bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D Printed Orthopaedic External Fixation Devices: A Systematic Review
Authors: O’Connor Hunter A. , Adams Luke W. , MacFadden Lisa N. , Skelley Nathan Wm. 
Published: June 2023

Abstract
Background
External fixators are complex, expensive orthopaedic devices used to stabilize high-energy and complex fractures of the extremities. Although the technology has advanced dramatically over the last several decades, the mechanical goals for fracture stabilization of these devices have remained unchanged. Three-dimensional (3D) printing technology has the potential to advance the practice and access to external fixation devices in orthopaedics. This publication aims to systematically review and synthesize the current literature on 3D printed external fixation devices for managing orthopaedic trauma fractures.

Methods
The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols were followed for this manuscript with minor exceptions. PubMed, Embase, Cochrane Review, Google Scholar, and Scopus online databases were systematically searched. Two independent reviewers screened the search results based on predetermined inclusion and exclusion criteria related to 3D printing and external fixation of fractures.

Results
Nine studies met the inclusion criteria. These included one mechanical testing study, two computational simulation studies, three feasibility studies, and three clinical case studies. Fixator designs and materials varied significantly between authors. Mechanical testing revealed similar strength to traditional metal external fixators. Across all clinical studies, five patients underwent definitive treatment with 3D printed external fixators. They all had satisfactory reduction and healing with no reported complications.

Conclusions
The current literature on this topic is heterogeneous, with highly variable external fixator designs and testing techniques. A small and limited number of studies in the scientific literature have analyzed the use of 3D printing in this area of orthopaedic surgery. 3D printed external fixation design advancements have yielded promising results in several small clinical case studies. However, additional studies on a larger scale with standardized testing and reporting techniques are needed.
A systematic review of the print media representation of ketamine treatments for psychiatric disorders
Authors: Thornton Nicollette L. R. , Kawalsky Jason , Milton Alyssa , Klinner Christiane , Schokman Aaron , Stratton Elizabeth , Loo Colleen K. , Glozier Nick 
Published: June 2023

BackgroundPublic and patient expectations of treatment influence health behaviours and decision-making.AimsWe aimed to understand how the media has portrayed the therapeutic use of ketamine in psychiatry.MethodWe systematically searched electronic databases for print and online news articles about ketamine for psychiatric disorders. The top ten UK, USA, Canadian and Australian newspapers by circulation and any trade and consumer magazines indexed in the databases were searched from 2015 to 2020. Article content was quantitatively coded with a framework encompassing treatment indication, descriptions of prior use, references to research, benefits and harms, treatment access and process, patient and professional testimony, tone and factual basis.ResultsWe found 119 articles, peaking in March 2019 when the United States Food and Drug Administration approved esketamine. Ketamine treatment was portrayed in an extremely positive light (n= 82, 68.9%), with significant contributions of positive testimony from key opinion leaders (e.g. clinicians). Positive research results and ketamine's rapid antidepressant effect (n= 87, 73.1%) were frequently emphasised, with little reference to longer-term safety and efficacy. Side-effects were frequently reported (n= 96, 80.7%), predominantly ketamine's acute psychotomimetic effects and the potential for addiction and misuse, and rarely cardiovascular and bladder effects. Not infrequently, key opinion leaders were quoted as being overly optimistic compared with the existing evidence base.ConclusionsInformation pertinent to patient help-seeking and treatment expectations is being communicated through the media and supported by key opinion leaders, although some quotes go well beyond the evidence base. Clinicians should be aware of this and may need to address their patients’ beliefs directly.
The impact of cause of mismatch repair deficiency and other molecular markers on clinical outcomes with the use of durvalumab in advanced endometrial cancer in the phase 2 PHAEDRA trial (ANZGOG1601).
Authors: Buchanan Daniel D. , Mahmood Khalid , Georgeson Peter , Walker Romy , Robledo Kristy , Cummins Michelle M. , Spurdle Amanda B. , Smith Deborah S , Joo Eric , Clendenning Mark , Como Julia , Preston Susan , Yip Sonia , Andrews John , Kok Peey Sei , Lee Yeh Chen , Stockler Martin R. , Mileshkin Linda R. , Antill Yoland Catherine ,   Australia New Zealand Gynaeocological Oncology Group (ANZGOG)
Published: June 2023

