bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovering API usage specifications for security detection using two-stage code mining
Authors: Yin Zhongxu , Song Yiran , Zong Guoxiao
Published: October 2024

An application programming interface (API) usage specification, which includes the conditions, calling sequences, and semantic relationships of the API, is important for verifying its correct usage, which is in turn critical for ensuring the security and availability of the target program. However, existing techniques either mine the co-occurring relationships of multiple APIs without considering their semantic relationships, or they use data flow and control flow information to extract semantic beliefs on API pairs but difficult to incorporate when mining specifications for multiple APIs. Hence, we propose an API specification mining approach that efficiently extracts a relatively complete list of the API combinations and semantic relationships between APIs. This approach analyzes a target program in two stages. The first stage uses frequent API set mining based on frequent common API identification and filtration to extract the maximal set of frequent context-sensitive API sequences. In the second stage, the API relationship graph is constructed using three semantic relationships extracted from the symbolic path information, and the specifications containing semantic relationships for multiple APIs are mined. The experimental results on six popular open-source code bases of different scales show that the proposed two-stage approach not only yields better results than existing typical approaches, but also can effectively discover the specifications along with the semantic relationships for multiple APIs. Instance analysis shows that the analysis of security-related API call violations can assist in the cause analysis and patch of software vulnerabilities.
The Egyptian 24-h movement guidelines for children and adolescents: an integration of physical activity, sedentary behaviour, sleep and eating habits—by the Egyptian Academy of Bone and Muscle health
Authors: El Miedany Y. , Lotfy Hala , Hegazy Laila A.G. , Elgaafary Maha , Mahran Safaa , Plummer Susan , Elwakil Walaa
Published: October 2024

Background

The objectives of this work were as follows: (1) to develop holistic recommendations for physical activity, sleep, sedentary behaviours and eating habits adapted to children and adolescent life stage (5–17 years) and targeting optimal metabolic cycle and achieving energy balance; (2) to provide evidence-based information that can be used by the government, policy makers, healthcare professionals, community, schools as well as families to endorse active, healthy, living in apparently healthy children and youth aged 5–17 years, and as a base for monitoring the activities, particularly the physical ones, on the people level. The Egyptian Academy of Bone and Muscle Health followed an established guideline development process to create the Egyptian 24-h movement clinical guideline for children and adolescents. Online databases (PubMed, Embase and Cochrane Library) were searched for relevant peer-reviewed studies that met the a priori inclusion criteria.

Results

A total of 41 studies met the inclusion criteria. Leveraging evidence from the review of the literature led to the development of 11 key questions covering 8 domains. Fifteen statements focus on the overall identified targets through integration of the movement activities and eating behaviour. Results revealed a major change in the previous basic understandings as it shifts away from segregated into integrated movement behaviour and dietary habit paradigm. Based on this, the final guideline was developed providing evidence-based recommendations for a “Healthy 24-h day”, for Egyptian children and adolescents.

Conclusion

The 24-h composition of movement behaviours has principal implications for health at all ages. The developed guideline provides an up-to-date evidence-based recommendation towards a holistic approach for favourable daily life activities and adopts a feasible perspective by outlining these activities within a 24-h period. In addition, eating and dietary elements have been included to complete the energy cycle. Children and adolescents who meet the 24-h movement guidelines generally report more favourable health indicators than those who do not.
Gene expression profile comparison of primary and pulmonary metastatic lesions in a dog with appendicular osteosarcoma and hypertrophic osteopathy
Authors: Kitagawa Keita , Dryfhout Jessica , Engleberg Alexander I. , Yang Ya-Ting , Yuzbasiyan-Gurkan Vilma , Vilar-Saavedra Paulo
Published: October 2024

Hypertrophic osteopathy (HO) is a paraneoplastic syndrome, and the most notable cause in dogs is pulmonary metastatic osteosarcoma (OSA). Although many molecular factors in canine OSA have been shown in metastasis, little is known about the gene expression profile of HO secondary to metastatic OSA. Therefore, the purpose of this study was to compare the gene expression profiles between primary and metastatic OSA lesions from the same dog and to look for gene expression changes that can elucidate the molecular mechanism of metastases and HO. Tumoral samples were obtained from a 2-year-old, intact male, Labrador retriever. At the first visit, the patient presented with an appendicular OSA as the primary lesion. About 10 months later, the dog developed HO due to a single pulmonary metastasis. Using these primary and metastatic samples from the same dog, as well as normal canine osteoblasts, we investigated the gene expression profiling using the NanoString nCounter® Canine IO panel. A total of 180 differentially expressed genes were identified between malignant OSA cells and non-malignant canine osteoblasts. Furthermore, 5 genes (CCL17, VEGFC, C3, C4BPA, and FOS) were differentially expressed in comparison between primary and metastatic OSA samples. CCL17 and VEGFC were upregulated in the primary lesion compared to the metastatic lesion, while C3, C4BPA, and FOS were downregulated in the primary lesion relative to the metastatic lesion. Given that the metastatic lesion was relevant to the development of HO, the different gene expression profiles may be relevant to understanding the pathophysiology of HO.
Understanding the medication regimens associated with anticholinergic burden in older people's mental health services in the UK
Authors: Barnes Thomas R. E. , Bishara Delia , Burns Alistair , Myint Phyo K. , Rendora Olivia , Edokpolor Pernia Elena M. , Paton Carol
Published: October 2024

Background

Medications with anticholinergic properties are associated with a range of adverse effects that tend to be worse in older people.

Aims

To investigate medication regimens with high anticholinergic burden, prescribed for older adults under the care of mental health services.

Method

Clinical audit of prescribing practice, using a standardised data collection tool.

Results

Fifty-seven trusts/healthcare organisations submitted data on medicines prescribed for 7915 patients: two-thirds (66%) were prescribed medication with anticholinergic properties, while just under a quarter (23%) had a medication regimen with high anticholinergic burden (total score ≥3 on the anticholinergic effect on cognition (AEC) scale). Some 16% of patients with a diagnosis of dementia or mild cognitive impairment were prescribed medication regimens with a high anticholinergic burden, compared with 35% of those without such diagnoses. A high anticholinergic burden was mostly because of combinations of commonly prescribed psychotropic medications, principally antidepressant and antipsychotic medications with individual AEC scores of 1 or 2.

