bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apatinib and camrelizumab plus hepatic arterial infusion with oxaliplatin and 5-fluorouracil vs. apatinib and camrelizumab as the first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A randomized multi-center clinical trial.
Authors: He MinKe , Du Zefeng , Lai Zhicheng , Kan Anna , Shi Ming 
Published: July 2024

TPS4194 Background: The combination of immune checkpoint inhibitors and antiangiogenic drugs has been approved as the first-line treatment for advanced hepatocellular carcinoma (HCC). However, the survival benefit is still limited, especially in patients with high-risk features (Vp4, and/or bile duct invasion and/or tumor occupancy of ≥50% of the liver). Hepatic arterial infusion chemotherapy (HAIC) plus apatinib (an antiangiogenic drug) and camrelizumab (a PD-1 antibody) showed encouraging antitumor activity for these patients in a previous phase 2 study. Herein, we investigated the efficacy and safety of apatinib and camrelizumab plus HAIC compared with apatinib and camrelizumab as the first-line treatment for HCC with portal vein tumor thrombus (PVTT). Methods: In this randomized, open-label, phase 3 trial, eligible patients are ≥18 years with HCC confirmed by radiology, histology, or cytology. Other eligibility criteria were as follows: with PVTT, ECOG PS 0/1, no history of systemic therapy, not amenable to curative treatment approach, Child-Pugh A class liver score, and ≥1 measurable lesion by RECIST v1.1. A total of 214 patients (anticipated) will be randomized (1:1) to receive apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) plus HAIC with FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 20 hours via hepatic artery Q4W) or apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) until disease progression or intolerable toxicity. Stratification will be by patients with or without high-risk features. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, objective response rate per RECIST 1.1 and mRECIST, disease control rate per RECIST 1.1 and mRECIST, time to progression, duration of response, time to response, and safety. Whole-Exome Sequencing and RNA Sequencing of tumor biopsy samples were performed for predictive biomarker exploration. Clinical trial information: NCT05198609 .
Phase 1 study to evaluate safety and preliminary efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in patients with locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC).
Authors: Abi-Jaoudeh Nadine , Valerin Jennifer Brooke , Imagawa David K , Preise Dina , Sacks Zachary , Cohen Yaniv , Rothman Julia , Brook Keren , Morag Eyal , Scherz Avigdor Joshua , Krasnopolskaya Inna , Alpert Genia , Chung Vincent , Melstrom Laleh Golkar , Kessler Jonathan 
Published: July 2024

TPS4204 Background: Pancreatic cancer is the third most common cause of cancer death. Surgery offers the best survival rates however only a minority of patients are eligible. Approximately 15-20% of patients are deemed unresectable due to vascular involvement LA. Conversion of unresectable tumors, due to vascular involvement to resectable, is an unmet clinical need. Methods: A novel approach was developed to destroy the tumor encasing the artery combining padeliporfin, a photosensitive drug, locally activated by laser light illumination. The effectiveness of the strategy was confirmed in an orthotopic mouse model. A proof-of-concept study using 12 non-tumor pigs demonstrated an acceptable safety profile. A phase I dose escalation trial (NCT5918783) will be performed to evaluate the safety and maximal tolerated dose (MTD) of laser light dose of padeliporfin VTP. VTP will be delivered through an endovascular fiber integrated in a standard angioplasty balloon. The balloon will be advanced under fluoroscopy to the encased vascular segment of the superior mesenteric artery (SMA) and inflated. Following IV administration of padeliporfin, it will be activated by the laser light. Part A will be a classic 3+3 dose-escalation design to determine the MTD of laser light. The identified MTD will be applied in the Part B for preliminary efficacy evaluation. The primary objectives are to determine safety and MTD and/or recommended phase 2 laser light dose of VTP treatment. Secondary objectives are: rate of surgical conversion; evaluation of the pattern of disease progression (local regional and/or metastatic disease) after VTP based on CT. Standard of care surgery can be performed after 14 days post VTP. Key inclusion criteria: patients with histologically/cytologically confirmed stage III unresectable LA-PDAC in the head/uncinate process of the pancreas, with SMA solid tumor contact ˃180° with measurable disease per RECIST 1.1 and ECOG 0-1. Key exclusion criteria: metastatic disease, other malignancy, photosensitive skin diseases or porphyria, concurrent investigational therapy within past 30 days, medically uncontrolled moderate or severe ascites, previous radiation to pancreas, SMA variants. Recruitment begins in April 2024. Conversion of unresectable locally advanced pancreatic cancer to surgery is a critical unmet need. This phase I trial explores a novel approach to treat the tumor encasement enabling surgery. Clinical trial information: NCT5918783 .
Randomized pilot study assessing the safety and tolerability hyperthermic intraperitoneal chemotherapy (HIPEC) at completion of interval cytoreductive surgery or chemotherapy the day prior to interval cytoreductive surgery for patients with stage III/IV ovarian cancer undergoing neoadjuvant chemotherapy.
Authors: Backes Floor Jenniskens , Calo Corinne , Chambers Laura 
Published: July 2024

