bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective trial to evaluate the performance of the multitarget hepatocellular carcinoma blood test (mt-HBT) for screening at-risk patients: The Altus study.
Authors: John Binu , Porter Kyle , Dahman Bassam , Parikh Neehar , Silva Alvin C. , Yang Ju Dong , Joseph Patrick , Strong Laura E. , Limburg Paul J. 
Published: January 2022

TPS486 Background: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death in the U.S. HCC surveillance is associated with improved early detection and receipt of curative treatment. However, current surveillance strategies suffer from low adherence and suboptimal sensitivity. The multi-target HCC blood test (mt-HBT) is a novel early detection assay that provides a qualitative result based on a multiparametric algorithm that incorporates information from methylation markers ( HOXA1, TSPYL5, and B3GALT6), AFP, and patient sex. Here, we describe the protocol for a prospective, multicenter clinical trial designed to investigate the performance of the mt-HBT in patients at risk for HCC. Methods: ALTernative to U/S (ALTUS) is a longitudinal, multicenter, prospective study with a targeted enrollment of 3,000 participants. The main inclusion and exclusion criteria are described in the table. Participants will receive HCC surveillance imaging (either U/S or CT/MRI) and blood collection for the mt-HBT. Those with positive U/S are anticipated to receive standard-of-care imaging follow-up with a multiphase CT or MRI, and those with a negative U/S will receive a study CT/MRI within 30 days of blood collection. Imaging interpretation is based on the CT/MRI LI-RADS (LR) v2018 categories. The primary endpoints are the overall sensitivity and specificity of the mt-HBT to detect HCC, defined as pathology-confirmed HCC or hepatocellular cholangiocarcinoma (cHCC-CCA), LR-4/5, or LR-TIV/M plus definite/probable HCC or cHCC-CCA. The secondary endpoints are mt-HBT early-stage sensitivity, and performance in a) participants with LR-5 or biopsy-confirmed HCC and b) participants confirmed non-HCC. Participants not diagnosed with a liver malignancy at visit one will continue to receive HCC surveillance, returning for a second visit ̃6 months from first blood collection. Blood will be collected after the second visit for the mt-HBT. Data on treatment will be collected for those diagnosed with HCC. Study participants and providers will be blinded to the mt-HBT results. Participants are currently enrolling across the U.S., with 60 targeted sites and an anticipated 12-month enrollment window. Clinical trial information: NCT05064553. [Table: see text]
Randomized, parallel arm, phase II study of telotristat (Xermelo) in combination with lutetium Lu 177 dotatate (Lutathera) in well-differentiated neuroendocrine tumors (NETs).
Authors: Chauhan Aman , Kunos Charles , Yan Donglin , Khurana Aman , Khouli Riham , Cavnar Michael J. , Pandalai Prakash , Kim Joseph , Anthony Lowell Brian 
Published: January 2022

TPS516 Background: PRRT using Lutetium Lu 177 Dotatate, has been approved by the FDA for metastatic, progressive gastroenteropancreatic neuroendocrine tumors (GEPNETs). Despite an impressive progression-free survival noted in NETTER-1 study, most patients will eventually progress after PRRT treatment. Increased serotonin secretion is found in a number of slow-growing NETs of the diffuse neuroendocrine system. Serotonin stimulates proliferation in cell lines of a typical (NCI-H727), an atypical (NCI-H720) bronchopulmonary NET, a small intestinal NET (KRJ-I), and a functioning human pancreatic carcinoid cell line (BON). This stimulation of growth by serotonin can be performed in an autocrine manner. Telotristat ethyl is a novel oral inhibitor of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis. In 2017, results of placebo-controlled phase III study (Telestar) evaluating Telotristat ethyl confirmed that among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with Telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in bowel movement frequency and urinary 5- hydroxy indoleacetic acid (u5-HIAA). Based on results of the Telestar trial, FDA approved 250 mg PO TID dosage of Telotristat for control of carcinoid syndrome diarrhea. Of note, 500 mg TID arm showed increased decline in urinary 5-HIAA as compared to 250 mg TID arm. Study Hypotheses: We hypothesize that inhibition of serotonin production will lead to cytostatic effect on neuroendocrine tumors and will complement anti-tumor activity of lutetium 177 dotatate. We anticipate our proposed combination will result in improved treatment efficacy as reflected by improved 20-month PFS as compared to historical control (NETTER-1). Methods: This is a single center, open label, randomized, parallel arm, phase II study evaluating two dose levels of Telotristat (Xermelo; 250 mg vs 500 mg) in combination with Lutetium Lu 177 Dotatate (Lutathera) in 70 well-differentiated neuroendocrine tumor patients. Study is currently enrolling patients and is expected to complete accrual in 3 years. Clinical trial information: NCT04543955.
A multi-institutional, single-arm, phase II trial of neoadjuvant modified-FOLFIRINOX for resectable pancreatic ductal adenocarcinoma.
Authors: Lee Choong-kun , Hwang Ho Kyoung , Jeung Hei-Cheul , Chon Hongjae , Park Hyung Soon , Kim Min Hwan , Park Mi-Suk , Kang Chang Moo , Choi Hye Jin 
Published: January 2022

