka Takuji , Furuse Junji , Ueno Makoto
Published: August 2024

4119

Background: S-1, an oral fluoropyrimidine derivative, demonstrated significant improvement in overall survival (OS) over observation in patients with curatively resected biliary tract cancer (BTC) (hazard ratio [HR] 0.694, p=0.008; the 3-year OS, 67.6% vs. 77.1%, Lancet 2023). We present updated efficacy data based on a 5-year follow-up of JCOG1202/ASCOT. Methods: Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone R0/R1 resection were randomly assigned (1:1) to undergo observation or to receive S-1 (at the dose of 40 mg/m2 twice daily for 4 weeks, followed by 2 weeks of rest, for 4 cycles). The primary endpoint was OS, and the secondary endpoints were relapse-free survival (RFS), adverse events, and proportion of treatment completion. Results: From September 2013 to June 2018, a total of 440 patients (observation, n=222; adjuvant S-1, n=218) were enrolled. The final data cutoff date was June 23, 2023, and the median follow-up duration was 61.5 months. Of all the randomized patients, 215 (48.4%) had died (118 [53.2%] in the observation group; 97 [44.5%] in the S-1 group). The 5-year OS was 52.2% in the observation group and 64.1% in the S-1 group (stratified HR 0.723, 95% confidence interval [CI], 0.551-0.948; one-sided p=0.019). Of the 440 patients, 239 (54.3%) had RFS event (127 [57.2%] in the observation group; 112 [51.4%] in the S-1 group). The 5-year RFS was 45.9% in the observation group and 53.6% in the S-1 group (unstratified HR 0.797, 95% CI 0.618-1.028, stratified HR 0.761, 95% CI 0.589-0.984 in the sensitivity analysis). Most prespecified subgroup analyses (age, primary site, stage, lymph node metastases, types of resections, and serum CA19-9 levels) revealed favorable OS and RFS for the S-1 group. Conclusions: Adjuvant S-1 therapy maintained its survival benefit in a 5-year long-term follow-up, with clinically meaningful improvement in RFS, suggesting that it could be a standard of care for BTC. Clinical trial information: UMIN000011688.
A phase 2 study of trifluridine/tipiracil (FTD/TPI) in recurrent/metastatic nasopharyngeal (r/m NPC) carcinomas with or without prior exposure to fluoropyrimidines.
Authors: Low Jia Li , Chong Wan Qin , Hui Edwin Pun , Lai Winky , Le Candice , Sooi Kenneth , Walsh Robert John , Chan Anthony T. C. , Goh Boon C. , Ma Brigette
Published: August 2024

6032

Background: Despite effective local treatment, up to 30% of patients with nasopharyngeal carcinoma (NPC) relapse and require systemic treatment. There are limited therapeutic options beyond cisplatin, gemcitabine and immunotherapy and the median survival of r/m disease is about 20 months. Capecitabine, a fluoropyrimidine, has shown some efficacy with a median time to progression of 4.9 months in heavily pretreated r/m NPC but there is a need for alternative treatments. FTD/TPI is an oral drug combination of trifluridine and tipiracil, a thymidine phosphorylase inhibitor preventing rapid degradation of trifluridine, thus increasing its exposure. It has shown activity in colorectal, gastric and breast cancers despite prior fluoropyrimidines. This study explores the efficacy and safety of FTD/TPI in r/m NPC, with or without prior exposure to fluoropyrimidines. Methods: In this single-arm phase II trial, patients were administered oral FTD/TPI twice daily at 35mg/m2 on days 1-5 and 8-12 of a 28-day cycle. The primary endpoint was disease control rate (DCR) at 12 weeks, with secondary endpoints including progression-free survival (PFS), overall response rate (ORR), safety, and tolerability. Results: A total of 33 patients were recruited. Median age was 56 years (range: 34-82), most were males (n=27, 82%), with median of 3 (range: 1-12) prior lines of treatment in the metastatic setting. Approximately half (48.5%) received prior fluoropyrimidines. DCR at 12 weeks was 63.6%, with an ORR of 18.2%. DCR was 68.8% and 58.8% in patients with and without prior fluoropyrimidine exposure respectively. Median PFS was 6.5 months (95% CI 2.8-10.2) and overall survival was 13.1 months (95% CI 7.1-19.2). FTD/TPI demonstrated a manageable safety profile, with most common treatment-related adverse events of neutropenia, anaemia, fatigue, nausea and anorexia. 60% of patients required dose modifications, most commonly due to neutropenia, that could be overcome by dose reduction or prolongation to 5-weekly cycles. 1 patient required discontinuation due to anaemia resulting in syncope. Conclusions: FTD/TPI is well tolerated, compares favorably to Capecitabine and showed promising anti-tumor activity with meaningful clinical benefit regardless of prior exposure to fluoropyrimidines. This oral chemotherapy offers an attractive choice for patients valuing quality of life, minimizing hospital visits and resource utilization such as chemotherapy infusions. Further investigations in randomized studies are warranted. Clinical trial information: NCT04627961 .
Treatment discontinuation due to toxicity for patients with acute myeloid leukemia (AML) treated on SWOG S1203.
Authors: Raychaudhuri Suravi , Othus Megan , Percival Mary-Elizabeth M. , Garcia-Manero Guillermo , Appelbaum Frederick R. , Erba Harry Paul , Appelbaum Jacob
Published: August 2024