TPS5638 Background: A recent randomized phase III trial demonstrated an improvement in recurrence free and overall survival when heated intraperitoneal chemotherapy (HIPEC) was given at the time of interval cytoreductive surgery (iCRS) for advanced ovarian cancer. While there is rationale for HIPEC’s mechanism of effect, it remains unclear whether the observed benefit is because the chemotherapy schedule is not interrupted perioperatively (typically at least 6-8 weeks). We hypothesize that administration of the same agent and similar dose the day before surgery, will not increase toxicity and may improve feasibility for closing the gap between treatment cycles, while also limiting length of surgery and time under anesthesia. The primary objective of this study is to assess the feasibility, safety, and tolerability of IV Cisplatin the day prior to iCRS compared to HIPEC to determine if this is an acceptable alternative. Methods: This is a single institution randomized Pilot Study (NCT05415709). Patients with newly diagnosed stage III or IV epithelial (serous, mucinous, or endometrioid) ovarian, fallopian tube, or peritoneal cancer are eligible if they achieve a partial or complete response to 3-4 cycles of neoadjuvant carboplatin/paclitaxel +/- bevacizumab and are deemed to have disease amenable to a complete or optimal iCRS. Patients are scheduled for iCRS within 3-4 weeks following the third or fourth cycle and randomized 1:1 to IV Cisplatin (75 mg/m2) given the day prior to iCRS or HIPEC with Cisplatin (100 mg/m2) given intraoperatively over 90 min at 40°Celsius at the completion of surgical debulking. 15 patient per arm are planned (N=30); currently 7 patients have completed study interventions. No formal power calculation was required for this feasibility and safety study. Frequency and severity of adverse events (AEs) and tolerability of the regimens will be collected and summarized by descriptive statistics for each group. Patients who are able to receive planned treatment will be summarized as percentage for each treatment group. Accrual is anticipated to complete in June 2025. As an exploratory secondary endpoint, we plan to explore changes to the gut microbiome before and after HIPEC and examine correlative patterns with response and toxicity. Clinical trial information: NCT05415709 .
Biomarker-driven radiation therapy dose reduction after transoral robotic surgery for the treatment of HPV-positive oropharyngeal cancer.
Authors: Bates James Edward , Stokes William A. , McDonald Mark William , Rudra Soumon , Stallings Madison Miller , Lockney Natalie A , Mannion Kyle , Saba Nabil F. , Schmitt Nicole C. , Gross Jennifer H , Steuer Conor Ernst , Kaka Azeem , Topf Michael , Patel Mihir R. 
Published: July 2024

