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Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8

BACKGROUND: Anaplastic thyroid cancer is a rare and aggressive cancer with no standard radiotherapy-based local treatment. Based on data suggesting synergy between pazopanib and paclitaxel in anaplastic thyroid cancer, NRG Oncology did a double-blind, placebo-controlled, randomised phase 2 clinical trial comparing concurrent paclitaxel and intensity-modulated radiotherapy (IMRT) with the addition of pazopanib or placebo with the aim of improving overall survival in this patient population. METHODS: Eligible patients were aged 18 years or older with a pathological diagnosis of anaplastic thyroid cancer, any TNM stage, Zubrod performance status of 0-2, no recent haemoptysis or bleeding, and no brain metastases. Patients were enrolled from 34 centres in the USA. Initially, a run-in was done to establish safety. In the randomised phase 2 trial, patients in the experimental group (pazopanib) received 2-3 weeks of weekly paclitaxel (80 mg/m2) intravenously and daily pazopanib suspension 400 mg orally followed by concurrent weekly paclitaxel (50 mg/m2), daily pazopanib (300 mg), and IMRT 66 Gy given in 33 daily fractions (2 Gy fractions). In the control group (placebo), pazopanib was replaced by matching placebo. Patients were randomly assigned (1:1) to the two treatment groups by permuted block randomisation by NRG Oncology with stratification by metastatic disease. All investigators, patients, and funders of the study were masked to group allocation. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with Clinicaltrials.gov, NCT01236547, and is complete. FINDINGS: The safety run-showed the final dosing regimen to be safe based on two out of nine participants having adverse events of predefined concern. Between June 23, 2014, and Dec 30, 2016, 89 patients were enrolled to the phase 2 trial, of whom 71 were eligible (36 in the pazopanib group and 35 in the placebo group; 34 [48%] males and 37 [52%] females). At the final analysis (data cutoff March 9, 2020), with a median follow-up of 2·9 years (IQR 0·002-4·0), 61 patients had died. Overall survival was not significantly improved with pazopanib versus placebo, with a median overall survival of 5·7 months (95% CI 4·0-12·8) in the pazopanib group versus 7·3 months (4·3-10·6) in the placebo group (hazard ratio 0·86, 95% CI 0·52-1·43; one-sided log-rank p=0·28). 1-year overall survival was 37·1% (95% CI 21·1-53·2) in the pazopanib group and 29·0% (13·2-44·8) in the placebo group. The incidence of grade 3-5 adverse events did not differ significantly between the treatment groups (pazopanib 88·9% [32 of 36 patients] and placebo 85·3% [29 of 34 patients]; p=0·73). The most common clinically significant grade 3-4 adverse events in the 70 eligible treated patients (36 in the pazopanib group and 34 in the placebo group) were dysphagia (13 [36%] vs 10 [29%]), radiation dermatitis (8 [22%] vs 13 [38%]), increased alanine aminotransferase (12 [33%] vs none), increased aspartate aminotransferase (eight [22%] vs none), and oral mucositis (five [14%] vs eight [24%]). Treatment-related serious adverse events were reported for 16 (44%) patients on pazopanib and 12 (35%) patients on placebo. The most common serious adverse events were dehydration and thromboembolic event (three [8%] each) in patients on pazopanib and oral mucositis (three [8%]) in those on placebo. There was one treatment-related death in each group (sepsis in the pazopanib group and pneumonitis in the placebo group). INTERPRETATION: To our knowledge, this study is the largest randomised anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter NCI National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated. FUNDING: National Cancer Institute and Novartis.

Periodic micro/nanoscale structures from nature have inspired the scientific community to adopt surface design for various applications, including superhydrophobic drag reduction. One primary concern of practical applications of such periodic microstructures remains the scalability of conventional microfabrication technologies. This study demonstrates a simple template-free scalable manufacturing technique to fabricate periodic microstructures by controlling the ribbing defects in the forward roll coating. Viscoelastic composite coating materials are designed for roll-coating using carbon nanotubes (CNT) and polydimethylsiloxane (PDMS), which helps achieve a controllable ribbing with a periodicity of 114–700 µm. Depending on the process parameters, the patterned microstructures transition from the linear alignment to a random structure. The periodic microstructure enables hydrophobicity as the water contact angles of the samples ranged from 128° to 158°. When towed in a static water pool, a model boat coated with the microstructure film shows 7%–8% faster speed than the boat with a flat PDMS film. The CNT addition shows both mechanical and electrical properties improvement. In a mechanical scratch test, the cohesive failure of the CNT-PDMS film occurs in ≈90% higher force than bare PDMS. Moreover, the nonconductive bare PDMS shows sheet resistance of 747.84–22.66 Ω □−1 with 0.5 to 2.5 wt% CNT inclusion.