6529

Background: Curative-intent therapy for patients with newly diagnosed AML centers on the use of cytarabine as part of an intensive multi-drug induction regimen. Treatment-related toxicity may lead to patients stopping treatment, despite the considerable risk of inadequately treated AML. We compared rates of protocol therapy discontinuation due to adverse events (AEs) in either of two standard induction regimens (7+3 or high dose cytarabine + idarubicin, IA) on the S1203 study (Garcia-Manero; Leukemia 2023). Methods: S1203 was a randomized study of patients <60 years old with newly diagnosed AML. Patients were required to have performance status (PS) <3, ejection fraction >45%, and no prolonged QTc interval or known cardiac disease. There were no exclusion criteria for kidney or liver function. On the 7+3 induction arm, subjects received daunorubicin 90 mg/m2 IV daily days 1-3 with continuous infusion cytarabine 100 mg/m2 daily days 1-7. On the IA arm, subjects received idarubicin 12 mg/m2 daily days 1-3 with continuous infusion cytarabine 1.5 g/m2 daily days 1-4. Toxicities were assessed per the Common Terminology Criteria for Adverse Events version 4.0. Rates of discontinuation were compared using Fisher’s exact test. Results: From 4/2013-11/2015, 522 subjects were randomized (261 to each arm). Treatment discontinuation due to either death or toxicity occurred in 8 vs 22 patients on 7+3 vs IA respectively (p=0.014). During induction, 0 patients on the 7+3 arm discontinued treatment due to toxicity versus 4 patients on the IA arm (0% vs 2%; p=0.12). Toxicities leading to treatment discontinuation on the IA arm included congestive heart failure (n=2, one with concurrent arrhythmia), acute kidney injury (n=1), and hypotension complicated by stroke and cardiac arrest (n=1). Two of the 4 patients who discontinued treatment due to toxicity on IA achieved a complete remission after their first cycle. For patients with PS 2-3 (n=40 on 7+3, n=27 on IA), rates of grade 3-5 AEs were 85% vs 86% and rates of grade 5 AEs were 0% vs 11% (p=0.065). Conclusions: 7+3 was well tolerated. Excluding patients from S1203 with PS 2-3 or decreased hepatic/renal function would not have prevented treatment-related toxicity. The low rate of protocol therapy discontinuation due to toxicity suggests that eligibility criteria for clinical trials could be further broadened to improve patient access. Clinical trial information: NCT0180233 . [Table: see text]
Preliminary efficacy and safety of total neoadjuvant therapy combined with PD-L1 blockade in pMMR/MSS locally advanced rectal cancer (ESTIMATE): A prospective, single-arm, phase II trial.
Authors: Zhang Xuan , Feng Qing , Cai Xinyi , Yu Kun , Shen Tao , Pan Dingguo , Tan Jing , Ju Yunhe , Zhang Lijuan , Xie Lin , Dong Jianhua , Xia Cuifeng , Xiong Wei , Yang Quan , Wu Tao , Li Yun-Feng
Published: August 2024

