bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining the potency of a neoantigen-expressing DNA vector, an anti-CTLA-4 antibody, and an attenuated poxvirus in a personalized immunization platform: Preclinical studies of ODI-2001.
Authors: Marschall Pierre , Matta Celia , Hugel Cécile , Matta Jessica , Bogaert Cedric , Ghiringhelli François , Balducchi Pascale , Limacher Jean-Marc
Published: June 2024

e14674

Background: Immune checkpoint inhibitors (ICI) have transformed cancer treatment. Their impressive effectiveness is crucially dependent on pre-existing neoepitope-specific immune responses. ODI-2001 aims at increasing the immune response against tumors by combining a DNA expressing multiple neoepitopes of the tumor, a MVA vaccinia virus as physiologic adjuvant and DNA carrier, and an anti-CTLA4 antibody as amplifier of the immune response. Methods: ODI-2001 was administered by repeated subcutaneous injections after tumor cells implantation in mice melanoma model B16F10 and colorectal cancer model CT26, and both before and after implantation in breast cancer model 4T1. In B16F10 model combination of ODI-2001 with anti-PD1 was assessed also. Neoepitopes were chosen from literature in B16F10 and CT26 models. In 4T1 model they were predicted using a dedicated neoepitope prediction algorithm (ImmunoEngine, myNEO, Gent, Belgium). Tumor volume and mice survival were assessed over time. Tumors were also analysed by immunofluorescence for immune cell infiltration. Each experiment received approval from the ethics committee for animals. Results: A significant improvement in survival was observed in mice treated with ODI-2001 in B16F10, and CT26 syngeneic mice models. In B16F10 the combination of ODI-2001 with anti-PD1 antibody demonstrated synergistic activity and a significant improvement in survival, while anti-PD1 alone or combined with anti-CTLA-4 failed to show any therapeutic effect (ODI-2001 + anti-PD1 vs. anti-CTLA-4 + anti-PD1 p<0.01). ODI-2001 treatment was associated with tumor rejections in the three animal models. In 4T1 model the ImmunoEngine epitope prediction algorithm demonstrated an improved efficacy as compared to a set of neoepitopes chosen from the literature. In B16F10, following immunization with ODI-2001, an increased CD8 immune cell infiltration of the tumor was documented. ODI-2001 was well tolerated by the treated animals. Conclusions: These data demonstrate a significant antitumoral activity of ODI-2001 as a neoantigen immunization platform across different preclinical cancer models, both in monotherapy and combined with anti-PD1. ODI-2001 represents a promising option to induce de novo cancer-specific immune responses, potentially increasing the proportion of patients responding to immunotherapy treatments. Based on this preclinical program a phase I with ODI-2001 in patients with advanced colorectal carcinoma is currently under preparation.
Preliminary results from a first-in-human trial of AMT-116, a topoisomerase I inhibitor containing antibody-drug conjugate (ADC), in patients with advanced solid tumors.
Authors: Coward Jim , Kichenadasse Ganessan , Park John J. , Parakh Sagun , Richardson Gary Edward , Voskoboynik Mark , Powderly John D. , Song Zhengbo , Liu Shutong , Huang Yaling , Liu Shu-Hui , Meng Xun
Published: June 2024

e15010

Background: CD44v9 is a tumor-associated antigen highly expressed in various solid tumor types including head and neck, lung, esophageal, pancreatic, colorectal, breast, bladder, hepatic, cervical, and gastric cancers. AMT-116 is a first-in-class antibody-drug conjugate (ADC) targeting CD44v9, by conjugating a novel topoisomerase I inhibitor, belotecan derivative named KL610023 (Sichuan Kelun-Biotech) to a humanized anti-CD44v9 immunoglobulin G1 (IgG1) antibody via a hydrolysable linker with an average drug-to-antibody ratio of 7-8. Methods: This is an ongoing first-in-human, non-randomized, open-label, multicenter, Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of AMT-116 in patients (pts) with advanced solid tumors, unselected for target expression. Pts received escalating doses of AMT-116 Q2W starting from 1.5 mg/kg guided by the Bayesian logistic regression model (BLRM) following escalation with overdose control (EWOC) principle. Results: As of Feb 1, 2024, eight pts (4 pts at 1.5 mg/kg, 3 pts at 3 mg/kg and 1 pt at 5 mg/kg) have been treated in Australia and pts at 1.5 mg/kg and 3 mg/kg completed the 28-day dose-limiting toxicity (DLT) evaluation period. No DLT events were observed, and the maximum tolerated dose (MTD) has not been reached. Treatment related adverse events (TRAEs) were reported in 5 pts out of 8. The most common TRAEs were fatigue (n=3) and nausea (n=3). Only one Grade 3 TRAE (leukopenia) was reported. There were no Grade 4 or 5 TRAEs or treatment-related SAEs. Seven pts have completed at least one post-treatment tumor assessment. At dose level 3 mg/kg, one pt with anal squamous cell carcinoma achieved unconfirmed PR with a 31% tumor shrinkage and one pt with hepatocellular carcinoma achieved SD with a 23% tumor shrinkage from baseline. Subject enrollment in 5 mg/kg is underway. Conclusions: These preliminary data indicate that AMT-116 is well tolerated at the first two dose levels in patients with heavily pretreated advanced solid tumors. Dose escalation is ongoing. Clinical trial information: NCT05725291 .
Effect of sodium thiosulfate anhydrous on cisplatin-induced ototoxicity in pediatric cancers: Turkish compassionate use treatment protocol—Updated results.
Authors: Unal Emel Cabi , Tacyildiz Nurdan , Canpolat Cengiz , Ataseven Eda , Sivrice Ayse Cigdem , Sevinir Betul , celik Ates Dilvin , Tuncel Tolga
Published: June 2024