5604 Background: In the single arm phase 2 PHAEDRA trial, MMR deficiency (dMMR) was predictive of response to durvalumab (1500mg IV Q4W), with an objective tumor response rate (OTR; defined by iRECIST) of 47% in dMMR compared with 3% in MMR-proficient (pMMR) advanced endometrial cancer (AEC). This substudy of the PHAEDRA trial investigates MMR molecular subtypes and other genomic tumor features and their correlation with treatment outcomes. Methods: Testing was performed to determine molecular subtypes of dMMR, including germline pathogenic variants in DNA MMR genes (Lynch syndrome), somatic biallelic MMR gene inactivation through somatic mutation and somatic hypermethylation of the MLH1 gene promoter. DNA from formalin-fixed paraffin-embedded tumor tissue and matched peripheral blood was available from 41/71 (25 dMMR, 16 pMMR) participants for testing on a custom capture-based 298-gene targeted panel (2.005Mb) including the MMR genes and key somatic AEC driver genes. The derived tumor genomic features included microsatellite instability (MSI), tumor mutational burden (TMB), COSMIC v.3.2 tumor mutational signatures and insertion/deletion (Indel) somatic mutation count. Results: Of the 71 patients recruited, 35 were dMMR and 36 were pMMR. Median follow-up was 44 vs 52 months in dMMR vs pMMR participants, respectively. The dMMR molecular subtypes were 4 (11.4%) Lynch syndrome, 4 (11.4%) somatic MMR mutation, 25 (71.4%) MLH1 methylated and 2 (5.7%) dMMR-uncategorised. The OTR rate was 100% (4/4; 95%CI 40-100%) for Lynch, 75% (3/4; 95%CI 22-99%) for somatic MMR mutations and 40% (10/25; 95%CI 22-61%) for MLH1 methylated groups. The median TMB (assessed in 41/71) was higher in those with a confirmed radiological response (37, IQR:26-50) vs non-responders (16, IQR:9-25; p < 0.001). Within the MLH1 methylated group, TMB was also higher in responders vs non-responders (40 v 21; p = 0.03). Somatic mutations in KRAS, PTEN, PIK3CA, ARID1A and TP53 were not associated with OTR rate. Conclusions: dMMR- MLH1 methylated AEC demonstrated greater heterogeneity in OTR to single agent durvalumab than the dMMR-Lynch and dMMR-somatic MMR mutation molecular subtypes. Higher TMB was seen in responders, and specifically within dMMR- MLH1 methylated responders, compared to non-responders. Clinical trial information: ANZGOG1601.
Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): A randomized clinical trial.
Authors: Ebrahimi Hedyeh , Meza Luis A. , Lee Keehoon , Malhotra Jasnoor , Alcantara Marice , Zengin Zeynep Busra , Dizman Nazli , Govindarajan Ameish , Hsu Joann , Llamas-Quitiquit Marian , Chawla Neal Shiv , Castro Daniela V. , Mercier Benjamin D. , Liu Sandy , Chehrazi-Raffle Alex , Dorff Tanya B. , Frankel Paul Henry , Li Xiaochen , Pal Sumanta Kumar , Tripathi Abhishek 
Published: June 2023