TPS624 Background: Within the next decade, pancreatic ductal adenocarcinoma (PDAC) is expected to rise to the second leading cause of cancer-related mortality. To increase the survival, various peri-operative treatments have been tested, and adjuvant FOLFIRINOX or gemcitabine plus capecitabine is now standard of care after surgical resection for localized PDAC. Even with superior survival among various disease extent of PDAC, resectable PDAC still shows poor outcomes with surgery followed by adjuvant chemotherapy. This phase II study is investigating the role of modified-FOLFIRINOX as neoadjuvant treatment for resectable PDAC. Methods: This study is a phase II, multi-institutional, single-arm trial to evaluate the efficacy and safety of modified-FOLFIRINOX in resectable PDAC. The main inclusion criteria are histologically confirmed PDAC; resectable PDAC confirmed by both computed tomography (CT) and magnetic resonance imaging (MRI) according to NCCN guideline resectability criteria (no arterial tumor contact to celiac axis, SMA or CHA; no tumor contact with SMV or PV or ≤180° contact without vein contour irregularity); no previous treatment (surgery or chemotherapy); ECOG 0 or 1; and adequate organ function. Patients receive oxaliplatin 85 mg/m2 D1 + leucovorin 400mg/m2 D1 + irinotecan 150 mg/m2 D1 + 5-FU 2,000 mg/m2 46h continuous infusion, every other week for 6 cycles (12 weeks). Response assessments are performed every 6 weeks using the RECIST criteria version 1.1. Baseline MRI, PET-CT scan before treatment, and pre-surgery MRI after 6 cycles are mandatory. The primary endpoint was R0 resection rate. Secondary endpoints included progression-free survival, overall survival, disease-free survival, objective response rate, safety, resection rate, and correlative biomarker exploration. The study will enroll up to 27 patients and is currently recruiting at four sites in South Korea. As of September 2021, 20 patients have been enrolled. Clinical trial information: KCT0004421 (Registration ongoing for clinicaltrials.gov).
A phase 1, first-in-human (FIH) study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in subjects with HER2 overexpressing solid tumors.
Authors: Reiss Kim Anna , Yuan Yuan , Barton Debora , Cushing Daniel , Ronczka Amy , Klichinsky Michael , Dees Elizabeth Claire 
Published: January 2022

TPS668 Background: Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but not in those with solid tumors. Macrophages are actively recruited into, and are abundantly present in the solid tumor microenvironment (sTME). Tumor- associated macrophages typically display immunosuppressive behavior, but when engineered to be proinflammatory, may be an ideal vector to administer adoptive cellular therapy in solid tumors. Furthermore, insertion of a CAR on the macrophages allow them to selectively recognize and phagocytose antigen overexpressing cancer cells. CAR macrophages reprogram the sTME and present neoantigens to T cells, leading to epitope spreading and immune memory. Human Epidermal Growth Factor Receptor 2 (HER2) overexpression promotes tumorigenesis in many cancers (Table). CT-0508 is a cell product comprised of autologous monocyte-derived pro-inflammatory macrophages expressing an anti-HER2 CAR. Pre-clinical studies have shown that CT-0508 induced targeted cancer cell phagocytosis while sparing normal cells, decreased tumor burden and prolonged survival in relevant models. CT-0508 cells were safe and effective in a semi-immunocompetent mouse model of human HER2 overexpressing ovarian cancer. Methods: This is a FIH Phase 1 study to evaluate safety, tolerability, cell manufacturing feasibility, trafficking and preliminary evidence of efficacy of investigational product CT-0508 in 18 subjects with locally advanced (unresectable) or metastatic solid tumors overexpressing HER2, who have failed available therapies, including anti-HER2 therapies when indicated. Filgrastim is being used to mobilize autologous hematopoietic progenitor cells for monocyte collection by apheresis. The CT-0508 CAR macrophage product is manufactured, prepared and cryopreserved from mobilized peripheral blood monocytes. Group 1 subjects receive CT-0508 infusion split over D1, 3 and 5. Dose limiting toxicities will be observed and addressed by a Safety Review Committee. Group 2 subjects will receive the full CT-0508 infusion on D1. Pre and post treatment biopsies and blood samples will be collected to investigate correlates of safety (immunogenicity), trafficking (PCR, RNA scope), CT-0508 persistence in blood and in the tumor, target antigen engagement, TME modulation (single cell RNA sequencing), immune response (TCR sequencing) and others. Clinical trial information: NCT04660929. [Table: see text]
Tractography-Based Surgical Targeting for Thalamic Deep Brain Stimulation: A Comparison of Probabilistic vs Deterministic Fiber Tracking of the Dentato-Rubro-Thalamic Tract
Authors: Yang Andrew I. , Parker Drew , Vijayakumari Anupa A. , Ramayya Ashwin G. , Donley-Fletcher Melanie P. , Aunapu Darien , Wolf Ronald L. , Baltuch Gordon H. , Verma Ragini 
Published: January 2022

