bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant therapy of camrelizumab combined with chemotherapy in patients (pts) with resectable esophageal squamous cell cancer (ESCC): A single-center, single-arm, exploratory clinical trial.
Authors: Yang Ji chen , Jiao Wenjie , Hua Feng , Zhao Xiaoming , Yang Wenfeng 
Published: August 2024

e16095 Background: The study aimed to evaluate the efficacy and safety of neoadjuvant therapy of camrelizumab, combined with chemotherapy in resectable ESCC pts and explore factors related to efficacy. Methods: Patient with resectable ESCC, staged as cT1b-cT2N+ or cT3-cT4aNany were enrolled. Eligible pts received camrelizumab (200 mg, d1) combined with nab-paclitaxel (200 mg/m2, d1) and nedaplatin (75 mg/m2, administered on an average of two days) and S-1 (50mg/m2, bid, d1-14) for 2 or 3 cycles (21 days per cycle) before surgery. The primary endpoints were pathological complete response (pCR) rate. Results: From Aug 25, 2022, to Nov 17, 2023, a total of 53 pts were enrolled in this study and completed 2 or 3-cycle neoadjuvant therapy. Median age was 58(54-63), 47 males and 6 females, The primary site was upper segment in 3 pts, middle segment in 27 pts, and lower segment in 23 pts, The clinical T staging was T2 in 2 pts, T3 in 49 pts, and T4 in 2 pts. The clinical N staging was N0 in 8 pts, N1 in 28 pts, N2 in 16 pts, and N3 in 1 pt. The physical condition score was 0 for 16 pts, and 1 for 27 pts. 37 pts underwent surgery and R0 recetion was achieved in 37 (100%) pts. pCR(ypT0N0) was identified in 9(24.3%) and 3(8.1%) pts had conplete response of primary tumor but residual didease in lymph nodes alone (ypT0N+), the MPR was was identified in 5(13.5%) pts. Of pts who underwent surgery, 25(67.6%) received 3-cycle and 12(32.4%) received 2-cycle neoadjuvant therapy, the pCR rate was 32% and 8.3%,respectively. According to tumor regression grade, 12 (11(44%) in 3-cycle and 1(8.3%) in 2-cycle) pts had TRG0, 5(4(16%) in 3-cycle and 1(8.3%) in 2-cycle) TRG1, 15 (9(36%) in 3-cycle and 6(50%) in 2-cycle) TRG2, and 4 (all 4(33.3%) in 2-cycle) TRG3. Also we found there was no relationship between the NK cells, B cells, total T lymphocytes, Th cells, Tc/Ts cells, CD4+/CD8+ratio and the pCR and MPR rate. The most common AEs were anemia (71.7%)、 lymphocyte count decreased (67.9%)、white blood cell count decreased (52.8%) and neutrophil count decreased (52.8%). Most AEs were grade 1-2. No grade 4/5 AEs occurred. Conclusions: The short-term efficacy and safety of camrelizumab combined with three drugs chemotherapy were similar to previous research combined with two drugs.The efficacy of three-cycle regimen seems to be significantly better than the two-cycle regimen, which may indicate that the two-cycle neoadjuvant therapy is still insufficient, and confirmatory results need to be verified through large-scale clinical studies. Clinical trial information: ChiCTR2300068185.
INTASYL PH-762: PD-1 intratumoral immunotherapy for cutaneous carcinoma.
Authors: Spellman Mary C , Furst Katharine , Mahoney Linda 
Published: August 2024

