bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intralesional administration of L19IL2/L19TNF in high-risk locally advanced basal cell carcinoma or cutaneous squamous cell carcinoma.
Authors: Flatz Lukas , Leiter Ulrike M. , Meraz Torres Francisco , Wolfsperger Frederik Carlos , Meiwes Andreas , Wagner Nikolaus , Nadal Lisa , Puca Emanuele , Durak Derya , Covelli Alfredo , Elia Giuliano , Cozzio Antonio , Neri Dario , Amaral Teresa 
Published: June 2024

TPS9617 Background: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) account for 99% of skin neoplasms, with a rising incidence due to increased sun exposure and growing life expectancy. Approximately 0.8-5% of patients (pts) develop high-risk locally advanced (LA) disease, which is treated with surgery, radiotherapy, sonic hedgehog inhibitors, PD1-based immune checkpoint blockade, or chemotherapy. While surgery offers high cure rates, factors such as location, functional and cosmetic impairment, or patient factors including age, comorbidities, and personal preferences may preclude surgery. Intralesional treatment with immunostimulatory drugs represents an attractive therapeutic approach to treat LA BCC and LA cSCC. Here, we investigate a combination of two immunocytokines (Bifikafusp alfa (L19IL2) and Onfekafusp alfa (L19TNF)) targeting the extradomain B of fibronectin (EDB) for the treatment of high-risk locally advanced BCC and cSCC. EDB is an oncofetal antigen that is undetectable in virtually all healthy adult tissues but becomes highly expressed in tumors, including BCC and cSCC. Methods: In a single-arm phase II study (NCT04362722), pts with locally advanced, non-metastatic, node-negative, single, or multifocal BCC or cSCC not eligible for surgery or radiotherapy are treated with four weekly intratumoral administrations of L19IL2/L19TNF. The study is divided into two parts: a first exploratory part with a total of 40 pts with laBCC or lacSCC, and a second part where the laBCC cohort has been expanded to up to 72 pts not eligible for surgery or radiotherapy. The first part of the trial has been completed with 28 laBCC pts and 12 lacSCC pts evaluable for safety and efficacy. The pre-specified activity goal for the first stage of accrual was met, and the second stage of accrual began in September 2023, with a total of 39 BCC and 18 cSCC pts enrolled so far. Clinical trial information: NCT04362722 .
Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates
Authors: Satyal Uttam , Valentine Henkel , Liu David , Slifker Michael , Lallas Costas D. , Trabulsi Edouard J. , Bukavina Laura , Szeto Lauren , Hoffman-Censits Jean H. , Mouw Kent W. , Faltas Bishoy M. , Grivas Petros , Ibragimova Ilsiya , Porten Sima P. , Van Allen Eliezer M. , Geynisman Daniel M. , Parker Daniel C. , O'Neill John P. , Drevik Johnathan , Christianson Sarah S. , Ginzburg Serge , Correa Andres F. , Uzzo Robert G. , Ross Eric A. , Zibelman Matthew R. , Ghatalia Pooja , Plimack Elizabeth R. , Kutikov Alexander , Abbosh Philip H. 
Published: June 2024

PURPOSE There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing–based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662 , n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732 ). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.
Synthetic Lethality Beyond BRCA: A Phase I Study of Rucaparib and Irinotecan in Metastatic Solid Tumors With Homologous Recombination-Deficiency Mutations Beyond BRCA1/2
Authors: Tsang Erica S. , Dhawan Mallika S. , Pacaud Romain , Thomas Scott , Grabowsky Jennifer , Wilch Lauren , Karipineni Silpa , Kelley Robin Kate , Ko Andrew H. , Collisson Eric , Chapman Jocelyn S. , Ueda Stefanie , Bergsland Emily K. , Munster Pamela 
Published: June 2024