Conclusions

Adults under the care of older people's mental health services are commonly prescribed multiple medications for psychiatric and physical disorders; these medication regimens can have a high anticholinergic burden, often an inadvertent consequence of the co-prescription of medications with modest anticholinergic activity. Prescribers for older adults should assess the anticholinergic burden of medication regimens, assiduously check for adverse anticholinergic effects and consider alternative medications with less anticholinergic effect where indicated. The use of a scale, such as the AEC, which identifies the level of central anticholinergic activity of relevant medications, can be a helpful clinical guide.
A randomized phase II study evaluating concurrent or sequential fixed-dose immune therapy in combination with cisplatin and intensity-modulated radiotherapy in intermediate- or high-risk, previously untreated, locally advanced head and neck cancer (LA SCCHN).
Authors: Clump David Anthony , Zandberg Dan Paul , Skinner Heath Devin , Ohr James , Fenton Moon Jung , Normolle Daniel Paul , Beitler Jonathan Jay , Bauman Julie E. , Ferris Robert L.
Published: October 2024

6007

Background:
Optimal timing, either concurrent or sequential, of anti-programmed death (PD)-1 antibody with chemoradiotherapy (CRT) for LA SCCHN is unknown. Recently, JAVELIN-100 showed no benefit of adding concurrent avelumab to CRT.
Methods:
In this randomized, phase 2 study, patients (pts) with intermediate risk human papillomavirus (HPV) positive oropharyngeal ( > 10 pack years or T4 or N3) or HPV negative previously-untreated LA SCCHN of the oropharynx, hypopharynx, larynx, or oral cavity (unselected PD-L1 status) were randomized 1:1 (stratified by HPV and nodal stage) to receive CRT (cisplatin 40 mg/m
2
weekly + radiation therapy consisting of 70 Gy in 35 fractions and concurrent or sequential pembrolizumab (pembro) 200 mg q 3 week X 8 doses total. Pembro was started 1 week prior to CRT and 2 weeks after CRT in the concurrent and sequential arms respectively. The primary objective was to evaluate two schedules of pembro (concurrent vs. sequential) combined with CRT in order to recommend the regimen to be tested subsequently. The study was powered to detect a signal of antagonism, defined as a 1-year local failure rate exceeding 60% and each arm had to meet all of the following: dose limiting toxicity (DLT) rate £ 20%, 1-year local failure rate (LRF) < 60%, and 1-year PFS ³ 60%. If all three were met the arm with a numerically superior 1-year PFS would be selected for further study. Extensive correlatives were collected and will be reported in the future.
Results:
Between 05/2016 and 05/2021, 80 patients were randomized, 41 participants received concurrent while 39 patients received sequential pembro along with CRT. Minimum follow-up is 9 months with a median > 24 months. Both treatment schedules met the predefined composite endpoints of rate of DLT, LRF, and 1-year PFS. The 1 and 2-year PFS for sequential pembro of 89% was numerically higher than that of 82% and 78% for concurrent pembro. OS at 1 and 2 years was 94% for sequential and 82% and 78% for concurrent pembro. Median PFS and OS was not reached in either arm. 3-year PFS and OS will be reported along with PD-L1 status and other exploratory correlatives. Grade 3 adverse events were 76.7% with concurrent vs 58.9% with sequential pembro added to CRT. There were 2 Grade 5 events with sequential and 3 Grade 5 with concurrent pembro.
Conclusions:
This randomized phase II trial evaluated fixed-dose concurrent versus sequential pembro added to standard CRT in LA SCCHN. Sequential pembro had a numerically superior 1 and 2-year PFS compared to concurrent therapy. Sequential pembro is the preferred regimen to compare with standard of care CRT for LA SCCHN in a phase III trial.
Clinical trial information: NCT02777385.
Effectiveness of adjuvant chemoradiotherapy for oral cavity squamous cell carcinoma with minor and major extranodal extension: A multi-institutional consortium study.
Authors: Manojlovic Kolarski Mirko , Su Jie , Weinreb Ilan , Perez-Ordonez Bayardo , Patel Snehal G. , Valero Cristina , Xu Bin , Katabi Nora , Clark Jonathan , Low Tsu-Hui (Hubert) , Gupta Ruta , Graboyes Evan Michael , Davies Joel C , Richardson Mary , Goldstein David Paul , Huang Shao Hui , O'Sullivan Brian , Xu Wei , Hansen Aaron Richard , de Almeida John R
Published: October 2024

6010

Background:
Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. Recent pathology reporting guidelines recommend stratifying ENE into minor (≤2mm) or major (>2mm) extent. Prior studies have suggested that the addition of chemotherapy to adjuvant radiation may not improve oncologic outcomes in minor ENE. We evaluated this through a large multi-institutional cohort study.
Methods:
Surgically resected primary T1-4,N1-N3,M0 OSCC with pathologic nodal disease treated between 2005-2018 from four institutions in three countries were included. Extent of ENE was re-classified by pathologists on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended as per standard guidelines, unless contraindicated. Uni- (UVA) and Multivariable analysis (MVA) assessed the effect of chemotherapy on survival and disease control in minor and major ENE subgroups. Outcomes were also assessed in propensity score matched cohorts for each subgroup.
Results:
A total of 764 patients were included, of whom 126 (16%) had minor ENE and 242 (32%) had major ENE. Adjuvant chemoradiotherapy was given in 51 (40.5%) with minor ENE and 115 (47.5%) with major ENE. On MVA, chemotherapy was not associated with improved overall survival (OS) (HR 0.97, 95% CI 0.55-1.73, p=0.92) for patients with minor ENE, however, there was significant OS benefit for patients with major ENE (HR 0.61, 95% CI 0.38-0.98, p=0.041) after adjusting for age, T-category, N-category, margin status, adjuvant radiation, LN ratio, LVI, PNI, and ECOG status. Patients with major ENE receiving adjuvant chemoradiotherapy had improved locoregional control (LRC) (HR 0.67, 95% CI 0.42-1.09, p=0.1) although this did not reach statistical significance. Propensity score matched analysis found that patients with minor ENE who did and did not receive chemotherapy had no difference in OS (52% vs. 52%, p=0.85), but those with major ENE did (44% vs 13%, p=0.008).
Conclusions:
In OSCC, the addition of chemotherapy to adjuvant treatment is beneficial in major ENE, but our group failed to demonstrate a benefit for minor ENE. The benefit of chemotherapy in major ENE may result from improved LRC. Minor ENE is a clinically relevant subgroup in OSCC that warrants distinctive adjuvant treatment considerations.
A phase 2 clinical trial of axitinib and avelumab in patients with recurrent/metastatic adenoid cystic carcinoma (ACC).
Authors: Ferrarotto Renata , Bell Diana , Feng Lei , Li Kaiyi , Mott Frank , Blumenschein George R. , Guimaraes de Sousa Luana , Altan Mehmet , Marques-Piubelli Mario L. , Dal Lago Eduardo Andreazza , Kaya Diana , Godoy Myrna , Kupferman Michael Elliot , Glisson Bonnie S. , El-Naggar Adel K. , Elamin Yasir Y
Published: October 2024