The article aimed to highlight the varied perceptions of students studying Gender Studies as an academic discipline at Quaid-i-Azam University (QAU), Pakistan. The research objective of this article was to document the students' experiences, perceptions, misconceptions, and anxieties regarding Gender Studies. This research is the result of a continuous journey in this field where we have actively engaged and interacted with students studying in various semesters. The research was qualitative in nature and in-depth interview guidelines were employed to conduct interviews with the students of the Center of Excellence in Gender Studies (CEGS) at QAU, Islamabad. The sample size consisted of 20 students who hailed from different geographical areas of Pakistan and belonged to diverse socio-cultural and economic backgrounds. Additionally, the sample was purposely selected to include only students in their final semester. The study revealed that the instructors teaching Gender Studies were accused of propagating Western theories, and this had become a cause of concern and provocation for many students. A large number of students have indicated that they were unaware or ignorant of this academic discipline and were familiarized only after securing admission based on merit. The research demonstrates that these students were unsure of the scope of the subject and the employment opportunities it offered upon completion of their degree in Gender Studies. The respondents were under the impression that this academic discipline is not only antagonistic to their Pakistani culture but also promotes a Western agenda. A few respondents shared their experiences and pointed out that feminism faces a strong backlash in Pakistani society; hence, they found it difficult to see the relevance of feminism in Pakistan. The research also revealed that studying the discipline of Gender Studies has helped the respondents to introspect, deconstruct, and criticize their preconceived notions about gender and women. While Gender Studies as an academic discipline has equipped the students to deal with gender-based issues, it has also stirred arguments with their families. Lastly, Gender Studies created awareness related to gender issues and helped the students to overcome their misconceptions. Keywords: Gender Studies, Student perceptions, Pakistan, Higher education, Introduction Women's Studies and Gender Studies not only challenge traditional knowledge imparted by the mainstream social sciences (Sociology, Anthropology, Political Science, and International Relations), but these disciplines also aim to [...]

BackgroundMatrix metalloproteinase 9 (MMP9) expression in the tumor microenvironment is implicated in multiple protumorigenic processes. Andecaliximab (GS-5745), a monoclonal antibody targeting MMP9 with high affinity and selectivity, was evaluated in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma.Patients and methodsThis phase I study was completed in two parts: part A was a dose-finding, monotherapy phase that enrolled patients with advanced solid tumors, and part B examined andecaliximab in combination with chemotherapy in specific patient cohorts. In the cohort of patients with pancreatic adenocarcinoma (n = 36), andecaliximab 800 mg every 2 weeks was administered in combination with gemcitabine and nab-paclitaxel. Patients were treated until unacceptable toxicity, withdrawal of consent, disease progression, or death. Efficacy, safety, and biomarker assessments were performed.ResultsAndecaliximab combined with gemcitabine and nab-paclitaxel appeared to be well tolerated and did not demonstrate any unusual toxicities in patients with pancreatic adenocarcinoma. The most common treatment-emergent adverse events were fatigue (75.0%), alopecia (55.6%), peripheral edema (55.6%), and nausea (50.0%). Median progression-free survival was 7.8 months (90% confidence interval, 6.9-11.0) with an objective response rate of 44.4% and median duration of response of 7.6 months. Maximal andecaliximab target binding, defined as undetectable, andecaliximab-free MMP9 in plasma, was observed.ConclusionAndecaliximab in combination with gemcitabine and nab-paclitaxel demonstrates a favorable safety profile and clinical activity in patients with advanced pancreatic adenocarcinoma.Implications for practiceThe combination of andecaliximab, a novel, first-in-class inhibitor of matrix metalloproteinase 9, with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma provided a median progression-free survival of 7.8 months and objective response rate of 44.4%. The majority of systemic biomarkers related to matrix metalloproteinase 9 activity and immune suppression increased at 2 months, whereas biomarkers related to tumor burden decreased. Although this study demonstrates promising results with andecaliximab plus chemotherapy in patients with advanced pancreatic adenocarcinoma, andecaliximab was not associated with a survival benefit in a phase III study in patients with advanced gastric/gastroesophageal junction carcinoma.