bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of Minnelide and paclitaxel combination chemotherapy in refractory gastric cancer (GC).
Authors: Lee Jeeyun , Kim Seung Tae , Kang Won Ki , Saluja Ashok 
Published: February 2023

414 Background: Minnelide is a prodrug that rapidly releases the active compound triptolide when exposed to phosphatases in the bloodstream. Triptolide is a diterpene that has been shown to inhibit tumor cell proliferation and induce apoptosis in various cancer types. The anti-tumor effect of triptolide is the result of inhibition of heat shock protein (HSP) 70 expression. In GC Minnelide inhibits Sp1 to decrease HSP70 and induce cell death in preclinical data. Methods: This phase 1 trial was designed to determine the maximum tolerated dose (MTD) of Minnelide monotherapy and the MTD of Minnelide in combination with paclitaxel in refractory GC patients. There were 6 cohorts tested in this trial: cohort A: Minnelide 1 mg qd D1-21, q 28 days; cohort B: Minnelide 1.25 mg qd D1-21, q 28 days; cohort C: 1.5 mg qd D1-21, q 28 days; cohort D: Minnelide 0.25 mg D1-21 + weekly paclitaxel 60 mg/m2 on D1, D8, D15; cohort E: Minnelide 0.5 mg qd D1-21+ weekly paclitaxel 80 mg/m2 on D1, D8, D15; cohort F: Minnelide 0.75 mg qd D1-21+ weekly paclitaxel 80 mg/m2 D1, D8, D15. Results: From Feb 2021 to Sep 2022, 23 GC patients were enrolled (cohort A – C, N=10; cohort D-F, N=12). All patients had metastatic disease at the time of study enrollment. 20 of 23 patients received the study treatment as >= 3rd-line (range, 2 – 6th line). In all, 3 patients had HER2 positive GC and 10 patients had PDL1 + tumor. In the monotherapy cohorts, there were no DLTs observed, and the regimen was tolerated well. One patient achieved confirmed PR which lasted for 6 months. For the combination arm (cohort D-F), there were no DLTs observed. Of the 11 patients who were evaluable for treatment response, there were 1 PR, 5 SDs and 5 PDs. Two of five patients who achieved stable disease had durable stable disease for > 6 months on study treatment. In the combination cohorts, the most common adverse events of any grade were neutropenia; however, there was no neutropenic fever or treatment related mortality. Conclusions: Minnelide in combination with weekly paclitaxel demonstrated promising anti-tumor activity with durable responses in refractory AGC. Clinical trial information: Underreview .
Optimal perioperative therapy for incidental gallbladder cancer (OPT-IN): A randomized phase II/III trial—ECOG-ACRIN EA2197.
Authors: Maithel Shishir K. , Hong Sung Chul , Ethun Cecilia Grace , Ferrone Cristina R. , Rocha Flavio G. , Staley Charles A. , O'Dwyer Peter J. 
Published: February 2023

TPS620 Background: Gallbladder carcinoma (GBC) is a rare disease with a poor prognosis, with an overall estimated 5-year survival rate of 5-13%. Approximately 70% of gallbladder cancers in the US are found incidentally on pathologic analysis after elective cholecystectomy for presumed benign disease. Current management guidelines for incidental gallbladder cancer (IGBC) recommend re-resection for T1b, T2, and T3 lesions, which entails a partial hepatectomy and lymph node dissection. Up to 75% of patients have residual locoregional disease and 20% have disseminated disease at the time of re-resection, both factors strongly associated with poor prognosis and inoperability, respectively. For those who undergo re-resection, the recurrence rate at one year can be as high as 40%. Therefore we designed a Phase II/III trial to assess the benefit of a perioperative chemotherapy approach around the re-resection procedure compared to standard of care adjuvant therapy alone. Methods: We have enrolled 18 of 186 planned patients (Phase III design) on study NCT 04559139/EA2197. Current eligibility criteria include: Incidentally diagnosed T2 / T3 gallbladder cancer with no evidence of metastatic disease or inoperable locoregional disease. At randomization, patients must be within 12 weeks of their index cholecystectomy. Patients are randomized 2:1 to receive perioperative chemotherapy with gemcitabine and cisplatin vs adjuvant therapy alone. The primary endpoint is overall survival. Secondary endpoints include resectability, presence of residual disease, and progression-free survival. Clinical trial information: 04559139 .
The future of sickle cell disease therapeutics rests in genomics
Authors: Wonkam Ambroise 
Published: February 2023