e15075

Background: Cisplatin induced ototoxicity (CIO), with permanent hearing loss is observed in >60% pediatric patients in Turkey. PEDMARK (Sodium Thiosulfate anhydrous) reduced the risk of CIO cases with non-metastatic solid tumors observed in Phase 3 studies (SIOPEL 6 & COG ACCL0431). We aimed to evaluate the investigational product PEDMARK provided for pediatric cases via a National Compassionate Use Treatment Protocol (CUP) in Turkey. Methods: Patients (1 month to <18 years) with a localized, nonmetastatic solid tumor, standard-risk hepatoblastoma (HBB), nasopharyngeal carcinoma (NPC) and medulloblastoma MB whose treatment plans were including cisplatin were eligible. PEDMARK was administered intravenously 6 hours after each cisplatin dose infusion. Adverse events, demography, pre and post- hearing were recorded from 21OCT2019-21SEPT2022. Results: The CUP enrolled 12 patients, 8 HBB, 3 NPC and 1 MB in 3 years, from 6 academic institutions. HBB patients' median age was 1year (3mos-3 yrs). All pts had newly diagnosed HBB PRETEXT 3 (n = 5) with a median baseline AFP OF 54.000. 3 NPC age 13-17 yrs, MB 6yrs of age. All patients had Brock Grade 0 on hearing tests prior to treatment Patients received a median 0f 6 cycles (range 4-6) of cisplatin and PEDMARK. Patients with hearing tests available post-treatment (n=11), all maintained Brock Grade 0. At a median of 0.8mos post-treatment, CR were observed in all patients except one HBB with progressive disease. All CRs wer sustained 18.8 mos. AEs in 2 patients were Grade 1-2 nausea/vomiting, no Grade >3 AEs were reported. Conclusions: PEDMARK was well tolerated, provided via a Turkish CUP to reduce the CIO in pediatric patients with nonmetastatic solid tumors. No hearing loss was observed/ detected post-treatment and the tumor outcomes were consistent with the Phase 3 studies. This is very encouraging.
First-in-human study of HMPL-295, an ERK1/2 inhibitor, in patients with advanced solid tumors: Dose-escalation results of monotherapy.
Authors: Yu Xianjun , Zhang Jian , Sun Yuping , Deng Yanhong , Guo Shuangshuang , Hong Wei , Shi Si , Liu Rujiao , Gao Shuiping , Dang Qi , Zhang Jianwei , Su Weiguo , Shi Michael , Fan Songhua , Zhang Bo , Pan Beiqing , Jia Xiaoyun , Wang Jian , Zhong Chen , Ma Luguang
Published: June 2024

e15112

Background: HMPL-295 (’295) is an extracellular signal-regulated kinase 1 and 2 (ERK1/2) inhibitor with potent activity in non-clinical studies. This is a first-in-human, dose escalation study of ’295 in patients (pts) with advanced solid tumors. Here, we report the results of the mono dose escalation stage. Methods: Pts with advanced solid tumors who have failed standard therapy were enrolled to receive ’295 once daily (QD) in 28-day cycles or ’295 QD 2 weeks on/1 week off (2w on/1w off) in 21-day cycles. The mTPI-2 design was used for dose escalation, having explored from 5 to 75 mg QD in 6 cohorts, as well as 75 mg and 100 mg QD 2w on/1w off. The study aims to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and preliminary efficacy (best of response, BOR). Results: As of Dec 11, 2023, 47 pts with advanced solid tumors were enrolled (n=1, 1, 3, 6, 12, 5, 13, 6 in 5, 10, 20, 40, 50, 75 mg QD cohorts, 75, 100 mg QD 2w on/1w off cohorts, respectively), with a median age of 58 years, 23 (48.9%) male pts. During the dose escalation from 5 to 75 mg QD cohort, 1 pt given 40 mg QD experienced a dose-limiting toxicity (DLT) of grade 3 dermatitis acneiform and 2 pts given 75 mg QD experienced DLTs of grade 3 rash and acute kidney injury (AKI). As for intermittent-administration cohorts, 2 pts given 100 mg QD 2w on/1w off experienced DLTs of grade 3 AKI and rash maculo-papular. After multiple-dose oral administration, ’295 plasma concentrations reach peak at 1.0-2.0 hours post dose and the exposure (Cmax and AUC) displayed dose dependent increase. The accumulation ratio (AUC) was 2.1–3.4 after repeat dosing, reaching steady-state around day 15. ’295 inhibited ribosomal S6 kinase (RSK) phosphorylation which is a downstream signaling molecule regulated by ERK1/2 and stimulated by phorbol 12-myristate 13-acetate (PMA). The BOR was partial response each in 1 pt with duodenal adenocarcinoma in 40 mg QD cohort,1 pt with endometrial cancer in 50 mg QD cohort and 1 pt with non-small cell lung cancer (NSCLC) in 75 mg QD 2w on/1w off cohort. Stable disease with tumor shrinkage was also observed in 2 pts with NSCLC on 50 mg QD and 75 mg QD 2w on/1w off cohort respectively, and 1 pt with pancreatic ductal adenocarcinoma in 100 mg QD 2w on/1w off cohort. 25 (53.2%) pts reported grade ≥3 TEAEs. The most common (≥10.0%) ≥ grade 3 TEAEs were rash (10.6%) and anemia (10.6%). Conclusions: Considering safety, tolerability, PK/PD and preliminary efficacy results, RP2D was determined to be 50 mg QD. Clinical trial information: NCT04908046 .
Incidence and potential prognostic implications of fibroblast growth factor receptor gene alterations and coexisting mutations in colorectal cancer.
Authors: Lea Vivienne , Lim Stephanie Hui-Su , Chua Wei , Ng Weng Leong , Wang Bin , Wilkinson Kate Jessica , Farzin Mahtab , Habashy Paul , Roberts Tara , Becker Therese , Lee Cheok Soon
Published: June 2024