e15602

Background: Patients with locally advanced rectal cancer (LARC) experience benefits from total neoadjuvant therapy (TNT). This study aims to explore the efficacy and safety of combining TNT with immunotherapy for pMMR/MSS LARC patients. Methods: ESTIMATE is a prospective, single-center, phase II study (ChiCTR2400079718) enrolling pMMR/MSS LARC patients with tumors located 10cm away from the anal margin. Treatment involved induction chemotherapy with immunotherapy ([mFOLFOX6, days 1-2 + Envafolimab 200mg, ih, day 1]; q2w; 2 cycles), long-course concurrent chemoradiotherapy (LCRT) with immunotherapy ([IMRT, 50Gy/25f, 2Gy + Cape 825mg/m2, bid]; 5w + Envafolimab 200mg, ih, day 1; q2w; 3 cycles), consolidation chemotherapy with immunotherapy ([mFOLFOX6 + Envafolimab; 2 cycles), and then total mesorectal excision (TME) 3 weeks later or watch and wait (W&W). The primary endpoint is the pathological complete response (pCR) rate. Results: Until Nov. 16th, 2023, 35 patients were enrolled, with 28 completing the TNT regimen. The efficacy analysis revealed that out of 28 patients, 12 (42.9%) achieved clinical complete response (cCR), with 7 individuals choosing the W&W strategy. 21 patients underwent TME, yielding 8 with a tumor regression grade (TRG) of 0, 7 with TRG of 1, and 6 with TRG of 2. The rates of pCR, major pathological response (MPR), and complete response (CR) were 38.1% (8/21), 71.4% (15/21), and 53.6% (15/28), respectively. 25 (89.3%) patients experienced treatment-related adverse events (AEs) of any grade. Non-hematological AEs included decreased appetite, fatigue, nausea, and vomiting, while hematological AEs mainly comprised thrombocytopenia, anemia, and leukopenia or neutrophilia. Grade III AEs were primarily leukopenia or neutrophilia (2/28, 7.1%). Additionally, circulating tumor DNA (ctDNA) levels were measured in 7 patients who chose the W&W strategy after achieving cCR. Of these, 6 tested negative for minimal residual disease (MRD), while 1 had a positive MRD result (ctDNA: 0.56 MTM/ml). As of Jan. 26th, 2024, with a median follow-up of 5 months (range: 3-6), no recurrence was observed in any of the patients. Conclusions: The TNT approach, integrating LCRT with mFOLFOX6 and PD-L1 blockade, demonstrated a favorable CR rate and acceptable tolerability, offering a potential avenue for organ preservation in low rectal cancer patients with pMMR/MSS. Long-term benefits need validation through further follow-up. Clinical trial information: ChiCTR2400079718. [Table: see text]
Bevacizumab Erlotinib Switch Maintenance in Chemo-Responsive Advanced Gallbladder and Cholangiocarcinoma (BEER BTC): A Multicenter, Open-Label, Randomized, Phase II Trial
Authors: Ramaswamy Anant , Bhargava Prabhat , Srinivas Sujay , Kapoor Akhil , Mishra Bal Krishna , Gupta Anuj , Mandavkar Sarika , Kannan Sadhana , Chaugule Deepali , Patil Rajshree , Parulekar Manali , Nashikkar Chaitali , Ankathi Suman Kumar , Kaushal Rajiv Kumar , Naughane Deepali , Daddi Anuprita , Mer Neha , Shetty Nitin , Ostwal Vikas
Published: August 2024

PURPOSE

Patients with chemotherapy-responsive advanced biliary tract cancers (BTCs) are usually observed after 6 months of gemcitabine-based therapy. There is limited prospective evidence for maintenance strategies after chemotherapy.

METHODS

This investigator-initiated, open-label, randomized, integrated phase II-III study enrolled adult patients with advanced BTC from two cancer centers in India. Patients with histologically confirmed advanced biliary tract adenocarcinoma who had at least disease stabilization after 6 months of gemcitabine-based chemotherapy were randomly assigned (1:1) to either active surveillance or switch maintenance, which was a combination of bevacizumab 5 mg/kg intravenous once every 21 days plus erlotinib 100 mg once daily. Both arms were continued until disease progression, unacceptable toxicity, or patient decision to withdraw. The primary end point of the phase II component of the trial was investigator-evaluated progression-free survival. This trial is registered with Clinical Trials Registry of India (CTRI/2019/05/019323I).

RESULTS

From May 2021 to November 2022, 98 patients were randomly assigned to active surveillance (n = 49) or bevacizumab-erlotinib (n = 49). A majority of patients had gallbladder cancer (80%). The median follow-up was 13.4 months. The median progression-free survival was 3.1 months (95% CI, 2.47 to 3.64) in the active surveillance group versus 5.3 months (95% CI, 3.53 to 7.04) in the bevacizumab-erlotinib group (hazard ratio, 0.51 [95% CI, 0.33 to 0·74]; P = .0013). The most common grade 3 class-specific adverse events associated with bevacizumab-erlotinib were acneiform rash 1 (2%) and oral stomatitis 1 (2%) with erlotinib and bleeding 1 (2%) with bevacizumab.

CONCLUSION

The combination of bevacizumab and erlotinib as switch maintenance improves progression-free survival with an acceptable safety profile compared with active surveillance in patients with advanced BTCs in this phase II study. The trial moves on to the phase III component to evaluate improvement in overall survival.
Impact of Age on Pharmacogenomics and Treatment Outcomes of B-Cell Acute Lymphoblastic Leukemia
Authors: Yoshimura Satoshi , Li Zhenhua , Gocho Yoshihiro , Yang Wenjian , Crews Kristine R. , Lee Shawn H.R. , Roberts Kathryn G. , Mullighan Charles G. , Relling Mary V. , Yu Jiyang , Yeoh Allen E.J. , Loh Mignon L. , Saygin Caner , Litzow Mark R. , Jeha Sima , Karol Seth E. , Inaba Hiroto , Pui Ching-Hon , Konopleva Marina , Jain Nitin , Stock Wendy , Paietta Elisabeth , Jabbour Elias , Kornblau Steven M. , Evans William E. , Yang Jun J.
Published: August 2024

PURPOSE

Acute lymphoblastic leukemia (ALL) can occur across all age groups, with a strikingly higher cure rate in children compared with adults. However, the pharmacological basis of age-related differences in ALL treatment response remains unclear.