PURPOSE Combining poly ADP-ribose polymerase (PARP) and topoisomerase I inhibitors has demonstrated synergistic effects in in vivo models. This phase I trial evaluated rucaparib and irinotecan in metastatic solid tumors with homologous recombination deficiency. METHODS This study enrolled patients in three cohorts to determine the tolerability and preliminary efficacy of (1) rucaparib 400 mg PO twice a day (days 1-7, 15-21) and irinotecan 65 mg/m2 intravenously once every 2 weeks; (2) rucaparib 400 mg PO twice a day (D1-7, 15-21) and irinotecan 100 mg/m2 once every 2 weeks; and (3) rucaparib 400 mg per os twice a day (D1-7) and irinotecan 100 mg/m2 once every 3 weeks. RESULTS Twenty patients were enrolled: 95% with previous platinum, 40% with previous irinotecan, and 20% with previous PARP inhibitor. The maximally tolerated was determined as rucaparib 400 mg twice a day days 1-7 and irinotecan 100 mg/m2 once every 3 weeks. Four dose-limiting toxicities (all grade 3-4 neutropenia) occurred during dose escalation with only neutropenia as other grade 3-4 toxicities (25%; grade 3 [n = 3], grade 4 [n = 2]). Treatment-related grade 1-2 adverse events included neutropenia (45%), diarrhea (45%), nausea (40%), and fatigue (30%). Of 17 patients with evaluable disease, six patients (35%) derived clinical benefit (n = 2 with PR, n = 4 with stable disease for over 6 months). Three patients remained on study >1 year: two with ATM mutations (small bowel carcinoma and pancreatic neuroendocrine tumor) and one patient with a PALB2 mutation (primary peritoneal cancer). CONCLUSION Pulse dosing of rucaparib and once every 3 weeks irinotecan was well tolerated for up to 18 months with durable responses in BRCA-, PALB2-, and ATM-mutated cancers despite progression on previous platinum.
Talazoparib in Patients With Solid Tumors With BRCA1/2 Mutation: Results From the Targeted Agent and Profiling Utilization Registry Study
Authors: Srkalovic Gordan , Rothe Michael , Mangat Pam K. , Garrett-Mayer Elizabeth , Ahn Eugene R. , Brouse Gregory , Chan John , Mehmi Inderjit , Khalil Maya , Duvivier Herbert L. , Gaba Anu , Leuva Harshraj , Thota Ramya , Yost Kathleen J. , Grantham Gina N. , Gregory Abigail , Hinshaw Dominique C. , Halabi Susan , Schilsky Richard L. 
Published: June 2024

PURPOSE The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1/2 mutations treated with talazoparib are reported. METHODS Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Patients with germline BRCA-mutated human epidermal growth factor receptor 2–negative locally advanced or metastatic breast cancer were not eligible for this study. Primary end point was disease control (DC) determined by investigator assessment of objective response (OR) or stable disease (SD) of at least 16 weeks duration (SD16+). The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = 0.82; α = .10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety. RESULTS Twenty-eight patients (20 cancer types) with BRCA1/2 mutations were enrolled from December 2019 to September 2021 and collapsed into a single histology pooled cohort for analysis. All patients were evaluable for efficacy. One complete response, nine partial response, and six SD16+ were observed for DC and OR rates of 57% (one-sided 90% CI, 43 to 100) and 36% (95% CI, 19 to 56), respectively. The null hypothesis of a 15% DC rate was rejected ( P < .001). Patients with OR had the following tumor types: breast (2), nonmelanoma skin, mesothelioma, stomach, uterus, non–small cell lung cancer, ovary, hepatocellular carcinoma, and pancreas. Thirteen patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to talazoparib. All were consistent with the drug label except bilirubin increase and hyponatremia (both grade 3 AEs). CONCLUSION Talazoparib demonstrated antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations, including cancer types for which poly ADP-ribose polymerase inhibitors are not yet US Food and Drug Administration–approved.
Tropical Skins
Authors: Levin Ayala 
Published: June 2024