ABSTRACT
Sickle cell disease (SCD) is the most-common monogenic recessive disease in humans, annually affecting almost 300,000 newborns worldwide, 75% of whom live in Africa. Genomics research can accelerate the development of curative therapies for SCD in three ways. First, research should explore the missing heritability of foetal haemoglobin (HbF) – the strongest known modifier of SCD clinical expression – among highly genetically heterogenous and understudied African populations, to provide novel therapeutics targets for HbF induction. Second, SCD research should invest in RNA therapies, either by using microRNA to target the production of HbF proteins by binding to the transcription machinery in a cell, or by directly mediating production of HbF or adult haemoglobin through injection of messenger RNA. Third, investigators should aim to identify currently unknown genetic risk factors for SCD cardiovascular complications, which will address mortality, particularly in adults. Now is the time for global research programs to uncover genomic keys to unlock SCD therapeutics.
In poetry, if meter has to help memory, it takes its time
Authors: Andreetta Sara , Soldatkina Oleksandra , Boboeva Vezha , Treves Alessandro 
Published: February 2023

To test the idea that poetic meter emerged as a cognitive schema to aid verbal memory, we focused on classical Italian poetry and on three components of meter: rhyme, accent, and verse length. Meaningless poems were generated by introducing prosody-invariant non-words into passages from Dante’s Divina Commedia and Ariosto’s Orlando Furioso. We then ablated rhymes, modified accent patterns, or altered the number of syllables. The resulting versions of each non-poem were presented to Italian native speakers, who were then asked to retrieve three target non-words. Surprisingly, we found that the integrity of Dante’s meter has no significant effect on memory performance. With Ariosto, instead, removing each component downgrades memory proportionally to its contribution to perceived metric plausibility. Counterintuitively, the fully metric versions required longer reaction times, implying that activating metric schemata involves a cognitive cost. Within schema theories, this finding provides evidence for high-level interactions between procedural and episodic memory.
Open Science Training in TRIPLE
Authors: Provost Lottie , Di Donato Francesca , Tóth-Czifra Erzsébet , Dumouchel Suzanne , Blotière Emilie , Chen Yin 
Published: February 2023

This case study focuses on the online training activities on Open Science delivered within the H2020 project Transforming Research through Innovative Practices for Linked Interdisciplinary Exploration (TRIPLE, Grant Agreement 863420). The project is dedicated to building a discovery platform for the Social Sciences and Humanities (SSH) and is committed to promoting and supporting the uptake of Open Science within research practices. In order to address SSH research and training communities’ needs for enhanced competencies on Open Science and for stronger support in the Findable, Accessible, Interoperable, Reusable (FAIR) management of digital training materials, two reusable outputs were produced. The work carried out is presented as a novel approach to tackle the issues related to FAIRifying research and training practices and to create training resources whose reusability and relevance reaches beyond the project lifetime and framework. The case study presents the methods by which the results were produced so as to encourage and enable their future adaptation and reuse. The TRIPLE Open Science training series (result 1) targets SSH researchers, research support personnel and infrastructure developers in need of practical tools and specific skills to integrate Open Science practices in their workflows. The training series provides 12 competence-oriented online training events in Open Access whose training materials are available as Open Educational Resources (OER). The TRIPLE Training Toolkit (result 2) targets training organisers and research performing organisations who wish to design and manage training events as OERs and increase the impact of their training following good practice. The Toolkit is an easily reproducible workflow designed to help trainers minimise the time they spend in managing training events following FAIR practice. The workflow follows a FAIR-by-design method to address the frequent findability and reusability issues related to the management of digital training resources.
DEVELOPMENT OF A PREDICTION MODEL (NZSPINE) FOR SIGNIFICANT ADVERSE OUTCOME AFTER SPINE SURGERY
Authors: Coia Jadresic M. , Baker J. 
Published: February 2023