METHODS

Studying 767 children and 309 adults with newly diagnosed B-cell ALL enrolled on frontline trials at St Jude Children's Research Hospital, MD Anderson Cancer Center, the Alliance for Clinical Trials in Oncology, and the ECOG-ACRIN Cancer Research Group, we determined the ex vivo sensitivity of leukemia cells to 21 drugs. Twenty-three ALL molecular subtypes were identified using RNA sequencing. We systematically characterized the associations between drug response and ALL genomics in children, adolescents and young adults, and elderly adults. We evaluated the effect of age-related gene expression signature on ALL treatment outcomes.

RESULTS

Seven ALL drugs (asparaginase, prednisolone, mercaptopurine, dasatinib, nelarabine, daunorubicin, and inotuzumab ozogamicin) showed differential activity between children and adults, of which six were explained by age-related differences in leukemia molecular subtypes. Adolescents and young adults showed similar patterns of drug resistance as older adults, relative to young children. Mercaptopurine exhibited subtype-independent greater sensitivity in children. Transcriptomic profiling uncovered subclusters within
CRLF2
-,
DUX4
-, and
KMT2A
-rearranged ALL that were linked to age and cytotoxic drug resistance. In particular, a subset of children had adult-like ALL on the basis of leukemia gene expression patterns across subtypes, despite their chronological age. Resistant to cytotoxic drugs, children with adult-like ALL exhibited poor prognosis in pediatric ALL trials, even after adjusting for age and minimal residual diseases.

CONCLUSION

Our results provide pharmacogenomic insights into age-related disparities in ALL cure rates and identify leukemia prognostic features for treatment individualization across age groups.
Murmurs of Presence in Objects of Absence
Authors: Feldman Ilana
Published: August 2024

This article takes two artifacts belonging to two people the author met in the course of many decades of research in and on Palestine—a British Mandate-era identity card and a set of framed photographs of a Palestinian village destroyed in the Nakba (catastrophe) of 1948—as central objects of consideration in reflecting on how objects of absence incorporate historical and personal loss as well as continuing presence. The use of the term “objects of absence” to describe these materials points to how they are more than repositories of memory. They record, preserve, and animate forms of life that appear lost. Rather than being noisy eruptions into public life, their volume is more of a murmur. Their collective impact is in their repeated presence rather than their spectacular pronouncements. Palestinians preserve these objects for themselves, for their children and following generations, for their community, and for their nation. The work of these objects is thus personal and political, individual and collective. They help people locate themselves in the world, maintaining some continuity despite the devastation of the Nakba.
Open-source, high-throughput targeted in situ transcriptomics for developmental and tissue biology
Authors: Lee Hower , Langseth Christoffer Mattsson , Salas Sergio Marco , Sariyar Sanem , Metousis Andreas , Rueda-Alaña Eneritz , Bekiari Christina , Lundberg Emma , Garcı́a-Moreno Fernando , Grillo Marco , Nilsson Mats
Published: August 2024

Multiplexed spatial profiling of mRNAs has recently gained traction as a tool to explore the cellular diversity and the architecture of tissues. We propose a sensitive, open-source, simple and flexible method for the generation of in situ expression maps of hundreds of genes. We use direct ligation of padlock probes on mRNAs, coupled with rolling circle amplification and hybridization-based in situ combinatorial barcoding, to achieve high detection efficiency, high-throughput and large multiplexing. We validate the method across a number of species and show its use in combination with orthogonal methods such as antibody staining, highlighting its potential value for developmental and tissue biology studies. Finally, we provide an end-to-end computational workflow that covers the steps of probe design, image processing, data extraction, cell segmentation, clustering and annotation of cell types. By enabling easier access to high-throughput spatially resolved transcriptomics, we hope to encourage a diversity of applications and the exploration of a wide range of biological questions.
Biaxial seismic response of base-column connections in sub-standard steel buildings: dataset
Authors: Stathas Nikolaos , Di Sarno Luigi , Wu Jingren , Freddi Fabio , D’Aniello Mario , Bousias Stathis , Landolfo Raffaele , Güneyisi Esra Mete , Papagiannis Lambros
Published: August 2024

Existing steel frames not complying with modern seismic codes are often vulnerable to earthquakes due to inadequate seismic detailing. These types of framed structures typically feature semi-rigid and partial strength column-base connections; the behaviour of such connections may significantly affect their seismic performance. However, current code provisions offer limited guidance for the assessment and retrofit of column-base connections To fill the knowledge gap, the H2020 EU-funded Earthquake Assessment of Base-Column Connections in Existing Steel Frames (HITBASE) project experimentally investigated, the response of exposed column-base plate connections. Bi-directional Pseudo-Dynamic tests were carried out at the Structures Laboratory (STRULAB) of the University of Patras within the framework of Engineering Research Infrastructures for European Synergies (ERIES). The case-study steel frame featured two types of column-base plate connections, i.e., stiffened and unstiffened, representing respectively the base connections of an external moment-resisting frame and an internal gravity frame. The experimental programme comprised free vibration tests to identify the modal properties of the sample steel frame. A set of quasi-static cyclic tests and Pseudo-Dynamic tests were then carried out to investigate the performance of the steel frame under bi-directional earthquake sequences. The response of each component constituting the column-base plate connections was monitored during the tests to fully capture the behaviour of the connections. Such experimental results allow model calibration and further parametric investigation on column base plate connections.
Navigating the challenges of passenger name record data and the way forward
Authors: Aposkiti Christiana , Makri Freideriki
Published: August 2024