e15558

Background: The fibroblast growth factor receptor (FGFR) family comprises four tyrosine kinase receptors (FGFR1-4). FGFR1 amplification (6.3%) as well as overexpression of FGFR1 (10.1%), FGFR2 (5.5%) and FGFR3 (16.2%) have been demonstrated in primary colorectal cancer (CRC, incidence in brackets). The prognostic utility of testing FGFR alterations and association with response to FGFR-inhibitors are still emerging. Here, we report FGFR alteration data with clinicopathological correlations and survival outcomes from a Sydney based Local Health District in Australia. Methods: Clinicopathological data was analysed from 341 ethnically diverse patients with CRC treated at Southwestern Sydney Local Health District from 2014-2021. Next generation sequencing for point mutations, deletions, and amplifications was performed using the Qiagen 30-gene panel. Mismatch repair (MMR) status was determined using immunohistochemical staining. Demographic characteristics, histological features and survival outcomes were recorded from electronic medical records. Results: Of the 341 patients, 42 (12.3%) had FGFR alterations of which 52% were men and 48% women. 32 patients were Caucasian, 4 Middle Eastern, 5 Asian and 1 South American. Median age at diagnosis was 66 years. Of the 42 patients, FGFR1 mutations were present in 26.2%, FGFR1 amplifications in 4.7% and FGFR1 deletions in 4.7%. FGFR2 mutations were present in 16.7%, and 50% had FGFR3 mutations. One patient had concurrent FGFR1 and FGFR3 mutations. The vast majority were adenocarcinoma (81%), followed by mucinous adenocarcinoma (17%) and adenocarcinoma with neuroendocrine features (2%). 21.4% of patients with FGFR alterations had concurrent KRAS mutations, 28.6% had concurrent BRAF mutations (91.6% V600E) and MMR-deficiency was present in 19%. Median overall survival of patients with FGFR alterations was 44 months, for those who also had deficient MMR 48 months, concurrent BRAF V600E mutations 51 months and concurrent KRAS mutations 71 months. 43% (18 patients) were stage 4 at presentation. Of these 18 patients, 7 had FGFR1 mutations, 1 had a FGFR2 mutation and 10 had FGFR3 mutations. The median overall survival of patients with stage 4 disease was 11 months and those with concurrent BRAF V600E mutations 17 months. Two patients had concurrent KRAS mutations (both G12V), with median overall survival of 5.5 months and 1 patient had MMR deficiency, with an overall survival of 9 months. Conclusions: FGFR alterations were identified in 12.3% of patients with colorectal cancer in an ethnically diverse cohort in Australia. Concurrent KRAS and BRAF mutations appear to affect survival outcomes. Further multivariate analyses are underway.
The impact of treatment approach on survival among patients with clinical stage T2N0 and T3N0 rectal cancer.
Authors: Rehman Tauseef Ur , Ceballos Natalie , Samuels Shenae , Ferraro Pablo H. , Gannon Christopher J. , Llaguna Omar H.
Published: June 2024