6019

Background:
ACC is a heterogeneous neoplasm and there is no standard treatment for patients (pts) with recurrent/metastatic (R/M) disease. Vascular endothelial growth factor receptor inhibitors (VEGFRi) are frequently used to treat R/M ACC rendering mostly disease stabilization. ACC is resistant to PD-1/PD-L1 inhibitors (PD-L1i), consistent with its low mutational burden and uninflamed immune microenvironment. We hypothesized that the immunomodulatory role of VEGFRi (axitinib) would enhance PD-L1i (Avelumab) activity and be a more effective therapy for R/M ACC.
Methods:
Eligible pts had R/M ACC with radiological or clinical progression within 6 months (mos) of enrollment. Treatment consisted of axitinib 5 mg PO bid and avelumab 10 mg/Kg IV every 2 weeks. Primary endpoint was objective response rate (ORR) per RECIST 1.1; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Simon 2-stage design was applied to test the null hypothesis of ORR ≤ 5% versus the alternative ORR ≥ 20%; ≥ 4 responses out of 29 pts was required to reject the null hypothesis.
Results:
41 pts enrolled from 07/24/19 to 06/29/21; 28 were evaluable for the primary endpoint (7 screen failures, 6 evaluable for safety only due to loss of insurance/logistics issues related to COVID-19 pandemic); 16 pts were treated in first-line. Mutation data was available for 23 of 28 evaluable pts; 7 had
NOTCH1
activating mutations. The ORR was 17.9% (5/28, 95%CI: 6.1-36.9%). One response was unconfirmed (pt progressed in non-target lesions 2 mos after achieving a PR), for a confirmed ORR of 14.3% (95%CI: 4-32.7%). The median follow-up time for the 15 alive pts was 11.6 mos (min-max: 7.7-29.2 mos). Median PFS was 7.2 mos (95%CI: 3.7-11.7 mos) with a 6-mos PFS rate of 57% (95%CI: 41-79%). Median OS was 17.4 mos (95%CI: 13-NA). 5 pts remain on therapy, 2/5 with a PR. The median DOR for the 5 responders was 5.2 mos (95% CI: 3.7–NA mos). The most common treatment-related adverse events (TRAEs) were fatigue (62%), hypertension (32%), diarrhea (29%), and stomatitis (29%). Serious TRAEs occurred in 8 (24%) pts, all grade 3 and manageable. 4 (15%) pts discontinued avelumab and 9 (32%) underwent axitinib dose reduction due to toxicity.
Conclusions:
The study reached its primary endpoint with ≥ 4 responses out of 28 evaluable pts (ORR of 17.8%; confirmed ORR of 14.3%). The ORR and 6-mos PFS rate of 57% with axitinib and avelumab compares favorably with single agent axitinib and warrants further study of the combination.
Clinical trial information: NCT03990571.
Preliminary safety and efficacy of toripalimab combined with cetuximab in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC): A phase Ib/II clinical trial.
Authors: Guo Ye , Li Zhendong , Chen Wantao , Fang Meiyu , Liu Zhigang ,   Shanghai Junshi Biosciences
Published: October 2024

6022

Background:
PD-1 inhibitors and EGFR inhibitors are effective and may provide potential synergy in R/M HNSCC. We launched an open-label, single-arm, multicenter phase Ib/II study of toripalimab (a humanized IgG4K monoclonal antibody specific for PD-1) with cetuximab in platinum-refractory R/M-HNSCC (NCT04856631). We report the results of the phase Ib portion of this study.
Methods:
Eligible patients with R/M HNSCC progressed upon 1
st
-line platinum-containing treatment or developed R/M disease within 6 months of platinum-containing neo-adjuvant/adjuvant or chemo-radiation therapy were enrolled in this study. Exclusion criteria included prior immunotherapy or EGFR inhibitors therapy. Toripalimab was administered at 240mg intravenously Q3W and cetuximab was given as a loading dose of 400mg/m
2
IV followed by 250mg/m
2
QW. Dose-limiting toxicities (DLTs) and de-escalating dose were evaluated by a Safety Monitoring Committee (SMC). If less than 2 DLTs were observed in the first 6 patients, 6 more patients were enrolled to confirm safety. If 2 or more DLTs were observed, the next 6 patients would be enrolled at a lower dose level. The primary endpoint was safety. Secondary endpoints included determination of recommended phase 2 dose (RP2D), ORR, DCR, DOR, and PFS by an independent review committee (IRC) per RECIST v1.1, OS, and PK.
Results:
A total of 13 patients were enrolled in the phase Ib portion, including 11 (84.6%) male and 2 (15.4%) female patients. The median age was 58 (range 36-74) years. 7 (53.8%) patients had distant metastases and 9 (69.2%) were PD-L1 CPS ≥1. By the data cutoff date of Dec 21, 2021, the median follow-up was 19.3 (1.6-36.3) weeks. No DLT was observed, and the initial dose was chosen as RP2D. 10 (76.9%) patients experienced TRAEs; the most common TRAEs were rash (46.2%) and paronychia (38.5%). 5 (38.5%) patients experienced irAEs, including immune-related skin adverse reactions, hypothyroidism, thyroid function abnormal and duodenitis. No Grade≥3 TRAEs or irAEs occurred. No TRAEs led to discontinuation of study drug. 2 patients reported fatal AEs, both of which were caused by tumor hemorrhage and were judged not related to the study treatment by the SMC. Among 12 patients with at least one post-treatment tumor assessment, 6 confirmed PR (ORR 50%) and 6 SD (DCR 100%) were observed as assessed by the IRC. By the cutoff date, 5 patients have ongoing responses, with 3 over 12 weeks.
Conclusions:
Toripalimab combined with cetuximab were well tolerated and showed preliminary clinical efficacy in patients with R/M HNSCC.
Clinical trial information: NCT04856631.
Infections and their impact on patients on pembrolizumab-based therapies for head and neck cancer.
Authors: Zhang Yuqi , Xu Jiaqiong , Muhsen Ibrahim , Burns Ethan , Shah Shivan M , Umoru Godsfavour , Mylavarapu Charisma , Sun Kai , Crenshaw Aubrey , Esmail Abdullah , Kieser Ryan Blair , Guerrero Carlo , Gong Zimu , Gee Kelly , Heyne Kirk , Singh Monisha , Zhang Jun , Abdelrahim Maen
Published: October 2024