Numerous prediction tools are available for estimating postoperative risk following spine surgery. External validation studies have shown mixed results. We present the development, validation, and comparative evaluation of novel tool (NZSpine) for modelling risk of complications within 30 days of spine surgery.Data was gathered retrospectively from medical records of patients who underwent spine surgery at Waikato Hospital between January 2019 and December 2020 (n = 488). Variables were selected a priori based on previous evidence and clinical judgement. Postoperative adverse events were classified objectively using the Comprehensive Complication Index. Models were constructed for the occurrence of any complication and significant complications (based on CCI >26). Performance and clinical utility of the novel model was compared against SpineSage (https://depts.washington.edu/spinersk/), an extant online tool which we have shown in unpublished work to be valid in our local population.Overall complication rate was 34%. In the multivariate model, higher age, increased surgical invasiveness and the presence of preoperative anemia were most strongly predictive of any postoperative complication (OR = 1.03, 1.09, 2.1 respectively, p <0.001), whereas the occurrence of a major postoperative complication (CCI >26) was most strongly associated with the presence of respiratory disease (OR = 2.82, p <0.001).Internal validation using the bootstrapped models showed the model was robust, with an AUC of 0.73. Using sensitivity analysis, 80% of the model's predictions were correct. By comparison SpineSage had an AUC of 0.71, and in decision curve analysis the novel model showed greater expected benefit at all thresholds of risk.NZSpine is a novel risk assessment tool for patients undergoing acute and elective spine surgery and may help inform clinicians and patients of their prognosis. Use of an objective tool may help to provide uniformity between DHBs when completing the “clinician assessment of risk” section of the national prioritization tool.
DOES PATIENT AGE INFLUENCE FUNCTIONAL OUTCOMES TWO YEARS AFTER PERIACETABULAR OSTEOTOMY?
Authors: Koo Y.E. , Lightfoot N.J. , Boyle M.J. 
Published: February 2023

The influence of patient age on functional outcomes after periacetabular osteotomy (PAO) for acetabular dysplasia remains unclear, with previous studies utilising scores developed for older, arthritic patients. The purpose of this study is to assess the influence of patient age on International Hip Outcome Tool (iHOT-12) scores, two years after PAO.Eighty-six patients (72 female, 14 male; mean age 26.9 years) who underwent PAO by a single surgeon and had completed a minimum of two years follow up were identified. Patients were categorised into three groups according to age at the time of surgery: adolescent (11-20 years; n=29), young adult (21–30 years; n=29), and mature (≥31 years; n=28). The three groups were compared with respect to baseline variables and functional outcomes (iHOT-12, EQ-5D quality of life score, University of California Los Angeles (UCLA) activity score, pain visual analogue score (VAS)). Multivariate regression was undertaken to assess for independent predictors of two-year iHOT-12 score.The adolescent group demonstrated a lower BMI (p=0.004) while the mature group had a greater American Society of Anaesthesiology (ASA) score (p=0.049). There were otherwise no significant differences in baseline variables between the three groups (all p>0.05).The three groups demonstrated significant post-operative improvements across all functional outcome measures. There were no significant differences in two-year iHOT-12, EQ-5D, UCLA score or pain VAS between the three groups (all p>0.05). Regression modelling found that patient age at the time of surgery did not have an independent effect on two-year iHOT-12 score (p=0.878).We found that patient age at the time of surgery did not influence functional outcomes two years after PAO. Our results suggest that patient age should not be considered in isolation as an indication or contraindication for PAO.
“RULES-BASED MOTION” REANIMATION OF THE CARPUS
Authors: Sandow MJ , Howard C , Cheng ZX 
Published: February 2023