e15637

Background: Treatment of early stage rectal cancer requires a multi-disciplinary approach and is often treated with curative intent surgery with use of total neoadjuvant treatment (TNT) or neoadjuvant chemoradiotherapy (nCRT) in select cases pre-operatively. In this study, we determine the various clinicopathologic factors associated with the use of these different approaches (Surgery upfront vs nCRT vs TNT) and their effect on patient survival. Methods: The National Cancer Database (NCDB) was queried for patients with clinical T2N0M0 and T3N0M0 rectal cancer between 2004-2019. Results: 36,869 patients were identified, of which about half had nCRT only while < 15% had received TNT. Patients who underwent nCRT had the highest median OS compared to those who underwent surgery only (106.8 vs 126.5 months, p < 0.001). The surgery upfront cohort had the highest proportion of patients who were seen at a facility with high/very high case volume per year quartiles (surgery: 52.5%, nCRT: 47.3%, and TNT: 48.3%, p < 0.001). The highest median age was among the surgery cohort at 69 years followed by the nCRT cohort at 64 years and TNT cohort at 61 years (p < 0.001). Amongst patients with a Charlson-Deyo co-morbidity score of 2 or more, the surgery upfront cohort had the highest proportion while the TNT cohort had the lowest (p < 0.001). Low anterior resection (LAR) was the most common procedure among all three cohorts. A multivariate logistic regression model revealed that when compared to surgery only, the nCRT (Adjusted Odds Ratio (AOR) = 1.51, p < 0.001) and TNT (AOR = 1.62, p < 0.001) were both associated with an increased likelihood of 5-year long-term survival (LTS), with TNT having a stronger association. Among the various pre-operative characteristics, patients 70 years and older, patient with normal CEA and presence of LVI were less likely to have LTS with TNT as compared to surgery upfront. On the other hand, patients with clinical T3 stage who received TNT were much more likely to have improved LTS as compared to T2 stage (Relative Risk Ratio (RRR) 16.19, p < 0.001). Conclusions: Results of our study show that patients with early stage T2N0 and T3N0 rectal cancer who underwent neoadjuvant treatment had an improved median OS compared to patients who received surgery upfront. Both nCRT and TNT were associated with an increased likelihood of long-term survival, with TNT having a stronger association particularly in the T3N0 cohort.
Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole
Authors: Chapman Judith-Anne W. , Bayani Jane , SenGupta Sandip , Bartlett John M.S. , Piper Tammy , Quintayo Mary Anne , Virk Shakeel , Goss Paul E. , Ingle James N. , Ellis Matthew J. , Sledge George W. , Budd G. Thomas , Rabaglio Manuela , Ansari Rafat H. , Tozer Richard , D'Souza David P. , Chalchal Haji , Spadafora Silvana , Stearns Vered , Perez Edith A. , Gelmon Karen A. , Whelan Timothy J. , Elliott Catherine , Shepherd Lois E. , Chen Bingshu E. , Taylor Karen J.
Published: June 2024

PURPOSE

ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes.

METHODS

MA.27 (ClinicalTrials.gov identifier: NCT00066573 ) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤–1; (–1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05.

RESULTS

Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS ( P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated ( P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS ( P = .001) in models with ER.

CONCLUSION

Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤–1.
Improved HbA1c and Body Weight in GADA-Positive Individuals Treated With Tirzepatide: A Post Hoc Analysis of SURPASS
Authors: Peters Anne L , Buzzetti Raffaella , Lee Clare J , Pavo Imre , Liu Minzhi , Karanikas Chrisanthi A , Paik Jim S
Published: June 2024

Context

People with clinically diagnosed type 2 diabetes (T2D) but positive antiglutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits.

Objective

This work aimed to assess glycated hemoglobin A1c (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive vs GADA-negative participants with a clinical T2D diagnosis.

Methods

Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status, were conducted on 3791 individuals. Intervention included tirzepatide (5, 10, 15 mg). Main outcome measure included change from baseline in HbA1c at weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4) by GADA status.

Results

In participants with confirmed GADA status, 3671 (96.8%) were GADA negative and 120 (3.2%) were GADA positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive vs GADA-negative participants (mean [SD] BMI 32.2 [6.1] vs 33.6 [6.3]). At week 40/42, both groups achieved robust reductions in HbA1c (−2.11% vs −2.32%) and BW (–9.2 kg vs −9.6 kg) (P < .001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; P = .024) and BW reductions did not differ between groups (0.38 kg [−0.99, 1.75]; P = .588).

Conclusion

In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.
The Capitalist Manifesto: Why the Global Free Market Will Save the World
Authors: Carliner Geoffrey
Published: June 2024

Geoffrey Carliner of Boston Committee on Foreign Relations reviews “The Capitalist Manifesto: Why the Global Free Market Will Save the World” by By Johan Norberg. The EconLit abstract of this book begins: “Assesses the role of freedom and choice in capitalism, promoting the view that arguments against capitalism fail to take into account how capitalist competition has largely led to improvements in global standards of living.”
Avoiding Conflict
Authors: Roper Jack
Published: June 2024

Flight trials in Europe and the USA of unmanned drone operations are finally removing the operational and regulatory roadblocks to unmanned drone flights in integrated airspaces
Future Tools
Authors: Eden Paul E
Published: June 2024

The flight testing of Bombardier’s EcoJet sustainability R&D platform is producing data and tools, but not necessarily a whole aircraft
Ask The Expert
Authors: Sampson Ben
Published: June 2024

Experts give their insights into the latest technologies and emerging trends impacting metrology end users in the aerospace sector
Robot Jets at the Ready
Authors: Coppinger Rob
Published: June 2024

An increase in flight deck automation is laying the building blocks for a fully autonomous business jet
Frames of Innovation
Authors: Willis Paul
Published: June 2024

Engineers are finidng a variety of uses for high-speed cameras in engine testing
Made in Orbit
Authors: Millard Frank
Published: June 2024

R&D spend is increasing as governments and industry look to explore and commercially exploit space
50 Years of GPS
Authors: Sampson Ben
Published: June 2024

This month marks 50 years since the US Department of Defense funded the first GPS program
Taking Account
Authors: Norman Helen
Published: June 2024