TPS9620 Background: Immune checkpoint-targeted antibodies directed at PD-1 or PD-L1 block co-inhibitory receptors expressed by anti-tumor T cells, breaking immune tolerance against tumor cells and generating cancer immunity. Intratumoral (IT) immunotherapy aims to use the tumor as a ‘self-vaccine’. Local immune stimulation may induce robust priming of an anti-tumor immune response and generate abscopal tumor responses, mediated by circulating activated anti-tumor immune cells. Local delivery of immunotherapy minimizes systemic exposure and off-target toxicities and may decrease tumor size and improve surgical morbidity. PH-762 is an INTASYL compound designed to precisely silence PD-1 mRNA. INTASYL is a patented, self-delivering RNAi technology platform designed to impart specific properties to small interfering RNAs. PH-762’s unique structural and chemical modifications ensure an optimized cell and tissue uptake profile with IT administration. In vitro investigations have demonstrated efficient uptake of PH-762 by human T cells, silencing of PD-1 mRNA and subsequent protein reduction. Preclinical studies have shown that IT injections of murine-targeted PH-762 (mPH-762) can silence PD-1 mRNA in T cells within the tumor and increase the secretion of IFN-γ. mPH-762 was well tolerated at the maximum administered dose and treatment with mPH-762 provided robust and statistically significant inhibition of tumor growth. Toxicokinetic studies conducted in marmoset monkeys demonstrated that PH-762, when administered intravenously at doses of up to 147 mg/kg, is well-tolerated. No cytokine-release associated cytokines were detected in the plasma of treated monkeys at this dose. Methods: This open-label Phase 1 clinical study (NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant use of IT PH-762 in cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma, to determine the pharmacokinetic profile of PH-762 after IT injection, to observe pathologic and immunologic tumor responses, and to determine the recommended dose for development. Escalating dose concentrations of PH-762 (from 1.14 mg/mL through 22.00 mg/mL) are tested serially in cohorts of 3 patients each. Patients receive IT PH-762 once weekly, 4 times over a 3-week period prior to surgical excision, which occurs 5 weeks after the initial injection. Following excision of the tumor, patients are followed for approximately 11 weeks. Tumor changes are evaluated per iRECIST criteria and pathological response. Immunological response in tumor tissue and blood samples are assessed as secondary endpoints. This clinical study, enrolling patients since November 2023, will establish the basis for continued clinical development of PH-762. Clinical trial information: 06014086.
Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238
Authors: Weber Jeffrey , Del Vecchio Michele , Mandalá Mario , Gogas Helen , Arance Ana M. , Dalle Stephane , Cowey C. Lance , Schenker Michael , Grob Jean-Jacques , Chiarion-Sileni Vanna , Márquez-Rodas Iván , Butler Marcus O. , Di Giacomo Anna Maria , de la Cruz-Merino Luis , Arenberger Petr , Atkinson Victoria , Hill Andrew , Fecher Leslie A. , Millward Michael , Khushalani Nikhil I. , Queirolo Paola , Long Georgina V. , Lobo Maurice , Askelson Margarita , Ascierto Paolo A. , Larkin James 
Published: August 2024

PURPOSE
In phase III CheckMate 238, adjuvant nivolumab significantly improved recurrence-free survival compared with ipilimumab in patients with resected stage IIIB-C/IV melanoma without a significant difference in overall survival (OS). Here, we investigate progression-free survival (PFS) and OS after postrecurrence systemic therapy.

PATIENTS AND METHODS

Patients 15 years or older with resected stage IIIB-C/IV melanoma were stratified by stage and tumor PD-L1 status and randomly assigned to receive nivolumab 3 mg/kg every 2 weeks, or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks for 1 year or until disease recurrence, unacceptable toxicity, or withdrawal of consent. Patients with recurrence in each group were assessed for PFS and OS from subsequent systemic therapy (SST) initiation per recurrence timing (≤12 months [early]
v
>12 months [late] from initial therapy).

RESULTS

Recurrences occurred in 198 (44%) of 453 nivolumab-treated patients (122 early, 76 late) and 232 (51%) of 453 ipilimumab-treated patients (160 early, 72 late). Median PFS on next-line systemic therapy for nivolumab-treated patients recurring early versus late was 4.7 versus 12.4 months (24-month rates, 16%
v
31%); median OS was 19.8 versus 42.8 months (24-month rates: 37%
v
73%). In response to subsequent therapy, patients on nivolumab with late versus early recurrence were more likely to benefit from anti–PD-1 monotherapy. Nivolumab-treated patients with either an early or late recurrence benefitted from an ipilimumab-based therapy or targeted therapy, each with similar OS.