TPS6119 Background: HPV-related oropharyngeal squamous cell carcinoma (OPSCC) is a highly curable cancer with a considerable burden of treatment-related toxicities. Transoral surgery (TOS) is a treatment option for patients with early-stage disease; however, adjuvant radiotherapy (RT) is often recommended and can add to these late toxicities. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive marker of tumor recurrence, and undetectable post-operative ctHPVDNA is associated with improved recurrence-free survival. We hypothesize that patients with undetectable post-TOS ctHPVDNA without high risk pathologic factors can safely undergo de-escalation of adjuvant RT to 36 Gy, and this reduction will improve long-term swallowing function. Methods: We opened a multi-institutional phase II study (NCT05387915) including patients with pT1-2, N0-1, M0 HPV-related OPSCC who had TOS resection of their primary site and at least ipsilateral neck dissection. Pertinent inclusion criteria include a <10 pack-year smoking history, or a <30 pack-year smoking history if >10 years since last tobacco consumption, and pathologic findings of one or more intermediate risk factors: close margin (1 – 4 mm), perineural invasion, 2 – 4 positive lymph nodes or a single lymph node >3 cm. Patients with high risk factors (positive margin, extranodal extension, 5 or more positive lymph nodes) are excluded. Patients must have a detectable pre-operative ctHPVDNA and a post-operative ctHPVDNA drawn 7-14 days after TOS; if negative, patients receive 36 Gy of adjuvant RT in 15 fractions of 2.4 Gy delivered daily; if positive, they receive care per the discretion of the treating radiation oncologist. If the final surgical margins at the site of the primary tumor are >2mm, patients are eligible for omission of the primary tumor post-operative bed from the radiation volume. Our primary endpoint is 1-year swallowing function as measured by the composite MD Anderson Dysphagia Index (MDADI) score. Secondary endpoints include overall/progression-free survival and other quality of life metrics. The study is powered to detect an 8.5-point improvement in MDADI composite score at one year over the historical control from ECOG 3311 Arm B. With an alpha of 0.05 and a power of 0.90 we require 27 evaluable patients. Accounting for dropout and patients lost to follow-up, we aim to enroll 35 total patients. Since accrual began in June 2022, we have enrolled 18 patients as of January 2024. We recently opened the study at a second institution and are in the process of opening at a third institution. Clinical trial information: NCT05387915 .
HERD: A multi-centre prospective cohort study to facilitate early detection of relapse in radically treated, high risk head and neck squamous cell carcinoma.
Authors: Forster Martin , Mithra Sanjena , Ng Tony , Rosenfeld Nitzan , Sawyer Elinor , Reis Ferreira Miguel , Sinkus Ralph , Shmueli Karin , Coolen Ton , Roshan Amit , Mustapha Rami , Ng Kenrick , Gomes Camila , Petkar Imran , Guerrero Urbano Teresa , Connor Steve , Arora Asit , Fry Alastair , Berin Michelle , Brew-Graves Chris 
Published: July 2024

TPS6128 Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is the 7th most common cancer worldwide with more than 660,000 cases diagnosed annually. Many patients present with locally advanced disease, which despite aggressive multi-modality treatment remains associated with poor survival. Approximately 50% of patients relapse within 2 years, mostly occurring in the first year after treatment. Biomarkers predicting relapse are lacking and there remains no consensus on surveillance, with strategies differing according to local guidelines and recurrence too often detected when not amenable to salvage surgery (estimated to improve survival outcomes in relapsed HNSCC by up to 73%). We hypothesize that risk of relapse relies on a dynamic interplay between the immune profile, tumor microenvironment (TME; elucidated by radiology and tissue-based laboratory imaging), genomic background and clinicopathological characteristics. Our primary objectives are to develop and validate a multi-analyte based risk prediction tool and risk-stratified follow up strategy to enhance detection of early relapse and improve survival. Methods: This multi-center study is prospectively collectingsamples across multiple platforms including imaging, blood, saliva, stool, urine, and tissue from patients with newly diagnosed high risk locally advanced HPV-negative HNSCC planned for radical treatment (either surgery or (chemo)radiotherapy). We aim to recruit 200 patients in 2 stages, including discovery and validation cohorts. Three mechanistic (hypothesis-driven) meta-covariates and five working platform meta-covariates will be analysed to test recurrence prediction. Each meta-covariate represents an integrated risk score from covariate subsets. The 3 hypotheses are H1) combining magnetic resonance parameters of hypoxia and stromal composition with TME changes; H2) capturing the interactions between genomic mutations, immune cells and exosomes within the TME H3) understanding the relationship between micro-organisms and TME. The technical platforms include exosomal analyses, multi-parametric MRI including novel elastography (MRE) and quantitative magnetic susceptibility mapping (QSM) techniques, comprehensive circulating tumour and cell-free DNA analyses to aid detection of minimally residual disease, tissue immune profiling, somatic mutation testing and microbiome analysis. Regression Analysis will be performed by machine-learning with advanced mathematical and Bayesian statistical modelling. Accrual began in October 2023. Clinical trial information: NCT05097625 .
Improved water supply infrastructure to reduce acute diarrhoeal diseases and cholera in Uvira, Democratic Republic of the Congo: Results and lessons learned from a pragmatic trial
Authors: Gallandat Karin , Macdougall Amy , Jeandron Aurélie , Mufitini Saidi Jaime , Bashige Rumedeka Baron , Malembaka Espoir Bwenge , Azman Andrew S. , Bompangue Didier , Cousens Simon , Allen Elizabeth , Cumming Oliver 
Published: July 2024

Background
Safely managed drinking water is critical to prevent diarrhoeal diseases, including cholera, but evidence on the effectiveness of piped water supply in reducing these diseases in low-income and complex emergency settings remains scarce.