Abstract
This essay is concerned with how architecture was imagined to mediate tropical climate in the interest of forming productive postcolonial national subjects. It charts a transition in approach from late colonial to postcolonial modernist architecture as it was exemplified in the design of the University of Ife campus in Nigeria in the 1960s by an Israeli team led by Arieh Sharon in collaboration with the Department of Landscape Architecture at the University of Wisconsin–Madison. Sharon's team formed an alternative to the postwar predominance of sun-shading devices, specifically as the British colonial architects Maxwell Fry and Jane Drew employed them in their design of the neighboring University College Ibadan campus. The essay considers the midcentury discourse on sun-shading devices in relation to the contemporaneous theory of “human capital” and demonstrates how this discourse drew from the eighteenth-century notion of architectural “character,” which links the productive capacities of different races with architectural representation.
Confinement promotes nematic alignment of spindle-shaped cells during Drosophila embryogenesis
Authors: Ray Tirthankar , Shi Damo , Harris Tony J. C. 
Published: June 2024

ABSTRACT
Tissue morphogenesis is often controlled by actomyosin networks pulling on adherens junctions (AJs), but junctional myosin levels vary. At an extreme, the Drosophila embryo amnioserosa forms a horseshoe-shaped strip of aligned, spindle-shaped cells lacking junctional myosin. What are the bases of amnioserosal cell interactions and alignment? Compared with surrounding tissue, we find that amnioserosal AJ continuity has lesser dependence on α-catenin, the mediator of AJ-actomyosin association, and greater dependence on Bazooka/Par-3, a junction-associated scaffold protein. Microtubule bundles also run along amnioserosal AJs and support their long-range curvilinearity. Amnioserosal confinement is apparent from partial overlap of its spindle-shaped cells, its outward bulging from surrounding tissue and from compressive stress detected within the amnioserosa. Genetic manipulations that alter amnioserosal confinement by surrounding tissue also result in amnioserosal cells losing alignment and gaining topological defects characteristic of nematically ordered systems. With Bazooka depletion, confinement by surrounding tissue appears to be relatively normal and amnioserosal cells align despite their AJ fragmentation. Overall, the fully elongated amnioserosa appears to form through tissue-autonomous generation of spindle-shaped cells that nematically align in response to confinement by surrounding tissue.
High-efficiency three-port beam splitter under normal incidence
Authors: Li Xingxue , Xu Mengqing , Liao Jiajing , Yang Xiufan , Zhou Changhe , Jia Wei , Wang Jin , Xie Yongfang 
Published: June 2024

A fused-silica three-port grating under TE-polarized normal incidence
is designed and manufactured with improved diffraction efficiency (DE)
and bandwidth. A physical explanation of the grating diffraction is
provided using the simplified mode method (SMM), and parameters of the
grating structure were optimized using rigorous coupled-wave analysis
(RCWA). For a given set of optimized parameters, a transmitted
three-port grating with an area of 170mm×170mm was fabricated by scanning beam
interference lithography (SBIL), and diffraction properties were
investigated. The average DEs for the +1, 0, and 1 orders of the 25 sampling
points are 29%, 30%, and 31% at a 632.8 nm incident wavelength.
Additionally, the measured DEs of the +1, 0, and 1 orders all exceed 25% at
the wavelength range from 613 to 653 nm.
The frequency and associated factors of typhoid carriage in patients undergoing cholecystectomy for gallbladder disease in Pakistan: A cross-sectional study
Authors: Qureshi Sonia , Maria Noshi , Chawla Tabish , Iqbal Junaid , Kazi Abdul Momin , Adnan Mehreen , Hotwani Aneeta , Rahman Najeeb , Sadiq Muhammed Wahhaab , Charles Richelle , Baker Stephen , Qamar Farah Naz 
Published: June 2024

Background
Enteric fever is caused by Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi A, B, and C. It continues to be a significant cause of morbidity and mortality worldwide. In highly endemic areas, children are disproportionately affected, and antimicrobial resistance reduces therapeutic options. It is estimated that 2–5% of enteric fever patients develop chronic asymptomatic infection. These carriers may act as reservoirs of infection; therefore, the prospective identification and treatment of carriers are critical for long-term disease control. We aimed to find the frequency of Salmonella Typhi carriers in patients undergoing cholecystectomy. We also compared the detection limit of culturing versus qPCR in detecting S. Typhi, performed a geospatial analysis of the carriers identified using this study, and evaluated the accuracy of anti-Vi and anti-YncE in identifying chronic typhoid carriage.