Using a reverse engineering capability to quantify the factors that control the rigid body mechanics of the wrist, a mathematical forward animation capability and model of wrist motion that allows the carpus to move under its own rules is being developed. This characterises the isometric connections, from which was developed the Stable Central Column Theory of Carpal Mechanics - which incorporates the Law of Rules Based Motion.This work has now advanced to the ability to reapply the extracted rules to allow rules-based rigid body reanimation of an individual wrist. As each wrist is unique, there is a given reality that each reanimation must be based on an individual wrist's unique rules, and the aspiration to create a standard or normal wrist is unrealistic.Using True Life Anatomy (Adelaide, Aust) analysis software, the specific rules (morphology / connectivity / interaction / loading) of individual wrists have been characterised, and then reapplied in a rigid body reanimation environment using Adams (MSC Software, U.S.) software.In the preliminary application of this biomechanics environment, by using the reverse engineering / forward reanimation process, wrist motion can be recreated - based purely on the unique rules, extracted from individual wrists. Instability of the proximal scaphoid was evident in several of the animations, and there was confirmation that the spatial attachment points of the isometric constraints are very exacting. The actual attachment and specific morphology of the carpal bones varied between individual wrists.Using a reverse engineering and then forward reanimation process, we have been able to recreate wrist motion using the rigid body mechanics based on the Law of Rules Based Motion. Further work is required, but the potential to apply “what if” virtual surgery options to an individual injured wrist and more precisely characterise and test solutions to wrist dysfunction are becoming realised.
AVASCULAR NECROSIS RATES IN MODERATE TO SEVERE UNSTABLE SLIPPED CAPITAL FEMORAL EPIPHYSIS: ANTERIOR OPEN REDUCTION VERSUS THE MODIFIED DUNN PROCEDURE
Authors: St George J. , Norquay M. , Birke O. , Gibbons P. , Little D. 
Published: February 2023

The risk of AVN is high in Unstable Slipped Capital Femoral Epiphysis (SCFE) and the optimal surgical treatment remains controversial. Our AVN rates in severe, unstable SCFE remained unchanged following the introduction of the Modified Dunn Procedure (MDP) and as a result, our practice evolved towards performing an Anterior Open Reduction and Decompression (AOR) in an attempt to potentially reduce the “second hit” phenomenon that may contribute. The aim of this study was to determine the early surgical outcomes in Unstable SCFE following AOR compared to the MDP.All moderate to severe, Loder unstable SCFEs between 2008 and 2022 undergoing either an AOR or MDP were included. AVN was defined as a non-viable post-operative SPECT-CT scan.Eighteen patients who underwent AOR and 100 who underwent MPD were included. There was no significant difference in severity (mean PSA 64 vs 66 degrees, p = 0.641), or delay to surgery (p = 0.973) between each group. There was no significant difference in the AVN rate at 27.8% compared to 24% in the AOR and MDP groups respectively (p = 0.732). The mean operative time in the AOR group was 24 minutes less, however this was not statistically significant (p = 0.084). The post-reduction PSA was 26 degrees (range, 13-39) in the AOR group and 9 degrees (range, −7 to 29) in the MDP group (p<0.001). Intra-operative femoral head monitoring had a lower positive predictive value in the AOR group (71% compared to 90%).Preliminary results suggest the AVN rate is not significantly different following AOR. There is less of an associated learning curve with the AOR, but as anticipated, a less anatomical reduction was achieved in this group. We still feel that there is a role for the MDP in unstable slips with a larger remodelling component.
EFFECT OF PERIOPERATIVE VITAMIN C ON THE INCIDENCE OF COMPLEX REGIONAL PAIN SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Seth I. , Bulloch G. , Seth N. , Siu A. , Clayton S. , Lower K. , Roshan S. , Nara N. 
Published: February 2023

Complex regional pain syndrome type 1 (CRPS-I) is a devastating complication that can occur after limb extremity injuries. The effectiveness of vitamin C in preventing CRPS-I incidence is debatable. Therefore, we conducted a systematic review and meta-analysis to assess the role of vitamin C in CRPS-I prevention and its effect on pain score, functional outcomes and complications rate after wrist, ankle, and foot fractures.We searched Medline, Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar from infinity to May 2021 for relevant studies comparing the incidence of CRPS-I with administration of perioperative vitamin C versus placebo after wrist, ankle, and foot fractures. Continuous data such as functional outcomes and pain scores were pooled as mean differences (MD), whist dichotomous variables such as the incidence of CRPS-I and complications were pooled as odds ratios (OR), with 95% confidence interval (CI). Data analyses was done using R software (meta package, version 4.9-0) for Windows.Eight studies, including two quasi-experimental studies, were included. The timeframe for vitamin C administration ranged from 42 to 50 days post-injury and/or surgical fixation and the dosage was either 500 mg or 1000 mg. The results showed that vitamin C was associated with a lower rate of CRPS-I relative to a placebo (OR 0.33, 95% CI [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (OR 1.90, 95% CI [0.99, 3.65]), functional outcomes (MD 6.37, 95% CI [-1.40, 14.15]), and pain scores (MD −0.14, 95% CI [-1.07, 0.79]).The findings demonstrate that when compared to placebo, at least 42 days of vitamin C prophylaxis is associated with prevention of CRPS-I following wrist, ankle, and foot fractures, irrespective of vitamin C dosage or fracture type. No significant differences were found with secondary outcomes.
FIRST RIB FRACTURE: STILL A MARKER OF TRAUMA SEVERITY?
Authors: Flaaten N. , Dyke G. 
Published: February 2023