The California Air Resources Board speaks to Electric & Hybrid Rail Technology about why its new In-Use Locomotive Regulation is so important for the state, highlighting how it will accelerate decarbonization, reduce emissions and save lives
The Big Switch
Authors: Kaur Mankirat
Published: June 2024

Sierra Northern Railway is embarking on a green revolution, which will see it convert its diesel-powered fleet to hydrogen power. EHRT spoke to the firm’s president, Kennan Beard, to find out more
Economy Drive
Authors: Roper Jack
Published: June 2024

With energy prices rising and increased pressure on transitioning away from diesel, rail firms are on the search for new ways to reduce traction energy consumption. EHRT explores the solutions on offer
At your Service
Authors: Allan Keri
Published: June 2024

Electric & Hybrid Rail Technology takes a close look at Europe’s test battery train maintenance and charging facilities
Pushing the Limits
Authors: Soltau Nils , Hatori Kenji , Tsuda Ryo
Published: June 2024

Mitsubishi Electric explores how highly efficient silicon carbide power semiconductors are set to play a big role in future railway traction systems
The Right Connection
Authors: Harting
Published: June 2024

Harting discusses how its inter-car jumper solutions can be adapted for individual customer demands, meeting requirements for both new trains and for retrofit projects around the world
Ready to Roll
Authors: Kuhn Marco
Published: June 2024

RECOM discusses the challenges of finding ready to use DC/DC power converters, designed with a wide input range to cover multiple nominals, surges, dips, and drop-outs in rail applications
Keeping Watch
Authors: Rohner Matthias
Published: June 2024

Bender is providing its latest insulation monitoring devices to Turkish projects to ensure traction converters developed in the country for current and future rolling stock are both safe and efficient
Medium-Voltage Silicon Carbide Solution for Rail
Authors: Satheesh Nitesh
Published: June 2024

Microchip addresses challenges in high voltage IGBT design with its mSiC products featuring silicon carbide (SiC) technology, offering design flexibility and enhanced efficiency.
Renin-angiotensin system inhibitor prescriptions in Chinese hospitalized chronic kidney disease patients
Authors: Zhang Chun , Duan Zhi-Yu , Nie Sa-Sa , Zhang Zhou , Guo Xin-Ru , Zhang Chao-Yang , Dong Jing , Cai Guang-Yan
Published: June 2024

BACKGROUND

Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.

AIM

To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.

METHODS

It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.

RESULTS

A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age < 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions.

CONCLUSION

The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.
Cerebral pseudoinfarction due to venoarterial extracorporeal membrane oxygenation: A case report
Authors: Xu Mi , Yan Jue-Yue , Jin Jia-Jia , Li Tong
Published: June 2024

BACKGROUND

Neurological complications are common in the management of venoarterial extracorporeal membrane oxygenation (VA-ECMO), with most patients requiring sedation and intubation, limiting the assessment of neurological function. There-fore, we must rely on advanced neuroimaging techniques, such as computed tomography angiography (CTA) and computed tomography perfusion (CTP). Because ECMO changes the normal blood flow pattern, it may interfere with the contrast medium in some special cases, leading to artifacts and ultimately mis-leading clinical decisions.

CASE SUMMARY

A 61-year-old man presented to a local hospital with chest tightness and pain 1 d prior to presentation. The patient was treated with VA-ECMO after sudden car-diac and respiratory arrest at a local hospital. For further treatment, the patient was transferred to our hospital. The initial consciousness assessment was not clear, and routine CTP was performed to understand the intracranial changes, which suggested a large area of cerebral infarction on the right side; however, the cerebral oxygen was not consistent with the CTP results, and the reexamination of CTA still suggested a right cerebral infarction. To identify this difference, bedside transcranial Doppler was performed, and the blood flow on both sides was different. By reducing the ECMO flow, CTP reexamination showed that the results were normal and consistent with the clinical results. On day 3, the patient was alert and showed good limb movements.

CONCLUSION

In patients with peripheral VA-ECMO, cerebral perfusion confirmed by CTP and CTA may lead to false cerebral infarction.
Ilizarov technique for treating elbow stiffness caused by myositis ossificans: A case report
Authors: Zhou Ming-Wang , Zhang Peng-Wei , Zhang An-Le , Wei Chang-Hao , Xu Yu-De , Chen Wei , Fu Zhi-Bin
Published: June 2024

BACKGROUND

Myositis ossificans (MO) is a rare disease involving the formation of bone outside the musculoskeletal system. While surgical intervention is the main treatment approach, preventing recurrence and standardized rehabilitation are also crucial. Here, we present a surgical strategy to prevent the recurrence of MO.

CASE SUMMARY

A 28-year-old female patient was admitted for the first time for a comminuted fracture of the left olecranon. However, incorrect postoperative rehabilitation resulted in the development of elbow joint stiffness with ectopic ossification, causing a loss of normal range of motion. The patient was diagnosed with MO based on physical examination, X-ray findings, and clinical presentation. We devised a surgical strategy to remove MO, followed by fixation with an Ilizarov frame, and implemented a scientifically reasonable rehabilitation plan. The surgery lasted for 3 h with an estimated blood loss of 45 mL. A drainage tube was placed after surgery, and fluid was aspirated through ultrasound-guided puncture. The patient experienced a significant reduction in joint stiffness after surgery. In the final follow-up at 9 mouths, there was evident improvement in the range of motion of the elbow joint, and no other symptoms were reported.