Background The TENACITy EU-funded project investigates the multifaceted challenges surrounding the utilisation of Passenger Name Record (PNR) data following the implementation of the PNR Directive (EU) 2016/681, which marks a significant shift in EU air travel intelligence. Methods This study employed a combination of research and survey methodologies to gather data from various stakeholders involved in the implementation of the PNR Directive. The survey focused on identifying the key obstacles faced by Passenger Information Units (PIUs), including the absence of standardised practices and issues of data quality. Results The findings highlight two primary obstacles confronting PIUs: the lack of standardised practices among stakeholders and the poor quality of PNR data. Additionally, fragmented implementation and regulatory barriers were identified as significant hindrances to the optimal utilisation of PNR data for counterterrorism and crime prevention efforts. Conclusions Addressing these challenges requires nuanced solutions, with technological tools presenting potential remedies to operational constraints. There is a collective call for mandating specific data elements to enhance the effectiveness of PNR data utilisation. This paper provides insights and recommendations to enhance PIUs' capabilities, contributing to the ongoing discourse on EU travel intelligence.
Co-designing ab initio electronic structure methods on a RISC-V vector architecture
Authors: Grima Torres Rogeli , Vizcaíno Pablo , Mantovani Filippo , Gutiérrez Moreno José Julio
Published: August 2024

Ab initio electronic structure applications are among the most widely used in High-Performance Computing (HPC), and the eigenvalue problem is often their main computational bottleneck. This article presents our initial efforts in porting these codes to a RISC-V prototype platform leveraging a wide Vector Processing Unit (VPU). Our software tester is based on a mini-app extracted from the ELPA eigensolver library. The user-space Vehave and a RISC-V vector architecture implemented on an FPGA were tested. Metrics from both systems and different vectorisation strategies were extracted, ranging from the most simple and portable one (using autovectorisation and assisting this by fusing loops in the code) to the more complex one (using intrinsics). We observed a progressive reduction in the number of vectorial instructions, executed instructions and computing cycles with the different methodologies, which will lead to a substantial speed-up in the calculations. The obtained outcomes are crucial in advancing the porting of computational materials and molecular science codes to (post)-exascale architectures using RISC-V-based technologies fully developed within the EU. Our evaluation also provides valuable feedback for hardware designers, engineers and compiler developers, making this use case pivotal for co-design efforts.
The PRECISE-DYAD Neurodevelopmental substudy protocol: neurodevelopmental risk in children of mothers with pregnancy complications
Authors: Magai Dorcas N. , Chandna Jaya , Volvert Marie-Laure , Craik Rachel , Jah Hawanatu , Kongira Fatoumata , Bojang Kalilu , Koech Angela , Mwashigadi Grace , Mutua Agnes M. , Blencowe Hannah , D'Alessandro Umberto , Roca Anna , Temmerman Marleen , von Dadelszen Peter , Abubakar Amina , Gladstone Melissa ,   The PRECISE DYAD Network
Published: August 2024

Background Over 250 million children are not reaching their developmental potential globally. The impact of prenatal factors and their interplay with postnatal environmental factors on child neurodevelopment, is still unclear—particularly in low- and middle-income settings. This study aims to understand the impact of pregnancy complications as well as environmental, psychosocial, and biological predictors on neurodevelopmental trajectories. Methods This is an observational cohort study of female and male children (≈3,950) born to women (≈4,200) with and without pregnancy complications (pregnancy-induced hypertension, foetal growth restriction, and premature birth) previously recruited into PREgnancy Care Integrating Translational Science, Everywhere study with detailed biological data collected in intrapartum and post-partum periods. Children will be assessed at six weeks to 6 months, 11-13 months, 23-25 months and 35-37 months in rural and semi-urban Gambia (Farafenni, Illiasa, and Ngayen Sanjal) and Kenya (Mariakani and Rabai). We will assess children's neurodevelopment using Prechtls General Movement Assessment, the Malawi Development Assessment Tool (primary outcome), Observation of Maternal-Child Interaction, the Neurodevelopmental Disorder Screening Tool, and the Epilepsy Screening tool. Children screening positive will be assessed with Cardiff cards (vision), Modified Checklist for Autism in Toddlers Revised, and Pediatric Quality of Life Inventory Family Impact. We will use multivariate logistic regression analysis to investigate the impact of pregnancy complications on neurodevelopment and conduct structural equation modelling using latent class growth to study trajectories and relationships between biological, environmental, and psychosocial factors on child development. Conclusions We aim to provide information regarding the neurodevelopment of infants and children born to women with and without pregnancy complications at multiple time points during the first three years of life in two low-resource African communities. A detailed evaluation of developmental trajectories and their predictors will provide information on the most strategic points of intervention to prevent and reduce the incidence of neurodevelopmental impairments.
Determination of ivermectin in plasma and whole blood using LC-MS/MS
Authors: Kaewkhao Natpapat , Hanpithakpong Warunee , Tarning Joel , Blessborn Daniel
Published: August 2024