CONCLUSION
Postrecurrence survival was longer for patients who recurred >12 months. Patients on nivolumab who recurred early benefitted from SST but had better survival with ipilimumab-based regimens or targeted therapy compared with anti–PD-1 monotherapy.
Landscape of Concomitant Driver Alterations in Classical EGFR-Mutated Non–Small Cell Lung Cancer
Authors: Wang Huaying , Lin Lie , Liang Chuqiao , Pang Jiaohui , Yin Jiani C. , Zhang Junli , Shao Yang , Sun Chengming , Guo Renhua 
Published: August 2024

PURPOSE Next-generation sequencing (NGS) has enabled the detection of concomitant driver alterations in non–small cell lung cancer (NSCLC). However, the magnitude and clinical relevance of concomitant drivers remain to be explored. METHODS We profiled concomitant driver alterations of EGFR+ NSCLC by using targeted NGS. The associated genomic and clinical features were analyzed and validated in an independent The Cancer Genome Atlas cohort of patients with EGFR+ NSCLC. RESULTS Out of the total patient population, 334 patients had EGFR mutations along with concomitant driver mutations, comprising 3.09% of the entire cohort. The most frequent co-occurring mutations with sensitizing EGFR mutations include KRAS at 53.9%, followed by ERBB2 at 24.3%, MET at 16.5%, and BRAF at 3.3%. KRAS mutations in concomitant drivers were frequently hyperexchange mutations (25.6% v 8.2%, P < .001), compared with KRAS single drivers. EGFR/ ERBB2 drivers exhibited a higher incidence of ERBB2 amplification (40.7% v 16.5%, P < .001) and p.S310F/Y mutations (44.4% v 4.3%, P < .001) compared with ERBB2 alone. EGFR/ MET drivers had a higher frequency of MET amplification (71.4% v 43.3%) than MET single drivers. At the genomic level, the median number of additional concurrent mutations was four, with TSC2 (4%), CD274 (1%), and TP53 (63%) being the most frequently coaltered genes in concomitant driver tumors. Interestingly, clonality analysis indicated that EGFR mutations were more likely to occur as clonal events, whereas the codrivers were more often subclonal. Patients with concomitant drivers or with concomitant MET amplification exhibited worse prognosis. CONCLUSION These findings might aid in the selection of effective therapeutic regimens and facilitate the development of combination therapies.
Molecular Differences With Therapeutic Implications in Early-Onset Compared With Average-Onset Biliary Tract Cancers
Authors: Jayakrishnan Thejus , Baca Yasmine , Xiu Joanne , Patel Mehrie , Weinberg Benjamin A. , Lou Emil , Datta Jashodeep , Khushman Moh'd , Gulhati Pat , Goel Sanjay , Biachi de Castria Tiago , Florou Vaia , Nair Kanika G. , Kamath Suneel D. , Khorana Alok A. 
Published: August 2024

PURPOSE Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set. METHODS The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (<50 years for eoBTC, ≥50 years for aoBTC). P values were adjusted for multiple testing and considered significant at Q < 0.05 (molecular comparisons) or Q < 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis. RESULTS The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). FGFR2 fusion (15.7% in eoBTC v 5.9% in aoBTC) and NIPBL fusion (1.1% v 0%) were significantly more prevalent in eoBTC (both Q < 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; Q = 0.01) and T-cell inflammation score (FC, 17.3; Q = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; Q = 0.16), whereas IFG (NES = –1.58; Q = 0.06) and inflammatory response (NES = –1.46; Q = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, P = .004. The median OS by FGFR2 fusion (with fusion v without) was 21.7 versus 15.0 months ( P = .47) for eoBTC and 18.6 versus 12.2 months ( P < .001) for aoBTC. CONCLUSION We identified crucial differences including higher prevalence of FGFR2 fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the FGFR2 fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets.
Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma
Authors: Cremin Carol , Bedard Angela C. , Hong Quan , Mung Sze Wing , Nuk Jennifer , Wong Andrew , Akbar Husain , Cheung Eugene , Renouf Daniel , Schaeffer David , Sun Sophie , Schrader Kasmintan A. 
Published: August 2024