CONCLUSION

The Ilizarov frame is an advantageous surgical technique for facilitating rehabilitation after MO removal. It offers benefits such as passive recovery, individualized treatment, and prompt recovery.
Natural history and surgical treatment of a giant colonic diverticulum: A case report
Authors: Bachelani Arshad M
Published: June 2024

BACKGROUND

While diverticular disease is prevalent in the West, the formation of giant colonic diverticula is rare. To date, approximately 200 cases have been reported, with only a handful treated surgically using a minimally invasive approach. Furthermore, the natural history of giant colonic diverticula is not well documented.

CASE SUMMARY

This report describes the case of a 66-year-old man who developed a giant colonic diverticulum with primary symptoms including dull and chronic pain in the right lower quadrant at presentation. The patient had undergone several computed tomography scans of the abdomen and pelvis over the previous two years, through which the natural history of this rare entity could be retrospectively observed. The patient was successfully treated with a robot-assisted sigmoid colectomy and had an uneventful recovery with resolution of symptoms during the follow-up.

CONCLUSION

This rare case demonstrates the natural history of giant colonic diverticulum formation and supports the feasibility of robot-assisted surgery.
3D AUTOMATED VERSUS MANUAL ASSESSMENT OF ALIGNMENT IN NORMAL AND CAVUS FEET USING WEIGHT-BEARING CT SCANS: DOES IT DIFFER?
Authors: Sangoi D. , Ranjit S. , Bernasconi A. , Cullen N. , Patel S. , Welck M. , Malhotra K.
Published: June 2024

Background

The complex deformities in cavovarus feet may be difficult to assess and understand. Weight-bearing CT (WBCT) is increasingly used to evaluate complex deformities. However, the bone axes may be difficult to calculate in the setting of severe deformity. Computer-assisted 3D-axis calculation is a novel approach that may allow for more accurate assessment of foot alignment / deformity. The aim of this study was to assess differences in measurements done manually on 2D slices of WBCT versus 3D computer models in normal and cavus feet.

Methods

We retrospectively analyzed WBCT scans from 16 normal and 16 cavus feet in patients with Charcot-Marie Tooth. Eight measurements were assessed: Talus-1st metatarsal angle (axial plane), Forefoot arch angle (coronal plane), and Meary's angle, calcaneal pitch, cuneiform to floor, cuneiform to skin, navicular to floor and navicular to skin distance (sagittal plane). 2D measurements were performed manually and 3D measurements were performed using specialised software (BoneLogic, DISIOR).

Results

There was no significant difference in the measured variables (2D manual versus 3D automated) in normal feet. In the cavus group, 3D assessment calculated increased values for the sagittal angles: Meary's 7.3 degrees greater (p = 0.004), calcaneal pitch 2.4 degrees greater (p = 0.011)), and lower values for the axial talus-1st MT angle, 10.6 degrees less (p = 0.001).

Conclusion

There were no significant differences in the normal group. This suggests 3D automated techniques can reliably assess the alignment of bony axes. However, the 3D axis calculations suggest there may be greater sagittal and lesser axial deformity in cavus feet than measured by 2D techniques. This discrepancy may be on account of the rotation seen in cavovarus feet, which may not be readily assessed manually. 3D automated measurements may therefore have a role in better assessing and classifying the cavus foot which may ultimately help inform treatment algorithms.
PREVALENCE OF SYMPTOMATIC VENOUS THROMBOEMBOLISM IN PATIENTS WITH DIABETIC FEET TREATED IN TOTAL CONTACT CAST IN A TERTIARY REFERRAL DIABETIC FOOT UNIT
Authors: Kozhikunnath A. , Garg P. , Coll A. , Robinson A. HN
Published: June 2024

Introduction

Total contact casting (TCC) is one of the most commonly utilized modalities in the management of diabetic feet. We undertook a retrospective review to determine the prevalence of symptomatic VTE events in patients treated in a weight bearing TCC in our diabetic foot unit, and to formulate guidelines for VTE prophylaxis.

Methods

Electronic records were reviewed to identify all patients treated in a TCC between 2014 and 2021. Data collection included patient demographics, comorbidities, period of immobilization in TCC, the incidence of VTE events, and any VTE prophylaxis prescribed during their period in TCC.

Results

549 patients were identified who had at least one episode of TCC. Mean age was 67 years (range 28 to 94 years) and the mean duration in cast was 10.2 weeks (range 0.3–46 weeks). Only 6 patients (1.1%) were prescribed chemical thrombo-prophylaxis during their period in TCC. Mean body mass index (BMI) for these patients was 32.3 (Range 18.4–58.9). Other significant comorbidities: 81% (n-444) of patients had associated cardio-vascular comorbidities; 54 % (n-296) had renal comorbidities including 22% (n-121) having had dialysis and 4.2% (n-23) with renal transplants. Eight of the 549 patients (1.5%) had suffered a VTE event of which only 2 (0.36%) were during the period of immobilization in TCC. One was a symptomatic DVT (0.18%) and the another was an asymptomatic (incidental) finding of pulmonary embolism (PE). There was no mortality related to the VTE episodes.