Background Ivermectin is a widely used drug for the treatment of helminthiasis and filariasis worldwide, and it has also shown promise for malaria elimination through its potent mosquito-lethal activity. The objective of this study was to develop and validate a high-throughput and sensitive method to quantify ivermectin in plasma and whole blood samples, using automated sample extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods Phospholipids were removed in patient whole blood (100 µl) and plasma (100 µl) samples using a 96-well plate Hybrid-solid phase extraction technique. Ivermectin and its isotope-labelled internal standard (ivermectin-D2) were separated on an Agilent Poroshell 120 EC-C18 50mm × 3.0mm I.D. 2.7µm, using a mobile phase of acetonitrile: ammonium formate 2 mM containing 0.5% formic acid (90: 10, v/v). Detection was performed using a triple quadrupole mass spectrometer in the positive ionization mode. Results The method was validated in the concentration range 0.970 - 384 ng/ml in both plasma and whole blood matrices. Intra- and inter-batch precisions during the validation were below 15%. There was no carryover or matrix effects detected. Ivermectin is a stable compound and results showed no degradation in the different stability tests. Conclusions The validated method proved to have high sensitivity and precision, good selectivity and to be suitable for clinical application or laboratory quantification of ivermectin in plasma or whole blood samples.
ADHD - Treatment Options and Consequences of Neglect
Authors: Wojciechowska Klara , Turek Monika , Jaroń Aleksandra , Jastrzębska Katarzyna , Witkowska Maria , Skotnicka Joanna , Błaszczak Karolina , Borkowski Adrian , Sawicki Mateusz
Published: August 2024

Purpose of Research: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most frequently diagnosed neurodevelopmental disorders. It is estimated to occur in approximately 5-10% of children and adolescents. This paper aims to highlight the challenges faced by individuals suffering from ADHD, present risk factors, summarize current treatment methods, and outline the consequences of neglecting treatment.
Methods: Databases such as PubMed, Medline, and ResearchGate were used.
Basic Results: The goal of ADHD treatment is to reduce the severity of symptoms and improve the social, academic, and emotional functioning of children and adolescents. The choice of treatment and the selection of a specific medication depend on the patient's age and coexisting disorders.
Conclusions: ADHD often coexists with other mental disorders, complicating diagnosis and treatment. Lack of or ineffective treatment has consequences such as learning difficulties, disruptions in peer and family relationships. It correlates with higher rates of traffic accidents, accidental injuries, earlier onset, and higher rates of substance abuse.
Can a Supplier’s Yield Risk Be Truthfully Communicated via Cheap Talk?
Authors: Lu Tao
Published: August 2024

Problem definition: When a firm (buyer) outsources the production of a new product/component to a supplier subject to random yield, a major challenge is that the supplier’s yield is usually private information. In practice, yield information is often shared via nonbinding communication—for example, a supplier self-assessment report. We examine whether such communication can be truthful and credible. Methodology/results: We analyze a cheap-talk game in which, given a simple contract that specifies the prices for each unit ordered and for each effective unit delivered, the supplier first communicates its yield level, and then the buyer determines an order quantity. We prove that truthful communication can emerge in equilibrium. To do so, we first show that if knowing the supplier’s type, the buyer will either inflate or reduce the order quantity to cope with a lower yield, depending on the product’s market potential. Under asymmetric information, the supplier will truthfully communicate its type if (i) the buyer with a high market potential intends to inflate the order quantity for a lower yield, but the buyer with a low market potential prefers to do the reverse; and (ii) the supplier is uncertain about the product’s market potential, which is the buyer’s private information, and anticipates that a hard-to-make product is more likely to have a higher market potential. Managerial implications: Truthful cheap-talk communication can emerge in equilibrium when the product’s market size and yield are negatively correlated. Truthful communication always benefits the buyer and consumers and may benefit the supplier if the product has sufficient market potential and the supplier’s production cost is not too high. Moreover, the buyer can be better off paying more for the input quantity (although part of the output is defective) or paying a higher wholesale rate if the adjustment in payment terms enhances communication credibility.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0089 .
Syphilis should not be overlooked in any individual, irrespective of their condition
Authors: Cellier Oriane , Jourdan Juliette , Dahmane Lotfi , Perronne Véronique , Dinh Aurélien , Jaffal Karim
Published: August 2024