First rib fractures (FRFs) have historically been a marker for severe trauma and poor outcomes. The aim of this study was to assess whether an association still exists between a fractured first rib and global trauma scores suffered by the patient, examine mortality rate and identify other commonly associated injuries.This study examined patients who presented to the Rockhampton Hospital with a traumatic FRF between the dates of July 2015 to June 2020. Patient demographics, mortality rate and additional injuries sustained by the patients were collected. The Injury Severity Score (ISS) was utilised and calculated for each patient. Analysis was conducted to determine associations between trauma scores and FRFs, mortality rate and other injuries sustained at the time of rib fracture.In total, 545 patients had a rib fracture with 48 patients identified as having an FRF. Median age was 50 years. Thirty-seven (77%) were male. The most common mechanism of FRF was motor vehicle/motorbike accidents (71%). Fifty percent of patients with an observed FRF had the highest global ISS of very severe, with 13% severe, 22% moderate and 15% mild. No patients died from their injuries. Of those with an FRF, 79% experienced fractures other than ribs, 75% had other rib fractures and 52% had chest injuries.A larger than expected proportion of FRFs were not associated with severe trauma scores or high mortality. These findings suggest that patients with an FRF may have a greater chance of surviving their traumatic FRF than previously reported. Clinicians should be aware of the potential for severity and other associated injuries, such as chest wall fractures and thoracic injuries, when treating a patient with a fracture of their first rib.
TIBIAL PLATEAU FRACTURE CHARACTERISTICS: RELIABILITY AND DIAGNOSTIC ACCURACY OF 3D-PRINTED MODELS
Authors: van der Gaast N. , Huitema J.M. , Brouwers L. , Edwards M.J.R. , Hermans E. , Doornberg J.N. , Jaarsma R.L. 
Published: February 2023

Classification systems for tibial plateau fractures suffer from poor interobserver agreement, and their value in preoperative assessment to guide surgical fixation strategies is limited. For tibial plateau fractures four major characteristics are identified: lateral split fragment, posteromedial fragment, anterior tubercle fragment, and central zone of comminution. These fracture characteristics support preoperative assessment of fractures and guide surgical decision-making as each specific component requires a respective fixation strategy. We aimed to evaluate the additional value of 3D-printed models for the identification of tibial plateau fracture characteristics in terms of the interobserver agreement on different fracture characteristics.Preoperative images of 40 patients were randomly selected. Nine trauma surgeons, eight senior and eight junior registrars indicated the presence or absence of four fracture characteristics with and without 3D-printed models. The Fleiss kappa was used to determine interobserver agreement for fracture classification and for interpretation, the Landis and Koch criteria were used.3D-printed models lead to a categorical improvement in interobserver agreement for three of four fracture characteristics: lateral split (Kconv = 0.445 versus K3Dprint = 0.620; P < 0.001), anterior tubercle fragment (Kconv = 0.288 versus K3Dprint = 0.449; P < 0.001) and zone of comminution (Kconv = 0.535 versus K3Dprint = 0.652; P < 0.001).The overall interobserver agreement improved for three of four fracture characteristics after the addition of 3D printed models. For two fracture characteristics, lateral split and zone of comminution, a substantial interobserver agreement was achieved.Fracture characteristics seem to be a more reliable way to assess tibial plateau fractures and one should consider including these in the preoperative assessment of tibial plateau fractures compared to the commonly used classification systems.