Conclusion

NICE guidelines state that one should “Consider pharmacological VTE prophylaxis for patients with lower limb immobilization”. Our study finds that patients treated in a weight bearing TCC do not require routine pharmacological VTE prophylaxis, in spite of an extended period of lower limb immobilization and significant medical comorbidities.
Tip-apex distance as a risk factor for cut-out in cephalic double-screw nailing of intertrochanteric femur fractures
Authors: Coviello Michele , Abate Antonella , Maccagnano Giuseppe , Ippolito Francesco , Nappi Vittorio , Abbaticchio Andrea M. , Caiaffa Elio , Caiaffa Vincenzo
Published: June 2024

Aims

Proximal femur fractures treatment can involve anterograde nailing with a single or double cephalic screw. An undesirable failure for this fixation is screw cut-out. In a single-screw nail, a tip-apex distance (TAD) greater than 25 mm has been associated with an increased risk of cut-out. The aim of the study was to examine the role of TAD as a risk factor in a cephalic double-screw nail.

Methods

A retrospective study was conducted on 112 patients treated for intertrochanteric femur fracture with a double proximal screw nail (Endovis BA2; EBA2) from January to September 2021. The analyzed variables were age, sex, BMI, comorbidities, fracture type, side, time of surgery, quality of reduction, pre-existing therapy with bisphosphonate for osteoporosis, screw placement in two different views, and TAD. The last follow-up was at 12 months. Logistic regression was used to study the potential factors of screw cut-out, and receiver operating characteristic curve to identify the threshold value.

Results

A total of 98 of the 112 patients met the inclusion criteria. Overall, 65 patients were female (66.3%), the mean age was 83.23 years (SD 7.07), and the mean follow-up was 378 days (SD 36). Cut-out was observed in five patients (5.10%). The variables identified by univariate analysis with p < 0.05 were included in the multivariate logistic regression model were screw placement and TAD. The TAD was significant with an odds ratio (OR) 5.03 (p = 0.012) as the screw placement with an OR 4.35 (p = 0.043) in the anteroposterior view, and OR 10.61 (p = 0.037) in the lateral view. The TAD threshold value identified was 29.50 mm.

Conclusion

Our study confirmed the risk factors for cut-out in the double-screw nail are comparable to those in the single screw. We found a TAD value of 29.50 mm to be associated with a risk of cut-out in double-screw nails, when good fracture reduction is granted. This value is higher than the one reported with single-screw nails. Therefore, we suggest the role of TAD should be reconsidered in well-reduced fractures treated with double-screw intramedullary nail.

Cite this article: Bone Jt Open 2024;5(6):457–463.
Domestic Advice and Its Shadowy Double: Domestic Satire in At Home with Amy Sedaris
Authors: Bayne Caroline N.
Published: June 2024

ABSTRACT: Domestic advice media has persisted in the United States for over three centuries, yet images of the mid-twentieth-century homemaker serve as its most referential figure. Televisual domesticity consists of programs offering advice on homemaking, hosting, and crafting. Programs feature prominently on Food Network and HGTV in which white, upper-middle-class women choose to stay home and tend to the family. Alongside these traditional forms of domestic advice, this article considers the work of Amy Sedaris and feminist artists who utilize a blend of critical intertextuality, satire, and nostalgia toward the creation of a parallel, responsive genre—domestic satire.
Sins of Omission
Authors: Isserman Maurice
Published: June 2024

ABSTRACT: John Proctor Jr., a Puritan settler of Salem Village, Massachusetts Bay Colony, was convicted of witchcraft in a Salem court on August 5, 1692, and hanged two weeks later. He was one of twenty men and women executed in the Salem witchcraft trials.
Fragments of a New World
Authors: Lobo Nicole-Ann
Published: June 2024

ABSTRACT: A photograph of Sita Valles dressed in a paisley blue miniskirt with a hand on her hip, leaning against a glossy red car, has made the young revolutionary an icon. It appears on book covers, posters, and a mural in Panjim, the capital of Goa, India. In Two Refusals (Would We Recognize Ourselves Unbroken?) , a film by the Goan-American artist Suneil Sanzgiri recently on view at the Brooklyn Museum, Sita's brother Edgar Valles, a lawyer living in Portugal, tells her story.
The World of the Radical Right
Authors: Abrahamsen Rita , Adler-Bell Sam , Vucetic Srdjan , Williams Michael C.
Published: June 2024

ABSTRACT: The following is an edited transcript of a panel held on February 21 at the University of Pennsylvania's Perry World House on the forthcoming book World of the Right: Radical Conservatism and the Global Order (Cambridge University Press). The discussion, moderated by Sam Adler-Bell, features three of the book's co-authors—Rita Abrahamsen, Srdjan Vucetic, and Michael C. Williams—and concludes with questions from the audience at the event.
Terrorism Investigations on Campus and the New McCarthyism
Authors: O'Rourke Anthony , Said Wadie E.
Published: June 2024