Introduction: Syphilis remains a significant challenge in public health, largely because of its diverse clinical manifestations, often resulting in underdiagnosis especially among patients with neurogenic disability. Case description: We present a case of neurosyphilis in a 63-year-old patient with a spinal cord injury. Despite syphilis being a well-established sexually transmitted infection, the exacerbation of neurological and dermatological symptoms during physical examination prompted an investigation into alternative causes beyond the patient’s pre-existing paraparesis, ultimately resulting in the diagnosis of neurosyphilis. Conclusion: This case highlights the importance of considering syphilis as a potential diagnosis in individuals regardless of their medical history.
An unusual case of HHV-8 negative, idiopathic, multicentric Castleman disease following chronic lymphocytic leukaemia
Authors: Sansen Pierre-Yves , Vellemans Hélène , Depaus Julien , Fervaille Caroline , Krug Benoit , Sonet Anne , Collinge Elodie
Published: August 2024

Background: Castleman disease is a rare condition characterised by polytypic lymphocytes proliferation and lymphadenopathy generally with a benign course. Whereas high grade lymphoma (Richter syndrome) is a classical complication seen in chronic lymphocytic leukaemia with a poor outcome, benign conditions mimicking this entity are infrequent. Case description: We describe the case of an 81-year-old Caucasian male who developed a human herpesvirus-8 (HHV-8)–negative, idiopathic multicentric Castleman disease (iMCD) following a treated Binet C chronic lymphocytic leukaemia (CLL). The clinical and radiological pattern raised initially the suspicion of a classical Richter transformation. Blood analysis showed auto-immune haemolytic anaemia and thrombocytopenia. He had normal immunoglobulin levels. The anatomopathological analysis of a cervical adenomegaly showed hypervascularisation and a polytypic plasmocytic proliferation compatible with a plasmocytic iMCD type. Interestingly, bone marrow examination showed reticuline fibrosis but, in the absence of anasarca or generalised oedema, we were not allowed to conclude to the diagnosis of a TAFRO syndrome. We exclude all other mimicking conditions, comprising haematological malignancies, infections, and auto-immune diseases He was first treated with corticosteroids with poor results but dramatically responded to tocilizumab (anti-Il6). Conclusion: To our knowledge, this the first case described of a Castleman disease following CLL and surprisingly mimicking Richter syndrome. Clinicians should be aware of this rare misleading condition.
Time to treatment of first-episode psychosis: the role of early intervention teams
Authors: Hall Michael , Mills Rachel , Watson Edward , Nathan Rajan , Stewart Alex G
Published: August 2024

Background/Aims

Psychosis can affect a person's functioning, quality of life and physical health. Early intervention for service users presenting with psychosis has been implemented via early intervention teams, but there are inconsistencies in assessment and treatment. The aim of this study was to examine time to treatment (defined as the commencement of antipsychotic medication) for service users experiencing first-episode psychosis, the impact of this and engagement with teams. The authors explored the effect of patient characteristics (eg gender, deprivation, ethnicity, age) and early intervention teams on time to treatment for psychosis.

Methods

A retrospective cohort study was undertaken using routine data of service users accessing three early intervention teams from 2018–19. The care records of 457 service users were examined, including patient characteristics, assessments, time to first contact, treatment and time to discharge. Data were analysed using the Statistical Package for Social Sciences.

Results

Use of the Positive and Negative Syndrome Scale assessment tool differed across the three early intervention teams. Engagement with all teams varied by gender. Men were particularly slow to access treatment in one team (118 of 163 service users, 72.4%).

Conclusions

Increased emphasis on engaging male patients may improve service delivery. Improved communication between early intervention teams could increase standardisation of assessment and treatment.
Investigating swollen joints in dogs and cats
Authors: Freeman-Mills Georgia , A Corr Sandra
Published: August 2024

Dogs and cats can present with acute or chronic swollen joint(s) which may or may not be associated with concurrent systemic signs of illness. Joint swelling may occur spontaneously, or with a history of trauma or previous surgery. Such cases can pose a diagnostic challenge, and understanding the underlying pathophysiology relating to the potential diagnoses is key to informing further investigations, achieving a prompt diagnosis and initiating appropriate early treatment. No diagnostic test should be interpreted in isolation, and every case requires thorough history taking, physical examination and selective use of blood testing and imaging. In conjunction with this, arthrocentesis in an invaluable tool suitable for general practice as well as referral practice. Practitioners should be encouraged to use arthrocentesis early in the diagnostic process to guide their management of patients with swollen joints, thereby optimising patient outcomes.
Plant diversity and its use in Javanese urban home garden: An ethnobotanical study in Central Java, Indonesia
Authors: DARMASTUTI SALMA ARDELIA , NAZAR IRFAN ABU , SETYAWAN AHMAD DWI
Published: August 2024