Methods
We conducted a trial of water supply infrastructure improvements in Uvira (DRC). Our primary objective was to estimate the relationship between a composite index of water service quality and the monthly number of suspected cholera cases admitted to treatment facilities and, as a secondary analysis, the number of cases confirmed by rapid diagnostic tests. Other exposures included the quantity of supplied water and service continuity. We used Poisson generalised linear models with generalised estimating equations to estimate incidence rate ratios.

Findings
Associations between suspected cholera incidence and water service quality (RR 0·86, 95% CI 0·73–1·01), quantity (RR 0·80, 95% CI 0·62–1·02) and continuity (RR 0·81, 95% CI 0·77–0·86) were estimated. The magnitudes of the associations were similar between confirmed cholera incidence and water service quality (RR 0·84, 95% CI 0·73–0·97), quantity (RR 0·76, 95% CI 0·61–0·94) and continuity (RR 0·75, 95% CI 0·69–0·81). These results suggest that an additional 5 L/user/day or 1.2 hour per day of water production could reduce confirmed cholera by 24% (95% CI 6–39%) and 25% (95% CI 19–31%), respectively.

Interpretation
Ensuring a sufficient and continuous piped water supply may substantially reduce the burden of endemic cholera and diarrhoeal diseases but evaluating this rigorously is challenging. Pragmatic strategies are needed for public health research on complex interventions in protracted emergency settings.

Trial registration
The trial is registered in ClinicalTrials.gov ID NCT02928341. https://classic.clinicaltrials.gov/ct2/show/NCT02928341.
Prevalence and transmission of the most relevant zoonotic and vector-borne pathogens in the Yucatan peninsula: A review
Authors: Sánchez-Soto Ma. Fernanda , Gaona Osiris , Vigueras-Galván Ana Laura , Suzán Gerardo , Falcón Luisa I. , Vázquez-Domínguez Ella 
Published: July 2024

Background
Habitat modification and land use changes impact ecological interactions and alter the relationships between humans and nature. Mexico has experienced significant landscape modifications at the local and regional scales, with negative effects on forest cover and biological biodiversity, especially in the Yucatan peninsula in southeastern Mexico. Given the close relationship between landscape modification and the transmission of zoonotic and vector-borne diseases, it is essential to develop criteria for identifying priority zoonoses in the south of the country.

Methodology/Principal findings
We reviewed 165 published studies on zoonotic and vector-borne diseases in the region (2015–2024). We identified the most frequent vectors, reservoirs, and hosts, the most prevalent infections, and the factors associated with transmission risk and the anthropogenic landscape modification in urban, rural, ecotone, and sylvatic habitats. The most relevant pathogens of zoonotic risk included Trypanosoma cruzi, arboviruses, Leishmania, Rickettsia, Leptospira, and Toxoplasma gondii. Trypanosoma cruzi was the vector-borne agent with the largest number of infected vertebrate species across habitats, while Leishmania and arboviruses were the ones that affected the greatest number of people. Dogs, cats, backyard animals, and their hematophagous ectoparasites are the most likely species maintaining the transmission cycles in human settlements, while rodents, opossums, bats, and other synanthropic animals facilitate connection and transmission cycles between forested habitats with human-modified landscapes. Pathogens displayed different prevalences between the landscapes, T. cruzi, arbovirus, and Leptospira infections were the most prevalent in urban and rural settlements, whereas Leishmania and Rickettsia had similar prevalence across habitats, likely due to the diversity and abundance of the infected vectors involved. The prevalence of T. gondii and Leptospira spp. may reflect poor hygiene conditions. Additionally, results suggest that prevalence of zoonotic and vector-borne diseases is higher in deforested areas and agricultural aggregates, and in sites with precarious health and infrastructure services.