BACKGROUND:
The ventral intermediate (VIM) thalamic nucleus is the main target for the surgical treatment of refractory tremor. Initial targeting traditionally relies on atlas-based stereotactic targeting formulas, which only minimally account for individual anatomy. Alternative approaches have been proposed, including direct targeting of the dentato-rubro-thalamic tract (DRTT), which, in clinical settings, is generally reconstructed with deterministic tracking. Whether more advanced probabilistic techniques are feasible on clinical-grade magnetic resonance acquisitions and lead to enhanced reconstructions is poorly understood.

OBJECTIVE:
To compare DRTT reconstructed with deterministic vs probabilistic tracking.

METHODS:
This is a retrospective study of 19 patients with essential tremor who underwent deep brain stimulation (DBS) with intraoperative neurophysiology and stimulation testing. We assessed the proximity of the DRTT to the DBS lead and to the active contact chosen based on clinical response.

RESULTS:
In the commissural plane, the deterministic DRTT was anterior (P < 10−4) and lateral (P < 10−4) to the DBS lead. By contrast, although the probabilistic DRTT was also anterior to the lead (P < 10−4), there was no difference in the mediolateral dimension (P = .5). Moreover, the 3-dimensional Euclidean distance from the active contact to the probabilistic DRTT was smaller vs the distance to the deterministic DRTT (3.32 ± 1.70 mm vs 5.01 ± 2.12 mm; P < 10−4).

CONCLUSION:
DRTT reconstructed with probabilistic fiber tracking was superior in spatial proximity to the physiology-guided DBS lead and to the empirically chosen active contact. These data inform strategies for surgical targeting of the VIM.
The association between the lymph node ratio, surgical margin, and survival in patients with colon cancer receiving adjuvant chemotherapy
Authors: Fidan Evren , Merev Elif , Usta Arif , Alandağ Celal , Dişli Şafak , Özdöver Ali 
Published: January 2022

Objectives: To investigate the prognostic significant of lymph node ratio and surgical margins in patients with colon cancer undergoing surgery.
Methods: This observational and retrospective study was conducted at Karadeniz Technical University Medical Faculty, between 1 January, 2010 and 31 November, 2020. A series of 137 patients who had undergone surgical resection of colon carcinoma were included in this study. mLNR, deﬁned as the ratio of the number of mLNs to the number of examined lymph nodes, was calculated in colorectal cancer cases with lymph node metastasis. Patients were divided into three groups; LNR1 (< 0.25), LNR2 (0.25-0.6) and LNR3 (> 0.6).
Results: Mean disease-free survival was 79.2 months (95% CI 71.0-87.4). The mean expected survival time was 73.5 months (95% CI: 65.9-81.0). As the metastatic LN ratio increased, the rate of local recurrence or distant metastasis increased statistically significantly (p=0.007). As the metastatic LN ratio increased, the death rate increased statistically significantly (p=0.036). Metastatic lymph node ratio did not have a statistically significant effect on overall survival in patients with stage-3 and more than 12 LNs removed (p=0.069). There was no statistically significant association between the closeness of the surgical margin and disease-free survival in stage 1 (p=0.505) and stage-2 (p=0.161). There was no statistically significant association between the closeness of the surgical margin and overall survival among patients with stage 1 (p=0.494) and stage 2 (p=0.265).
Conclusion: A high metastatic LNR is associated with poorer overall and disease-free survival.
doi: https://doi.org/10.12669/pjms.38.3.5085
How to cite this:Fidan E, Merev E, Usta A, Alandag C, Disli S, Ozdover A. The association between the lymph node ratio, surgical margin, and survival in patients with colon cancer receiving adjuvant chemotherapy. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.5085
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Posterior-Based Stopping Rules for Bayesian Ranking-and-Selection Procedures
Authors: Eckman David J. , Henderson Shane G. 
Published: January 2022