6035

Background:
Immune checkpoint inhibitors (ICIs) stimulate the antitumor activity of the adaptive immune response and are used in combination with chemotherapy or as a monotherapy in metastatic head and neck squamous cell carcinoma (mHNSCC). Infections are known to impact outcomes in patients receiving chemotherapy, but the incidence and impact in patients receiving ICI is poorly defined. This analysis aims to identify the infectious burden and associated impact on clinical outcome in patients receiving pembrolizumab for mHNSCC.
Methods:
This is a retrospective study across 7 hospitals analyzing patients who received pembrolizumab from 1/1/2017-8/1/2021 and followed until 12/1/2021. Patients with mHNSCC that received pembrolizumab were dichotomized into infected and uninfected cohorts. Comparative covariates included gender, race, ECOG, comorbidities, anti-infectives use at ICI initiation, chronic infections, line of therapy (first or 1L, second or 2L, or > 2L). Risk factors for infections were assessed by univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI). Morbidity and mortality was assessed by all-cause emergency department (ED), inpatient, and intensive care unit (ICU) admissions, median cycles of ICI-based therapy, and overall survival (OS). OS was assessed via Kaplan-Meier analysis. P-value < 0.05 was considered statistically significant.
Results:
Of the 45 evaluable patients with mHNSCC, 22 (48.9%) had at least one infection. Baseline characteristics and comorbidities were similar across cohorts. Risk factors for developing infection included anti-infective use at ICI initiation (OR 13.27, 95% CI: 1.13-156.53, p = 0.04). Fewer infections were observed with ICI as > 2L compared to 1L (OR 0.1, 95% CI: 0.01-0.91, p = 0.041). Infection was the primary cause of death in 2 (9.5%) patients. Compared to the uninfected, infected patients received fewer cycles of therapy (4 vs 7, p = 0.026), and were more frequently admitted to the hospital [20 (90.9%) vs. 8 (34.8%), p < 0.001)] and ICU [5 (11%) vs. 0, p = 0.022]. Number of ED visits were similar at 8 (36.4%) in the infected vs. 5 (21.7%) in the uninfected (p = 0.28). At median follow-up of 8 months, 13 (59.1%) in the infected cohort and 8 (34.8%) in the uninfected had died (p = 0.1). Median OS was significantly lower in the infected (9.2; 95% CI 4.9-12.8 months) compared to the uninfected (28.1; 95% CI 14.3-unreached months) (p = 0.009).
Conclusions:
For mHNSCC patients on pembrolizumab, infections are more common in the 1L setting and is associated with fewer treatment cycles, more hospitalizations, and significantly shorter OS. Risk factors for infection include anti-infective use at ICI initiation.
Phase I results of gunagratinib (ICP-192), a highly selective irreversible FGFR 1-4 inhibitor in patients with head and neck cancer harboring FGF/FGFR gene aberrations.
Authors: Guo Ye , Li Qun , Tang Wenbo , Lin Fengjuan , Xue Junli , Xue Liqiong , Ge Xiaoxiao , Zhao Wei , Zhou Wei , Zhao Renbin , Zhang Bin , Li Jin
Published: October 2024

6039

Background:
The fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling pathway has been evaluated as critical driver of carcinogenesis in multiple cancer types. However, primary results of several FGFR inhibitors showed no or limited response in head and neck cancer (HNC) with FGF/FGFR gene aberrations. Here, we evaluated the efficacy and safety of a novel irreversible pan-FGFR inhibitor gunagratinib in HNC in a first-in-human, phase I/IIa, dose escalation and dose expansion study (ICP-CL-00301 NCT03758664).
Methods:
In the dose-escalation stage of ICP-CL-00301 study, patients with advanced solid tumors (including HNC) with or without FGF/FGFR gene alterations were treated with escalating doses (range: 2mg-26mg) of gunagratinib once daily in 21-day cycles until disease progression or unacceptable toxicity.
Results:
12 HNC patients with or without FGF/FGFR aberrations, including FGF amplification and FGFR mutation, were treated with escalating doses (range: 14mg-22mg) of gunagratinib. Among them, 9 patients harbored FGF/FGFR gene alterations with at least one tumor assessment. The median age of the 12 treated HNC patients was 56 (range: 44 to 75 years) with 75% male and ECOG performance status 1. Among the 9 HNC patients with FGF/FGFR gene aberrations who have completed at least one tumor assessment, 3 patients had partial response (PR), the overall response rate (ORR) was 33.3% (3 of 9 patients). The disease control rate (DCR) was 66.7% (6 of 9 patients). Total of 62 patients with solid tumor were enrolled in ICP-CL-00301 study. The most common treatment-related adverse events (TRAEs) (≥15%) included hyperphosphatemia, diarrhea, increased ALT or AST, increased alkaline phosphatase, hypercalcemia, increased serum creatinine, dry mouth, hypertriglyceridemia, anemia and hyperuricemia. In ICP-CL-00301 study, 3 serious TRAEs were reported, and no serious TRAE were reported in HNC patients.
Conclusions:
This study demonstrated the anti-tumor activity of gunagratinib in HNC patients carrying FGF/FGFR gene aberrations with an ORR of 33.3%. Gunagratinib is safe and well-tolerated in patients with advanced solid tumors including HNC.
Clinical trial information: NCT03758664.