Methods
We performed a cross-sectional study in two centers in Pakistan. Gallbladder specimens were subjected to quantitative PCR (qPCR) and serum samples were analyzed for IgG against YncE and Vi by ELISA. We also mapped the residential location of those with a positive qPCR result.

Findings
Out of 988 participants, 3.4% had qPCR-positive gallbladder samples (23 S. Typhi and 11 S. Paratyphi). Gallstones were more likely to be qPCR positive than bile and gallbladder tissue. Anti-Vi and YncE were significantly correlated (r = 0.78 p<0.0001) and elevated among carriers as compared to qPCR negative controls, except for anti-Vi response in Paratyphi A. But the discriminatory values of these antigens in identifying carriers from qPCR negative controls were low.

Conclusion
The high prevalence of typhoid carriers observed in this study suggests that further studies are required to gain information that will help in controlling future typhoid outbreaks in a superior manner than they are currently being managed.
Evaluation of transmission-blocking potential of PvPSOP25 using transgenic murine malaria parasite and clinical isolates
Authors: Zhang Biying , Feng Hao , Zhao Yan , Zhang Di , Yu Xinxin , Li Yusi , Zeng Ying , Thongpoon Sataporn , Roobsoong Wanlapa , Wu Yudi , Liu Fei , Sattabongkot Jetsumon , Min Hui , Cui Liwang , Cao Yaming 
Published: June 2024

Background
Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The putative-secreted ookinete protein 25 (PSOP25), highly conserved in Plasmodium spp., is a promising TBV target. Here, we investigated PvPSOP25 from P. vivax as a TBV candidate using transgenic murine parasite P. berghei and clinical P. vivax isolates.

Methods and findings
A transgenic P. berghei line expressing PvPSOP25 (TrPvPSOP25Pb) was generated. Full-length PvPSOP25 was expressed in the yeast Pichia pastoris and used to immunize mice to obtain anti-rPvPSOP25 sera. The transmission-blocking activity of the anti-rPvPSOP25 sera was evaluated through in vitro assays and mosquito-feeding experiments. The antisera generated by immunization with rPvPSOP25 specifically recognized the native PvPSOP25 antigen expressed in TrPvPSOP25Pb ookinetes. In vitro assays showed that the immune sera significantly inhibited exflagellation and ookinete formation of the TrPvPSOP25Pb parasite. Mosquitoes feeding on mice infected with the transgenic parasite and passively transferred with the anti-rPvPSOP25 sera showed a 70.7% reduction in oocyst density compared to the control group. In a direct membrane feeding assay conducted with five clinical P. vivax isolates, the mouse anti-rPvPSOP25 antibodies significantly reduced the oocyst density while showing a negligible influence on mosquito infection prevalence.

Conclusions
This study supported the feasibility of transgenic murine malaria parasites expressing P. vivax antigens as a useful tool for evaluating P. vivax TBV candidates. Meanwhile, the moderate transmission-reducing activity of the generated anti-rPvPSOP25 sera necessitates further research to optimize its efficacy.
Randomized trial to compare acceptability of magnesium sulphate administration for preeclampsia and eclampsia: Springfusor pump versus standard of care
Authors: Ononge Sam , Nakimuli Annettee , Byamugisha Josaphat , Adroma Moses , Kiondo Paul , Easterling Thomas , Bracken Hillary 
Published: June 2024

Introduction
In low-resource settings, magnesium sulphate (MgSO4) for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation, and reduced compliance.

Objective
To determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia.

Design
Randomized Open Label Clinical Trial.