ABSTRACT: In the 1960s, the FBI's counterintelligence program (COINTELPRO) routinely infiltrated campus antiwar and civil rights groups, investigating thousands of students with the aim of discrediting their activism and destroying their career prospects. After a Senate committee led by Frank Church exposed this practice, the FBI disavowed it and applied a heightened standard for initiating investigations at universities. There is reason to believe, however, that federal law enforcement is facing pressure to relax its self-restraint and investigate pro-Palestinian student activists using a tool not at its disposal in the heyday of COINTELPRO: a nebulous federal statute that imposes prison sentences of up to twenty years for providing "material support or resources to a foreign terrorist organization." This statute criminalizes public advocacy that is done under the direction of or in coordination with foreign terrorist groups. There are few legal constraints, however, that would prevent a motivated FBI from using pro-Palestinian speech as grounds for investigating students who have no connection to such a group.
Alban Berg’s contribution to the Adolf Loos Festschrift : A New Translation
Authors: Lawler Daniel
Published: June 2024

Abstract: Aban Berg’s poem on the occasion of Adolf Loos’s sixtieth birthday has been translated numerous times. None of these translations, however, captures the form of the poem, rather than the content, which in this case is the key to understanding the work’s meaning. An introduction elaborates these ideas, followed by a new translation incorporating them.
Inactivation of an Indonesian isolate of foot-and-mouth disease virus using formaldehyde
Authors: Tobing Talenta Miracle , Rantam Fedik Abdul , Widiyatno Thomas Valentinus , Tacharina Martia Rani , Rahmahani Jola , Triakoso Nusdianto , Kuncorojakti Suryo , Puspitasari Heni , Susilowati Helen , Diyantoro Diyantoro , Azzahra Fadia , Kurniawan Yudha , Aswin Ahmad , Susila Edy Budi
Published: June 2024

Background and Aim: Foot-and-mouth disease (FMD) is a highly contagious viral disease that endangers livestock and the environment with significant economic consequences. This study aimed to validate the inactivation of the Indonesian isolate of foot-and-mouth disease virus (FMDV) with various formaldehyde concentration.

Materials and Methods: The experiment started with FMDV being adapted on BHK-21 cells until cytopathic effects (CPE) appeared. The biological titer of the virus was determined using the 50% tissue culture infectious dose (TCID50) assay. The virus was inactivated by exposing the isolate to different formaldehyde (FA) concentrations (0.025%, 0.05%, 0.1%, and 0.2%) at 37°C for 24 h, and residual infectivity was assessed using CPE scoring of reinoculated BHK-21 cells.

Results: 72 h post-inoculation, the virulence of the FMDV isolate was indicated by complete CPE on BHK-21 monolayer cells, with a TCID50 value of 109/mL; CPE scoring did not signify significant differences (p < 0.05) among 0.025%, 0.05%, 0.1%, 0.2% FA, and the negative control. All treatment groups showed significant differences (p < 0.05) from the positive control (C+). FA concentrations inactivated the FMDV isolate under the given conditions. 0.025% and 0.05% FA continued to display CPE through the third passage, while 0.2% FA did not significantly differ from 0.1% FA (p > 0.05). 0.1% FA is the optimal concentration for safely and effectively inactivating FMDV.

Conclusion: All of the formaldehyde concentrations can completely inactivate the FMDV isolate, with the most optimal and safe concentration being 0.1%.

Keywords: foot-and-mouth disease virus, formaldehyde inactivation, vaccine development.
Evaluation of early African swine fever virus detection using CP204L gene encoding the p30 protein using quantitative polymerase chain reaction
Authors: Tram Ngo Thi Ngoc , Lai Danh Cong , Dung Do Thi Phuong , Toan Nguyen Tat , Duy Do Tien
Published: June 2024

Background and Aim: The African swine fever virus (ASFV), spanning 170–193 kb, contains over 200 proteins, including p72 and p30, which play crucial roles in the virus’s entry and expression. This study investigated the capability of detecting ASFV early through the analysis of genes B646L and CP204L, encoding p72 and p30 antigen proteins, by employing ASFV, diagnosis, immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR), and IHC techniques.

Materials and Methods: Samples were taken from both experimentally and field-infected pigs to evaluate the effectiveness of qPCR and IHC in detecting ASFV. Twenty-two infected pigs were necropsied at 3-, 5-, 7-, and 9-day post-infection to obtain the first set of samples, collecting anticoagulated blood and tissues each time. The thymus, spleen, and lymph nodes were processed by fixing in 10% formalin, paraffin-blocking, and undergoing IHC staining. Forty anticoagulated blood samples were collected from clinically infected sows at a pig farm for the second batch of samples. Based on the lowest Ct values, three blood samples were diluted fivefold for qPCR DNA testing, and their tissues were used for both qPCR and IHC analyses.

Results: At 1-day post-infection, p30-qPCR identified more ASFV-positive pigs and measured lower Ct values compared to p72-qPCR. At later time points, both methods showed similar levels of detection. ASFV was detected earlier and with lower Ct values in lymphoid tissues using p30-qPCR compared to p72-qPCR, particularly in the spleen and lymph nodes. In a field outbreak study, p30-qPCR demonstrated superior sensitivity and lower Ct values when detecting ASFV in blood samples compared to p72-qPCR.

Conclusion: The early detection of the CP204L gene encoding p30 and its corresponding antigenic protein in ASFV diagnosis compared to the gene encoding p72 suggests that CP204L and p30 are promising candidates for the development of more effective antigen and antibody testing methods.

Keywords: African swine fever virus, diagnosis, immunohistochemistry, quantitative polymerase chain reaction.