Tumor histological type and gene alteration type.

Histological Type

N=12
[1]

 squamous cell cancer
8

 Ameloblastic carcinoma
2

 Nasopharyngeal carcinoma
3

Gene alterations Type

N=10
[2]

 FGF
7

 FGFR
3

[1]
One patient was a nasopharyngeal carcinoma patient with tongue squamous cell cancer.
[2]
One patient had no imaging tumor evaluation.
PDS0101, a novel type I interferon and CD8 T-cell activating immunotherapy, in combination with pembrolizumab in subjects with recurrent/metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC).
Authors: Weiss Jared , Chintakuntlawar Ashish V. , Price Katharine Andress Rowe , Kaczmar John M. , Riebel Nathalie , Bedu-Addo Frank K , Chaney Marya F. , Wood Lauren V
Published: October 2024

6041

Background:
Human papillomavirus (HPV) E6/E7 oncoproteins mediate immune evasion by down-regulating Type 1 interferons, TLR9, MHC Class I/II as well as other mechanisms, resulting in persistent infection and initiation of ̃5% of all cancers globally. Similarly, established cancers evade immune surveillance utilizing parallel mechanisms including the expression of checkpoint proteins. PDS0101 is a molecularly targeted immunotherapeutic based on an enantiospecific cationic lipid nanoparticle platform containing HPV16 neoantigens that exhibits anti-tumor activity with checkpoint inhibitors (CPIs) by upregulating Type I interferons and promoting antigen processing and cross presentation. This allows generation of high levels of polyfunctional HPV16-specific CD8 and CD4 T cells
in vivo
as well as immune memory. VERSATILE-002 (NCT04260126) is a phase 2 study of the combination of PDS0101 and pembrolizumab in treatment of CPI naïve and refractory patients with recurrent or metastatic HPV16-related HNSCC. Herein, we report preliminary safety and efficacy data for CPI naïve patients at a prespecified interim analysis.
Methods:
Subjects are treated with pembrolizumab 200mg IV every three weeks plus SC PDS0101 following pembrolizumab on days one of Cycles1-4 and Cycle12; pembrolizumab continues up until 35 cycles, disease progression or intolerance to therapy.
Results:
Eighteen CPI naïve subjects with confirmed HPV16 tumors and a CPS score > = 1, median age 62 yrs (range 46-71), all male, 17 (94%) of whom were White and 16 (88.9%) not Hispanic or Latino, received at least one cycle of combination therapy. At the time of analysis, 17 (94%) subjects had received > = 4 doses of PDS0101 (median 4, range 1-5) and pembrolizumab (median 7, range 1-14). There were no Grade 3 or greater treatment-related toxicities and no drug discontinuation related to toxicity or immune-related AEs. Clinical activity (CR+PR+SD) was seen in 13 (72.2%) of 18 subjects, with best overall reponse per RECIST1.1 documenting: OR in 7 (38.9%; 2 CR, 5PR); stable disease (SD) in 6 (33.3%) and progressive disease in 3 (16.7%); 2 subjects had missing data. Tumor reduction was seen in 4 of 6 (67%) subjects with SD. Nine-month PFS and OS rates (95% CI) were 52% (22.5, 74.7) and 81% (37.8, 95.5) respectively; median PFS and OS have not been reached.
Conclusions:
The combination of PDS0101 and pembrolizumab demonstrates an excellent safety profile with preliminary evidence of clinical activity in the majority of CPI naïve patients with HPV-related HNSCC.
Clinical trial information: NCT04260126.
Refueling a Quiet Fire: Old Truthers and New Discontent in the Wake of COVID-19
Authors: Beccari Gabriele , Giaccherini Matilde , Kopinska Joanna , Rovigatti Gabriele
Published: October 2024

This article investigates the factors that contributed to the proliferation of online COVID skepticism on Twitter across Italian municipalities in 2020. We demonstrate that sociodemographic factors were likely to mitigate the emergence of skepticism, whereas populist political leanings were more likely to foster it. Furthermore, pre-COVID anti-vaccine sentiment, represented by “old truthers” on Twitter, amplified online COVID skepticism in local communities. Additionally, exploiting the spatial variation in restrictive economic policies with severe implications for suspended workers in nonessential economic sectors, we find that COVID skepticism spreads more in municipalities significantly affected by the economic lockdown. Finally, the diffusion of COVID skepticism is positively associated with COVID vaccine hesitancy.
Impossible Things
Authors: Oberman Miller
Published: October 2024

Impossible Things is a book of poems considering fatherhood through the lens of transgender and Jewish identity with a focus on the impact of generational trauma. These poems (accompanied by two short essays) explore the way that the loss of a single child can reverberate for generations. Largely through the lens of the lyric, Impossible Things consider the author’s experiences as a transgender child and father, reflecting on his fraught relationship with his own father, who died in 2006. Weaving in passages from the poet’s father’s unpublished memoir in the form of erasure poems, Impossible Things presents a fractured and incomplete memoir, as it engages with the mysterious drowning of the poet’s brother, Joshua, at age two, a tragedy that cast a shadow over his childhood. By using forms such as the cento, which builds a poem from a patchwork of voices, these poems embrace intertextuality beyond their relationship with the author’s father’s memoir, connecting, through text, chosen family to family of origin. In making an intertextual, transtemporal space where the poet’s voice and his father’s can meet on the page, Impossible Things moves through time to create a conversation with the past, speaking to the possibilities for healing generational trauma, even when the original survivors have become our ancestors.
Απομάκρυνση παιδιών από την οικογένεια λόγω κακοποίησης
Authors: Αλεβίζος Στέφανος
Published: October 2024