PURPOSE Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic–initiated testing (HCT) pathway and a new oncology clinic–initiated testing (OCT) pathway. METHODS Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022. Charts were retrospectively reviewed for patient characteristics and testing outcomes. RESULTS The study population was 397 patients (HCT, n = 279 and OCT, n = 118). OCT patients were more likely to have non-European ethnicity compared with HCT patients (41.9% v 25.6%, P = .004), to have earlier-stage disease ( P = .012), and to have better Eastern Cooperative Oncology Group performance status than the HCT group ( P = .001). A total of 306 patients completed testing (77%). OCT patients had higher test completion rates than HCT patients (odds ratio, 3.74 [95% CI, 1.66 to 9.62]). Median time for results was shorter in OCT than in HCT (53 days [IQR, 44-76] v 107 days [IQR, 63.8-158.3]). Pancreatic cancer susceptibility pathogenic gene variants were identified in 8.5% (26/306). CONCLUSION The real-world observations in our study show that oncology clinic–initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. This has important implications for publicly funded environments with limited resources for genetic counseling.
The Political Economy of Lauchlin Currie's Land Tax Policy in Wartime China
Authors: Chao Hsiang-Ke , Lin Hsiao-ting 
Published: August 2024

Abstract
This article examines Lauchlin Currie's land tax policy suggestion during wartime China and its political economy. Our study, based on unpublished archival materials, aims to clarify the reasons for and outcomes of Currie's first visit to China in 1942. It is argued that Currie, acting as a sincere adviser, based his policy recommendation on extensive surveys of the political and economic conditions of wartime China. In his efforts to persuade the Chinese leader Chiang Kai-shek to implement financial reform, Currie drew on the authority of Sun Yat-sen's economic thought and the leadership analogies of Franklin Roosevelt and New Deal policies.
Race, Time, and the Petrified Subject in Algeria
Authors: McManus Anne-Marie 
Published: August 2024

Abstract
Two major thinkers of anti-colonialism in Algeria—Kateb Yacine, author of the novel Nedjma (1956), and Frantz Fanon—described the impacts of colonial violence through figures of petrification that blur the border between human and nonhuman. Their works ground this article's relational reading across anti-Black and anti-Algerian racializations, drawing on Sylvia Wynter's concept of rhythmic reading and scholarship on comparative racialization. Petrification seeks to capture subjective absence: a modality of living as a negated subject who is excluded from the category of the human. This relational frame suggests absence as a plural, disappearing mode of knowledge production under colonialism. Yacine's novel fleshes out alternative modalities of being human that appear, in Fanon's Algerian writings, as flickers en route to revolution, or clinical diagnoses. Fanon's oeuvre and its readers generate a new critique of Yacine's canonical novel. This article develops absence as a new vocabulary, beyond colonial psychiatry and its agentive resistance, for the reading of literature from the settler colony. Building on feminist critiques of Nedjma, it names anti-Blackness in the novel as an instance of the text's participation in the field of Man at the moment it tries to write, through absence, its outside.
Quality of life in patients with temporomandibular joint arthrosis and orthopedic treatment of missing teeth depending on the severity of arthrosis and implant volume
Authors: Balykov V. , Shakhnovskyi I. , Burdeinyi V. , Cherednychenko A. , Lysenko V. , Nazarov O. , Rozhko P. 
Published: August 2024

Temporomandibular (TMJ) arthrosis severely impacts everyday activity and has substantial negative consequences for the general health state, especially when local manifestations are orchestrated by pronounced pain syndrome. That justifies the necessity of investigating the quality of life (QL) of patients with TMJ arthrosis who are undergoing orthopedic treatment. The research aimed to investigate the QL of patients with unilateral and bilateral TMJ arthrosis before and 6-8 months after occlusion correction, which was achieved by placing a different number of implants. In total, 127 patients (75 women and 52 men) were observed in the study of quality of life indicators, which were divided into four groups: bilateral TMJ arthrosis with the implantation of 3-6 implants (36 patients); bilateral TMJ arthrosis with the implantation of 1-2 implants (30 patients); unilateral TMJ arthrosis with the implantation of 3-6 implants (29 patients); unilateral TMJ arthrosis with the implantation of 1-2 implants (32 patients). Each group was comparable in age, gender, duration, and manifestations of arthrosis. QL was measured using questionnaire SF-36. In patients who were diagnosed with bilateral TMJ arthrosis and underwent implantation of 3-6 implants in the postponed period, only pain (P) and SRF scales significantly exceeded initial values – by two times and by 23.2% correspondently (P<0.05). In patients with bilateral TMJ arthrosis and implantation of 1-2 implants showed significant increase on all scales except PF and MH. Thus, the implantation of a significant number of implants (3-6) in the setting of unilateral manifestations of TMJ arthrosis showed an improvement in the quality of life of patients compared to the baseline level on five scales - PF, P, Vit, SRF and RLEH (P<0.05). In patients with unilateral TMJ arthrosis and a small number (1-2) of implant insertions, initial QL was relatively better when compared with other groups, and posttreatment improvement was seen in all scales (P<0.05). The results indicated the effectiveness of improving the quality of life by correcting the occlusion using permanent implants in patients with manifestations of TMJ arthrosis. The severity of the therapeutic effect has an inversely proportional relationship with the severity of the manifestations of arthrosis and the amount of orthopedic care provided. The obtained results indicate the effectiveness of the SF-36 questionnaire in orthopedic patients with TMJ arthrosis and general distinct health disorders.
The complicated relationship between asthma and swimming
Authors: Czarnecka Karolina , Burda Katarzyna , Korczak Anna , Szewczyk Oliwia , Olek Ewa , Jędrzejczyk Justyna , Łopacińska Olga , Stańczyk Katarzyna , Korn Aleksandra , Wójcik Emilia 
Published: August 2024