Conclusions
Some hosts, vectors, and transmission trends of zoonotic and vector-borne diseases in the YP are well known but others remain poorly recognized. It is imperative to reinforce practices aimed at increasing the knowledge, monitoring, prevention, and control of these diseases at the regional level. We also emphasize the need to perform studies on a larger spatio-temporal scale under the socio-ecosystem perspective, to better elucidate the interactions between pathogens, hosts, vectors, environment, and sociocultural and economic aspects in this and many other tropical regions.
Statistical characteristics of analytical studies published in Peruvian medical journals from 2021 to 2022: A methodological study
Authors: Nombera-Aznaran Natalia , Guevara-Lazo David , Fernandez-Guzman Daniel , Taype-Rondán Alvaro 
Published: July 2024

Objective
While statistical analysis plays a crucial role in medical science, some published studies might have utilized suboptimal analysis methods, potentially undermining the credibility of their findings. Critically appraising analytical approaches can help elevate the standard of evidence and ensure clinicians and other stakeholders have trustworthy results on which to base decisions. The aim of the present study was to examine the statistical characteristics of original articles published in Peruvian medical journals in 2021–2022.

Design and setting
We performed a methodological study of articles published between 2021 and 2022 from nine medical journals indexed in SciELO-Peru, Scopus, and Medline. We included original articles that conducted analytical analyses (i.e., association between variables). The statistical variables assessed were: statistical software used for analysis, sample size, and statistical methods employed (measures of effect), controlling for confounders, and the method employed for confounder control or epidemiological approaches.

Results
We included 313 articles (ranging from 11 to 77 across journals), of which 67.7% were cross-sectional studies. While 90.7% of articles specified the statistical software used, 78.3% omitted details on sample size calculation. Descriptive and bivariate statistics were commonly employed, whereas measures of association were less common. Only 13.4% of articles (ranging from 0% to 39% across journals) presented measures of effect controlling for confounding and explained the criteria for selecting such confounders.

Conclusion
This study revealed important statistical deficiencies within analytical studies published in Peruvian journals, including inadequate reporting of sample sizes, absence of measures of association and confounding control, and suboptimal explanations regarding the methodologies employed for adjusted analyses. These findings highlight the need for better statistical reporting and researcher-editor collaboration to improve the quality of research production and dissemination in Peruvian journals.
Antimicrobial and Antioxidant Activities of Sesquiterpenes-Rich Essential Oil of Trichilia monadelpha (Thonn) J.J. De Wilde of Root Bark
Authors: Odeja Oluwakayode Olubunmi , Onocha Patricia A. , Oloyede Ganiyat Kehinde , Ayoyerokun Damola , Ibok Michael Gabriel , Okpala Ejike Onwudiegwu 
Published: July 2024

Trichilia monadelpha (Thonn) J.J. De Wilde (Meliaceae) is used in traditional medicine for the treatment of ulcers, cough and inflammatory disorders such as arthritis. In this present study, the essential oil of T. monadelpha root bark was obtained by hydrodistillation using an all-glass Clevenger apparatus. The identification and characterisation were done using Gas Chromatography-Mass Spectrometry. We also, aimed to evaluate the antimicrobial activity of the essential oil against ten micro-organisms using the Agar diffusion method and the free radical scavenging capacity was determined using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) methods. Twenty (20) different compounds made up the hydrodistilled essential oil, which made up 99.0% of the entire oil content. Sesquiterpene compounds made up about 73.3% of the essential oil from the root bark of T. monadelpha, which was described as sesquiterpenes-rich. Sesquiterpenes' most abundant constituents include (E)-Longipinene (18%), 10s,11s-Himachala-3-(12),4-diene (15.26%), Aromadendrene (11.12%), Alloaromadendrene oxide-(1) (8.82%), and β-Caryophyllene (5.92%). The essential oil inhibited growth against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aerugunosa, Candida albicans, Aspergillus niger, Klebsiella Pneumonia and Salmonella typhi at concentrations of 200 mg/mL to 50 mg/mL with an inhibitory zone of 20 – 10 mm while the antioxidant analysis of the essential oil revealed low scavenging activity which reveals that the synthetic antioxidants were more effective with an Ascorbic acid; IC50 value of 1.47 mgmL-1, Butyl hydroxyanisole; 1.88 mgmL-1, α-Tocopherol; 4.83 mgmL-1 followed by the essential oil with an IC50 value of 9.95 mgmL-1. T. monadelpha root bark essential oil contains notable chemical compounds that are responsible for its antioxidant and antimicrobial activities.