Το ζήτημα της κακοποίησης ή / και παραμέλησης παιδιών απασχολεί την επιστημονική κοινότηταπάρα πολλές δεκαετίες. Ειδικά τα τελευταία χρόνια υπάρχει εκτεταμένη επιστημονική έρευναγύρω από την φύση και τις μορφές της κακοποίησης ή / και παραμέλησης με στόχο την ανάδειξησημαντικών ενδείξεων τόσο για την ανίχνευση όσο και για την πρόληψη της κακοποίησης. Επιπλέον η έρευνα επεκτάθηκε και στο πλαίσιο εναλλακτικής φροντίδας, αν και εφόσον κριθείαναγκαίο το παιδί να απομακρυνθεί από το σπίτι του. Συνεπακόλουθα και με βάση τιςεπιστημονικές έρευνες εμπλουτίσθηκε το νομικό πλαίσιο με νόμους, εγκυκλίους και άλλεςπράξεις. Η ίδια όμως η διαδικασία της απομάκρυνσης δεν έχει ερευνηθεί διεξοδικά και δενυπάρχει καμία αναφορά σε νομικό κείμενο για το πώς πρέπει να γίνονται οι απομακρύνσεις. Μετην παρούσα έρευνα επιχειρείται να διερευνηθεί η διαδικασία της απομάκρυνσης και οιεπιπτώσεις της ως τραυματική εμπειρία για τα παιδιά. Εκτός από την βιβλιογραφική έρευνα,διεξήχθη ποιοτική έρευνα μέσω συνεντεύξεων σε ενήλικες επιζώντες και επιζώσες κακοποίησηςμε εμπειρία απομάκρυνσης στην παιδική τους ηλικία. Τα αποτελέσματα έδειξαν ότι ακόμη καιστις περιπτώσεις που τα ενήλικα άτομα ως παιδιά κατανοούσαν την ανάγκη της απομάκρυνσης,η πράξη της απομάκρυνσης υπήρξε τραυματική και βίαιη με αποτέλεσμα να καθιερωθεί ηορολογία «Το Τραύμα Βίαιης Απομάκρυνσης». Τέλος αναδείχθηκε η ανάγκη για νομοθετικήπλαισίωση της πράξης της απομάκρυνσης, βασισμένη σε επιστημονικά ευρήματα.
Τρισδιάστατη διανυσματική μοντελοποίηση και μέθοδοι υπολογισμού του βαρυτικού και του μαγνητικού πεδίου πεπερασμένων κατανομών
Authors: Αναστασιάδης Κωνσταντίνος
Published: October 2024

Η διδακτορική διατριβή μου έχει τίτλο “Τρισδιάστατη διανυσματική μοντελοποίηση και μέδοδοι υπολογισμού του βαρυτικού και του μαγνητικού πεδίου πεπερασμένων κατανομών” και η τριμελής συμβουλευτική επιτροπή, αποτελούμενη από τους Καθηγητές του ΤΑΤΜ κκ Γ. Βέργο, Χ. Κωτσάκη και Δ. Τσούλη, ορίστηκε από την αρ. 13/26-8-2020 Συνέλευση Τμήματος. Ως επιβλέπων Καθηγητής ορίστηκε ο κ. Τσούλης Δημήτριος. Στη διατριβή του ο κ. Αναστασιάδης εξετάζει τη διανυσματική μοντελοποίηση του βαρυτικού και του μαγνητικού πεδίου πεπερασμένων κατανομών. Πρόκειται για μία αναλυτική μεθοδολογία που οδηγεί σε κλειστές σχέσεις για τον υπολογισμό του βαρυτικού και του μαγνητικού σήματος μίας πεπερασμένης τρισδιάστατης κατανομής, επιτρέποντας μία ενιαία θεώρηση της περιγραφής των δύο αυτών πεδίων. Στα πρώτα δύο κεφάλαια γίνεται μία πρώτη εισαγωγή στο θεωρητικό υπόβαθρο του αντικειμένου της διατριβής, που είναι οι βασικές εξισώσεις του πεδίου ελκτικών δυνάμεων του Νεύτωνα και της θεωρίας δυναμικού. Στο τρίτο κεφάλαιο πραγματοποιείται η λεπτομερής παρουσίαση της διανυσματικής μεθόδου. Δίνονται οι ορισμοί βασικών παραμέτρων, όπως του διανύσματος b. Ο υπολογισμός των αναλυτικών εκφράσεων βασίζεται στην εφαρμογή του θεωρήματος Gauss σε συνδυασμό με το θεώρημα Stokes. Σε αντίθεση με άλλες αναλυτικές μεθοδολογίες που απαιτούν συνεχείς προβολές του σημείου υπολογισμού σε διαφορετικά επίπεδα και ορισμούς νέων συστημάτων συντεταγμένων και των σχετικών μετασχηματισμών, η διανυσματική μέθοδος βασίζεται στη σχέση μεταξύ σημείου υπολογισμού και την πραγματική διάσταση των επί μέρους ακμών που ορίζουν την πολυεδρική κατανομή διανυσματικά. Το τέταρτο κεφάλαιο πραγματεύεται τις αριθμητικές αστάθειες όταν μεγαλώνει η απόσταση μεταξύ του σημείου υπολογισμού και της διαταρακτικής πηγής. Όταν ο λόγος της απόστασης από το σημείο υπλογισμού μέχρι το τοπικό σημείο ορισμού, προς το μήκος της ακμής του πολυέδρου αυξάνεται, τότε η ακρίβεια που απαιτείται αυξάνεται εκθετικά πάνω από την τάξη μεγέθους των ολοκληρώσεων που απαιτούνται. Εισάγοντας μία βοηθητική παράμετρο offset μέσα στον αλγόριθμο, το πρόβλημα απομακρύνεται και οι υπολογισμοί ομαλοποιούνται. Το πέμπτο κεφάλαιο περιλαμβάνει μία σειρά αριθμητικών εφαρμογών στα παραδείγματα μοντέλων αστεροειδών Eros433 και Didymos καθώς και σε τετράεδρο.
Το δημοσιευμένο και αδημοσίευτο μουσικό έργο του Δημήτρη Γκόγκου-Μπαγιαντέρα
Authors: Μπαρμπάτσης Ανέστης
Published: October 2024