Introduction: Apart from pharmacological treatment, non-pharmacological strategies including physical activity play a significant role in the management of asthma. The aim of this paper is to examine various topics related to swimming and asthma. They include the detailed effect of swimming on asthma control,the potential role of swimming in early childhood asthma development, exercise induced asthma in swimmers as well as the relationship between asthma and cold water swimming.
Review methods: This article is based on the literature found in the PubMed Database from the period of 1971-2024 with the use of keywords such as “asthma”, “swimming”, “cold water swimming”, “exercise induced asthma”, “childhood asthma”
Description of the state of knowledge: Swimming is a safe form of physical activity for asthma patients.Swimming training enhances aerobic capacity, reduces exercise-induced bronchoconstriction and improves lung function in both pediatric and adult patients. However, there is a concern regarding indoor swimming pools that chlorine can potentially induce airway inflammation. There is research suggesting that early life swimming pool exposure may contribute to the asthma development in atopic children. There is some premise to the thought that cold water swimming may help alleviate asthma symptoms, but it also carries many risks.Swimming is a major cause of exercise induced asthma in professional athletes.
Conclusions: Alongside appropriate pharmacological treatment, swimming is a valuable strategy in asthma management in both pediatric and adult asthma patients. The risks of chlorinating pools are still not known to outweigh the benefits of swimming for asthmatics. Further research should be carried out on safety of early swimming in atopic children. Cold water swimming should also be evaluated in terms of safety and potential benefits for asthma patients.
Opportunistic Change During a Punctuation: How and When the Front Lines Can Drive Bursts of Incremental Change
Authors: Yang Elisabeth , DiBenigno Julia 
Published: August 2024

Environmental jolts can trigger more conducive conditions for driving change in organizations. However, punctuated equilibrium theories of organizational change concentrate on top managers’ implementation of de novo radical changes after jolts. Existing research has not examined frontline-driven, incremental change efforts during these periods of disrupted stasis, despite the value of frontline change ideas. We develop a process model to explain how and when those on an organization’s front lines can leverage a jolt to opportunistically implement long-desired change ideas in ways that promote their retention. We conducted a two-year qualitative field study at a hospital during the Covid-19 pandemic, examining the trajectories of 33 premeditated change ideas raised by frontline staff. By comparing ideas that persisted to become part of normal operations with those that failed to be selected or retained, we identified practices and conditions that promoted the selection and retention of frontline change ideas. Our study suggests that frontline change advocates can seed the long-term retention of “shovel-ready” ideas—as opposed to de novo ideas—after a jolt by rapidly and opportunistically deploying a novel set of practices before the brief window of opportunity created by lessened constraints and increased managerial receptivity closes. Prior theories of change largely assume frontline-driven change to be slow and continuous, proceeding in a one-off fashion; we explain how and when frontline change can instead occur in rapid, opportunistic bursts. This study advances theories of punctuated equilibrium and bottom-up change in organizations by unearthing an alternative way that change can be intentionally accomplished in organizations. Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2021.15120 .