Sequential ranking-and-selection procedures deliver Bayesian guarantees by repeatedly computing a posterior quantity of interest—for example, the posterior probability of good selection or the posterior expected opportunity cost—and terminating when this quantity crosses some threshold. Computing these posterior quantities entails nontrivial numerical computation. Thus, rather than exactly check such posterior-based stopping rules, it is common practice to use cheaply computable bounds on the posterior quantity of interest, for example, those based on Bonferroni’s or Slepian’s inequalities. The result is a conservative procedure that samples more simulation replications than are necessary. We explore how the time spent simulating these additional replications might be better spent computing the posterior quantity of interest via numerical integration, with the potential for terminating the procedure sooner. To this end, we develop several methods for improving the computational efficiency of exactly checking the stopping rules. Simulation experiments demonstrate that the proposed methods can, in some instances, significantly reduce a procedure’s total sample size. We further show these savings can be attained with little added computational effort by making effective use of a Monte Carlo estimate of the posterior quantity of interest. Summary of Contribution: The widespread use of commercial simulation software in industry has made ranking-and-selection (R&S) algorithms an accessible simulation-optimization tool for operations research practitioners. This paper addresses computational aspects of R&S procedures delivering finite-time Bayesian statistical guarantees, primarily the decision of when to terminate sampling. Checking stopping rules entails computing or approximating posterior quantities of interest perceived as being computationally intensive to evaluate. The main results of this paper show that these quantities can be efficiently computed via numerical integration and can yield substantial savings in sampling relative to the prevailing approach of using conservative bounds. In addition to enhancing the performance of Bayesian R&S procedures, the results have the potential to advance other research in this space, including the development of more efficient allocation rules.
Local Density Estimation in High Dimensions
Authors: Wu Xian , Charikar Moses , Natchu Vishnu 
Published: January 2022

An important question that arises in the study of high-dimensional vector representations learned from data are, given a set [Formula: see text] of vectors and a query q, estimate the number of points within a specified distance threshold of q. We develop two estimators, LSH count and multiprobe count that use locality-sensitive hashing to preprocess the data to accurately and efficiently estimate the answers to such questions via importance sampling. A key innovation is the ability to maintain a small number of hash tables via preprocessing data structures and algorithms that sample from multiple buckets in each hash table. We give bounds on the space requirements and sample complexity of our schemes and demonstrate their effectiveness in experiments on a standard word embedding data set.
Can Racial Diversity Attenuate Racial Discrimination in Service Interactions? Evidence from Cite-and-Release Decisions within Police Departments
Authors: Meuris Jirs 
Published: January 2022

Despite the belief that racial diversity in organizations will attenuate racial discrimination in service interactions, the extant literature suggests that it may often exacerbate discrimination by generating intergroup conflict. In this paper, I propose that the influence of racial diversity on racial discrimination in service interactions will depend upon (a) the level of interdependence within an organization and (b) whether an increase in diversity consists of a larger representation of a minority’s own racial group. To test my predictions, I combine interaction-level data covering approximately 200,000 cite-and-release decisions where suspects are either given a summons to attend court at a later date or transported to jail following arrest with longitudinal organization-level data from 93 police departments across the United States. Consistent with prior research, I found that minority suspects were less likely to be cited and released for the same offense relative to White suspects. Racial diversity among sworn officers in a police department exacerbated discrimination in cite-and-release decisions unless officers’ work roles were highly interdependent due to the adoption of community-oriented policing. Focusing on Black and Hispanic suspects, I observed this pattern regardless of whether an increase in racial diversity in the department was characterized by a larger representation of a minority suspect’s own racial group or other minority racial groups. Taken together, the findings suggest that diverse organizations can mitigate the emergence of intergroup conflict that exacerbates racial discrimination in service interactions by fostering interdependencies. Supplemental Material: Data are available at https://doi.org/10.1287/orsc.2021.1571 .
Airway Assessment for Intravenous Sedation in Dentistry
Authors: Owen Brandon , Bradley Hannah 
Published: January 2022

The ability to manage an airway is an essential skill for the safe provision of intravenous conscious sedation. A systematic airway assessment will allow identification of risk factors pre-operatively, flagging potential airway problems and aiding case selection. If difficulties arise, the practitioner will be able to act efficiently having anticipated the risk factors. Importantly, cases unsuitable for primary care can be readily identified and referred appropriately. In the interest of patient safety, this article aims to present methods of airway assessment that can be incorporated into the pre-sedation assessment. CPD/Clinical Relevance: This article discusses airway assessment methods relevant to intravenous conscious sedation to promote patient safety.
Multidisciplinary management of a central giant cell lesion: a case report
Authors: Tajmehr Niecoo , Javidi Hanieh , Laugharne David , Smith Anne-Marie 
Published: January 2022

This case report describes the diagnosis and management of a central giant cell lesion in a young, healthy patient. The article outlines the differences between central giant cell lesions and their counterparts, peripheral giant cell lesions. More crucially, it highlights the challenge in distinguishing these lesions, which are almost identical histopathologically. CPD/Clinical Relevance: This case describes the difficulties that can be faced by clinicians in differentiating between peripheral giant cell lesions and central giant cell lesion. It also highlights the need for specialist multidisciplinary input in managing the surgical and orthodontic implications of these lesions.