Το δημοσιευμένο και αδημοσίευτο μουσικό έργο του Δημήτρη Γκόγκου-Μπαγιαντέρα. Μουσική μεταγραφή και ανάλυση. Ο Δημήτρης Γκόγκος ή Μπαγιαντέρας γεννήθηκε στον Πειραιά στις αρχές του 20ού αιώνα, μια χρονική συγκυρία μεγάλων ιστορικών και κοινωνικών εξελίξεων. Οι πόλεμοι, οι διχασμοί, τονώνουν το εθνικό φρόνημα και δημιουργούν την ανάγκη για ενιαία ταυτότητα και την πολυσυζητημένη στροφή προς τη δύση. Στη μουσική πραγματικότητα της εποχής, η συνθήκη αυτή, είχε ως αποτέλεσμα την έλευση μιας πιο «δυτικότροπης» μουσικής κουλτούρας και την παρακμή των «ανατολιτικότροπων», μουσικών χαρακτηριστικών, μιας μουσικής παράδοσης η οποία ήταν κυρίαρχη κατά το παρελθόν. Ο Μπαγιαντέρας υπήρξε ένας από τους σημαντικούς εκπροσώπους του πειραιώτικου ρεμπέτικου με βάση το μπουζούκι, καθώς, ως γεννημένος στον Πειραιά, βίωσε την πορεία και την εξέλιξή του, πριν την πρώτη του καταγραφή σε δίσκο. Σύμφωνα με τη θέση ότι το ρεμπέτικο είναι συγκερασμός «ανατολίτικότροπων» και «δυτικότροπων» μουσικών χαρακτηριστικών, θα μπορούσαμε να πούμε ότι ο Μπαγιαντέρας έζησε το πλαίσιο συνύπαρξης, εξέλιξης και ενσωμάτωσης αυτών, στο «νέο αστικό λαϊκό τραγούδι». Άλλωστε, οι δυτικότροπες επιρροές κατείχαν σημαντικό ρόλο στα πρώτα του ακούσματα, γεγονός που σηματοδότησε και το παρωνύμιο Μπαγιαντέρας με το οποίο έγινε γνωστός στο ευρύ κοινό. Προερχόταν από φιλόμουσο οικογενειακό περιβάλλον, το οποίο τον ώθησε στο να ασχοληθεί με τα ευρέως διαδεδομένα μουσικά όργανα των αρχών του 20ου αιώνα στον Ελλαδικό χώρο, το πιάνο, την κιθάρα, το βιολί και το μαντολίνο. Με γνώμονα τις πρώτες ηχογραφήσεις-εκτελέσεις, τα μουσικά παραδείγματα μεταγράφουν όλα τα μουσικά όργανα που συμμετέχουν σε αυτές, προκειμένου να έχουμε μια πιο σαφή εικόνα για το οργανολόγιο, την εξέλιξη της λαϊκής ορχήστρας, την τροπικότητα τον διαστηματικό κόσμο, την αρμονική και ρυθμολογική συγκρότηση, τη μουσική φόρμα, την ενορχήστρωση, τις τεχνικές παιξίματος, αλλά και το επιτελεστικό πλαίσιο. Μια προσέγγιση και μελέτη του μουσικού υλικού με τη χρήση μουσικολογικών εργαλείων και κριτηρίων, με στόχο την ερμηνεία και παρουσίαση του μουσικού συντακτικού του συνθέτη. Οι ερευνητικοί στόχοι της διατριβής, μπορούν να συνοψιστούν στα εξής: • Μουσική μεταγραφή και ανάλυση του δημοσιευμένου και αδημοσίευτου έργου. • Ανάλυση και σχολιασμός της εξέλιξης της δομής της ορχήστρας. • Παρουσίαση της γραμματείας των χειρογράφων στίχων και μουσικής και της συνθετικής τεχνοτροπίας του. • Έρευνα, μεταγραφή, εναρμόνιση και ενορχήστρωση των ανέκδοτων δημιουργιών. Ένας επιπλέον στόχος, αποτελεί η δημόσια, μουσική παρουσίαση μέρους των ανέκδοτων δημιουργιών του.
Predicting the incidence of recurrent positive exercise stress tests among civilian pilots: a retrospective cohort study
Authors: Herry Voltha , Widyahening Indah Suci , Afian Ferdi , Wijaya Ika Prasetya , Chew Boon-How , Soemarko Dewi Sumaryani
Published: October 2024

Abstract* Background A positive exercise stress test (EST) is common among pilots, and it may indicate a greater risk of coronary artery disease (CAD). This study aimed to determine the incidence of recurrently positive EST and their predictors among civilian pilots in Indonesia. Methods This was a retrospective cohort study among civilian pilots who had the first positive EST test between January 2019 and June 2020 at the Aviation Medical Center, Jakarta. The data were retrieved from medical records. Subjects were included if there were data on subsequent ESTs at 6 and 12 months. Risk factors included total flight hours (TFH) in the last 6 months, license type, aircraft cabin pressurization system, flying limitation such as multicrew, cardiac intervention, age, smoking habit, family history of coronary artery disease, body mass index, blood pressure levels, lipid profile, and fasting blood glucose. Results Eighty-seven pilots were included; 54 of them (62.1%) had recurrent positive ESTs. All subjects were men, and the median age was 51 (range 40-64) years. Independent predictors of recurrent positive ESTs were age 60-65 years (adjusted odds ratio [ORadj]: 5.1, 95% CI: 1.12–23.16, p= 0.035), a TFH of > 275 hours (ORadj 5.1, 95% CI: 1.28–20.65, p= 0.021), and dyslipidemia (ORadj: 4.2 95% CI: 1.468–12.275, p=0.015). Having these three risk factors increased the probability of a recurrent positive EST up to 100%. Conclusion The incidence of recurrently positive ESTs among civilian pilots in Indonesia was high. Airlines may want to implement a more aggressive health policy for the prevention of cardiovascular diseases among their pilots.
Breaking point: Case series of tendon ruptures in Hemodialysis patients
Authors: Nazeer Muhammed Ehsan , Haphiz Dr Askhar , Nazeer Dr Muhammed , Moni Dr Pradeep , Muraleedharan Dr Praveen
Published: October 2024