Methods
The study was conducted at Kawempe National Referral Hospital. Eligible women had a systolic blood pressure of ≥140mmHg and or diastolic blood pressure >90mmHg, proteinuria ≥+1, and the physician’s decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to a Springfusor® pump group (n = 248) or control (standard of care) (n = 248) administration of MgSO4. Intervention group had a loading dose (4gm of 50% MgSO4 intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4 intravenously per hour for 24 hours) administered using the Springfusor®. The standard of care (SOC) group received a loading dose of 4gm of 20% MgSO4 IV over 15–20 minutes, followed by 10gm of 50% MgSO4 intramuscular (5gm in each buttock) and a maintenance dose of 5gm of 50% MgSO4 was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines. Acceptability of the method of administration was assessed using a Likert scale (1–5; 1 and 2: acceptable and 3–5: unacceptable). Pain at the site of MgSO4 administration was assessed using a Visual Analogue Scale 1–7, (1 minimal pain and 7 worst pain). Comparisons were assessed with the Chi-square test, Mann Whitney-Wilcoxon test, and Students’ t-test.

Results
Intervention arm; was more acceptable than the standard of care arm, (95.3% vs70.3%; p<0.001), had a lower median pain score, (2(CI: 2–2), vs 4(CI: 4–5) p<0.001), and fewer side effects. Maternal mortality was comparable between groups (0.8% in the intervention arm vs 1.2% in the IM arm).

Trial registration
Trial No PACTR201712002887266 (https://pactr.samrc.ac.za/).
Effect of core strength training on the badminton player’s performance: A systematic review & meta-analysis
Authors: Ma Shuzhen , Soh Kim Geok , Japar Salimah Binti , Liu Chunqing , Luo Shengyao , Mai Yiqiang , Wang Xinzhi , Zhai Mengze 
Published: June 2024

BackgroundCore strength training (CST) has been shown to improve performance in several sports disciplines. CST is recognized as one of the crucial elements that enhance athletic performance, particularly impacting badminton skills. Despite its popularity as a strength training method among badminton players, there is a lack of comprehensive studies examining the effectiveness of CST on the performance of these athletes.ObjectiveThis study aims to ascertain CST’s effects on badminton players’ performance.MethodThis study followed PRISMA principles and conducted comprehensive searches in well-known academic databases (SCOPUS, Pubmed, CNKI, Web of Science, Core Collection, and EBSCOhost) up to August 2023. The inclusive criteria were established using the PICOS framework. Following their inclusion based on PICOS criteria, the selected studies underwent literature review and meta-analysis. The methodological quality of the assessments was evaluated using Cochrane Collaboration’s risk of bias tools bias risk tools and recommendations for a graded assessment, development, and evaluation.ResultsThe analysis included participants aged 10–19 years from 13 studies of moderate quality, totaling 208 individuals. The CST intervention s lasted between 4 to 16 weeks, with a frequency of 1 to 4 sessions per week and each session lasting 20 to 120 minutes. Sample sizes across these studies ranged from 8 to 34 participants. According to the meta-analysis, CST significantly influenced badminton performance, particularly in areas of explosive power (ES = 0.03 P = 0.04), front-court skill (ES = 2.53, P = 0.003), and back-court skill (ES = 2.33, P = 0.002).ConclusionCST enhances badminton players’ fitness (strength, power, balance, and stability), in situ (front/back-court) skills, and movement position hitting. However, its effects on speed, endurance, agility, flexibility, and coordination are unclear, revealing a research gap. The precise benefits of CST, especially on flexibility and specific hitting skills (smashes, clears, drives, net shots, crosscourt, push, and lift shots), need more investigation. Additionally, research on CST’s impact on female athletes is significantly lacking.
Die Ambiguität des Geistes
Authors: Hansen Bjarke Mørkøre Stigel 
Published: June 2024

Abstract
This article explores both the significance and difficulty of the work of Paul Valéry (1871–1945), arguing that his challenging ideas on Europe and its crisis have much to contribute to recent debates on the philosophy of Europe. For Valéry, Europe is inseparable from its (spiritual) history, caught up in the process of self-understanding and self-alienation. In order to examine this process, the article focuses on Valéry’s tripartite composition of Europe’s “influences,” namely the institutions and laws of the Roman Empire, the self-examination of Christianity, and the discipline of spirit and development of science in ancient Greek culture.