Abstract. Darmastuti SA, Nazar IA, Setyawan AD. 2024. Plant diversity and its use in Javanese urban home garden: An ethnobotanical study in Central Java, Indonesia. Asian J Ethnobiol 7: 32-42. Urbanization makes the spread of botanical knowledge increasingly widespread. Ethnobotanical knowledge brought by village communities can be applied in urban areas. The implementation of Proklim (Climate Village Program) by the Indonesian Government strengthens the development of environmentally friendly cities that are able to adapt and overcome climate change and are sustainable by paying attention to the balance of social, economic, and environmental aspects. Currently, communities and home gardens have responded to various driving factors, such as the environmental movement and urban sustainability, and are more focused on providing healthy local food and community development. The objectives of this study were to find out the medicinal and food plants found in the home gardens and community gardens of ProKlim RW 16 Banjarsari Village, Banjarsari Sub-district, Surakarta City, Central Java, Indonesia and the influence felt by the community and knowing the existence of ProKlim RW 16 to support the 13th Sustainable Development Goals (SDGs), climate action. The method used is descriptive quantitative, which is conducted through observation, interviews, and questionnaires. Data from observations and interviews were calculated using the formula of Use Value, Relative Frequency of Citation, Informant Consensus Factor, and Fidelity Level. Meanwhile, questionnaire data is calculated using the Likert Scale calculations. The research results show 56 species that residents often use for medicinal and food plants. The most widely used medicinal plant is lemongrass (Cymbopogon citratus (DC.) Stapf), and the most widely used food plant is chili (Capsicum frutescens L.). Based on Likert Scale calculations, the adaptation indicator states that 90.25% of respondents agree that food plants grown by themselves are fresher and healthier. Meanwhile, on the mitigation indicator, 93.39% of respondents agreed that the more plants planted could reduce air pollution and lower the earth's temperature.
Pollinator insects in the Mount Tumpa Forest Park, Manado, North Sulawesi, Indonesia
Authors: KONERI RONI , LANGOY MARNIX D. , NANGOY MEIS J. , WAKHID WAKHID
Published: August 2024

Abstract. Koneri R, Langoy MD, Nangoy MJ, Wakhid. 2024. Pollinator insects in the Mount Tumpa Forest Park, Manado, North Sulawesi, Indonesia. Biodiversitas 25: 2415-2426. This study aimed to analyze the diversity and distribution of pollinator insects in forest, forest edge, shrub, and agricultural land around the Mount Tumpa Forest Park, Manado, North Sulawesi, Indonesia, using the scan sampling method. Data analysis included species abundance, species dominance, richness index, diversity index, species evenness index, correlation between environmental factors, species diversity, and composition of pollinator insect species among habitats. Therefore, 17 families were reported, comprising 103 species and 3,665 individuals. The family with the highest number and most frequently encountered was Nymphalidae (25 species). Furthermore, the highest species richness and diversity indices were found in the forest edge habitat. Environmental factor analysis indicated that agricultural land habitat was characterized by high air temperature and low humidity. The species distribution found three patterns: clustered, regular, and random. The results showed that the forest edge habitat had the highest diversity due to complex vegetation structure and environmental factors supporting the survival of pollinator insects.
Improvement of antimicrobial activity of Pediococcus pentosaceus strain 2397 in suppressing Escherichia coli
Authors: RIFTYAN EMMA , YUSMARINI YUSMARINI , ROSSI EVY , PATO USMAN
Published: August 2024

Abstract. Riftyan E, Yusmarini, Rossi E, Pato U. 2024. Improvement of antimicrobial activity of Pediococcus pentosaceus strain 2397 in suppressing Escherichia coli. Biodiversitas 25: 2500-2506. Lactic acid bacteria exhibit antibacterial activity that suppresses spoilage and pathogenic bacteria. Due to their antagonistic action against foodborne pathogens such as Escherichia coli, LAB isolated from dairy products have attracted considerable attention as a potential food preservative. Furthermore, bioactive compounds generated by forming LAB biofilms may exhibit efficacy against pathogenic microorganisms and their toxin. Combining LAB biofilms and other LAB products, such as bacteriocins, could offer a significant method against pathogenic microorganisms and their biofilms. The aim of this study was to evaluate the effects of optimization of media composition and incubation conditions on the antimicrobial activities of cell-free supernatant (CFS) from Pediococcus pentosaceus strain 2397 to inhibit E. coli FNCC-19. The antimicrobial activity of CFS was determined using agar well diffusion method. The results revealed that antimicrobial activity of P. pentosaceus strain 2397 was enhanced by optimizing the media composition and incubation conditions. Pediococcus pentosaceus strain 2397 exhibited excellent antimicrobial activity against E. coli. In MRS, 5% (v/v) of P. pentosaceus strain 2397+2.0% (w/v) yeast extract with pH 7.0 showed an inhibition zone of 10.44 mm. Therefore, strain 2397 may be effective in producing bacteriocin as a preservative for food products.