Introduction Spontaneous tendon ruptures in end stage kidney disease patients have the potential to cause long- term morbidity, and timely intervention is required to prevent complications that can severely affect the functional status of the patient Case presentation A series of six tendons (two triceps tendons and two bilateral quadriceps tendons) in three patients with ESKD undergoing hemodialysis is discussed in this case series. Patients were aged 61, 44 and 26 years, and on hemodialysis for 5, 5 and 10 years, respectively. Conclusion End -stage kidney disease is associated with a multitude of physiological changes, and the musculoskeletal system is no exception to this. Spontaneous tendon rupture is a multifactorial complication of ESKD, with serious implications for mobility and quality of life. As a result, these patients require a multifaceted approach to ensure optimum results and an early return to activity. We report a series of 6 spontaneous tendon ruptures in 3 patients with ESKD at our institution. We would like to outline the methods of repair for each case and further attempt to assess biochemical parameters that may have contributed to the disease process.
Case Report: An Integrated Approach To Treating Infected Corneal Laceration With Traumatic Endophthalmitis In Paediatric Age Group
Authors: Shetty Prerana A , Singh Jashandeep , Kapoor Aditya , Bhalerao Sushank
Published: October 2024

This case report presents a case of infected corneal laceration with traumatic endophthalmitis in a pediatric patient. A boy in his middle childhood sustained an ocular injury with scissors, resulting in a full-thickness corneal laceration and infection. Despite the delay in seeking treatment, the patient underwent successful surgical interventions, including corneal scraping, pars plana lensectomy, vitrectomy, and secondary intraocular lens implantation (IOL). The infection was managed with targeted antibiotics, and Staphylococcus aureus was confirmed as the causative organism. Remarkably, these efforts led to a satisfactory improvement in the patient’s vision to 20/50. This case underscores the importance of early intervention and a multidisciplinary approach in the management of pediatric ocular trauma to optimize outcomes.
The role of Tai Chi in managing Parkinson's disease: A review of therapeutic mechanisms and clinical outcomes
Authors: Paziewska Adrianna Marta , Jurasz Karolina , Cymer Radosław , Rzeska Ewa , Rogulski Michał
Published: October 2024

Tai Chi is a traditional Chinese martial art characterized by maintaining postures and performing slow, fluid movements. This exercise involves actions like extending the knees and hips, shifting weight, flexing, rotating the trunk, and coordinating arm movements. All of this improves balance, motor coordination, and also mental stability. In this review, we explore the relationship between practicing Tai Chi and the improvement of physical abilities in individuals with Parkinson's Disease. We will also compare Tai Chi to other alternative methods for improving physical abilities.
Role of Spinal Cord Stimulation (SCS) in the Management of Failed Back Surgery Syndrome (FBSS) - a Comprehensive Literature Review
Authors: Połujański Paweł , Kowal Joanna , Cyran Piotr , Jaroszyńska Anna , Jaroszyński Filip , Paleczny Jan , Parobczak Robert , Winciorek Joanna , Wiśniewska Adrianna
Published: October 2024

Study Design
 
A literature review.
 
Objective
 
The assessment of the efficacy of Spinal Cord Stimulation (SCS) in treatment of Failed Back Surgery Syndrome (FBSS) in terms of chronic pain management, reducing the use of pain medication, improvement of the overall quality of life and cost-effectiveness of the method in comparison to conventional medical management (CMM) and spinal revision surgery.
 
Methods
 
A review of the clinical data from prospective studies, clinical trials and systematic reviews was conducted to provide on overview of the effectiveness of Spinal Cord Stimulation (SCS) in treatment of Failed Back Surgery Syndrome (FBSS).
 
Results and Conclusion
 
Numerous studies have proven the efficacy and safety of SCS in this patient population, in terms of managing neuropathic pain, reduction of pain medication use, quality of life improvement and cost-effectiveness as compared to CMM and re-operation. Careful preoperative patient selection and psychological screening is required in order to ensures optimal treatment results.
¿Baldío o privado? La determinación de la naturaleza jurídica de los predios en Colombia. Parámetros para la aplicación del artículo 48 de la Ley 160 de 1994
Authors: Romo Delgado Carlos Esteban
Published: October 2024

El presente artículo pretende establecer lineamientos para efectos de que los operadores de tierras puedan zanjar las ambigüedades interpretativas que se presentan a la hora de calificar la naturaleza jurídica de los predios. Desde criterios lógicos, históricos y teleológicos se establecen parámetros interpretativos de aplicación del artículo 48 de la Ley 160 de 1994 referente a las fórmulas de acreditación de propiedad privada, sustentando una visión transaccional que permitiría unificar criterios en los procedimientos y evitar que la calificación de un predio sea una actividad bizantina de paleografía que conllevaría a que tengamos que esperar otros 200 años para contar en Colombia con un inventario completo de la propiedad y así emprender con efectividad las reformas que nuestra sociedad requiere.
Industry-University Collaboration and Commercializing Chinese Corporate Innovation
Authors: Hsu David H. , Hsu Po-Hsuan , Zhou Kaiguo , Zhou Tong
Published: October 2024

We construct a comprehensive data set of medium- and large-sized industrial firms and research universities in China and examine how Chinese firms’ commercialization of their technologies is related to their experience in industry-university collaboration (IUC). We propose that firms’ IUC experience constitutes an inimitable complementary asset that facilitates their technology commercialization. Our empirical analyses show that firms generate more new product sales and produce more product-oriented patents when they have more patents that are coassigned to universities or when they have more academic publications coauthored with university staff in the past. Such a relation is strengthened when firms have higher absorptive capacity, when firms are in industries that depend more on basic science, and when firms are located closer to their collaborating universities. Additional tests point out four channels through which firms’ IUC experience benefits their technology commercialization: knowledge acquisition, talent recruiting, direct technology transfers, and technological complementarity.

This paper was accepted by Sridhar Tayur, entrepreneurship and innovation.

Funding: D. H. Hsu acknowledges research support from the Mack Institute for Innovation Management at the University of Pennsylvania. P.-H. Hsu acknowledges the Yushan Fellow Program by the Ministry of Education and National Science and Technology Council, Taiwan [MOE-108-YSFMS-0004-012-P1, NSTC 113-2410-H-007-008-MY3, MOST 109-2628-H-007-001-MY4] and the E.SUN Academic Award. K. Zhou acknowledges research support from the Major Project of the National Social Science Fund of China [Grant 20&ZD103], the National Natural Science Foundation of China [Grant 71991474] and the 111 Project of China [Grant D23001]. T. Zhou acknowledges research support from the National Natural Science Foundation of China [Grant 72003206].

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.00788 .