LBA104 Background: We have previously demonstrated that the live bacterial product CBM588 may augment clinical outcomes in pts with mRCC receiving 1st-line (1L) therapy with dual immune checkpoint inhibitors (ICIs; Dizman et al Nature Medicine 2022). As tyrosine kinase inhibitors (TKIs) in combination with ICIs also represent a 1L standard of care in mRCC, we sought to determine if CBM588 would augment clinical outcome with the TKI cabozantinib (cabo) with nivo. Methods: Eligible pts were ≥18 yrs old (Karnofsky performance status ≥70%) with histologically verified (clear-cell, papillary or sarcomatoid component) mRCC and no prior systemic therapy for metastatic disease. Patients were randomized 1:2 to receive either cabo/nivo at the standard dose/schedule (40mg PO QD and 480mg IV monthly, respectively) alone or with CBM588 dosed at 80mg PO BID. The primary endpoint was the relative abundance of Bifidobacterium spp. in stool specimens at baseline and after 12 weeks of treatment. Secondary endpoints included assessment of response rate, overall survival, progression-free survival (PFS), systemic immunomodulation, and toxicity. A two-group t-test with a one-sided type I error of 0.05 was used to assess the study's primary endpoint, hypothesizing an increase in Bifidobacterium spp. with CBM588 therapy. Results: A total of 30 (20:10 M:F) pts were recruited; median age was 65 (36-84) and 5 pts (17%) had sarcomatoid features and 2 pts (7%) had predominant papillary histology. 12 (40%), 12 (40%) and 6 pts (20%) had good, intermediate and poor risk, respectively. Metagenomic sequencing of paired stool specimens showed a significant decrease in diversity from baseline to week 12 in patients receiving cabo/nivo (P=0.02); no significant difference was observed in those treated with cabo/nivo+CBM588. No significant change in Bifidobacterium spp. was observed. RR was 63% in pts receiving cabo/nivo+CBM588 vs 33% in pts receiving cabo/nivo alone. Median PFS was not reached in pts receiving CBM588 vs 5.8 mos in pts receiving cabo/nivo along (P=0.03). Grade 3/4 toxicities were observed in 44% and 42% of patients on control and experimental arms, respectively. Conclusions: In the second prospective trial assessing the addition of CBM588 to ICI-based therapy in mRCC, a consistent result with improved PFS and RR was observed. Further translational efforts are underway to characterize the mechanism through which CBM588 augments clinical activity. Clinical trial information: NCT05122546 .
First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma.
Authors: Dhakal Binod , Yong Kwee , Harrison Simon J. , Mateos Maria-Victoria , Moreau Philippe , van de Donk Niels W.C.J. , Sidana Surbhi , Popat Rakesh , Lendvai Nikoletta , Lonardi Carolina , Slaughter Ana , Schecter Jordan Mark , Li Katherine , Zudaire Enrique , Chen Ying , Gilbert Jane , Bubuteishvili-Pacaud Lida , Patel Nitin , San-Miguel Jesús , Einsele Hermann 
Published: June 2023

LBA106 Background: CARTITUDE-4 is a global, phase 3, randomized, controlled trial (NCT04181827) of ciltacabtagene autoleucel (cilta-cel), a dual-binding, BCMA-targeting CAR-T cell therapy, vs standard of care (SOC; pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]) in lenalidomide (len)-refractory patients (pts). Methods: Eligible pts had 1–3 prior lines of therapy (LOT), including PI and IMiD, and were len-refractory. After apheresis, pts randomized to cilta-cel received PVd or DPd (physician’s choice) bridging therapy, then 1 cilta-cel infusion 5–7 days after lymphodepletion. In the SOC arm, pts received PVd or DPd until progression. Primary endpoint was progression-free survival (PFS) in the intent-to-treat (randomized) population. Results: 419 pts were randomized (cilta-cel, n=208; SOC, n=211 [PVd, n=28; DPd, n=183]). 176 pts received cilta-cel as study treatment (tx), 20 more received it after PD on bridging therapy, and 208 received SOC. There were no manufacturing failures. Baseline characteristics were balanced (cilta-cel vs SOC: 59% vs 63% cytogenetic high risk [including gain/amp 1q]; 50% vs 46% PI refractory; 24% vs 22% anti-CD38 refractory; 33% vs 32% had 1 prior LOT). Median dose was 0.71×106 CAR+ viable T cells/kg. At Nov 1, 2022, data cut-off, median follow-up was 16 mo (range, 0.1–27). Primary endpoint was met; cilta-cel reduced risk of progression/death by 74% (HR=0.26; P<0.0001). Cilta-cel vs SOC significantly improved ORR, rate of ≥CR, and overall MRD negativity rate (Table), with a positive trend in OS (HR, 0.78; 95% CI, 0.5–1.2). 97% and 94% of pts treated in the cilta-cel or SOC arms, respectively, had grade (gr) 3/4 AEs, including infections (27% vs 25%) and cytopenias (94% vs 86%). In the cilta-cel and SOC arms, respectively, 39 and 46 pts died (14 and 30 due to PD). In pts who received cilta-cel as study tx (n=176), 76% had CRS (1% gr 3; no gr 4/5) and 5% had ICANS (all gr 1/2). 1 pt had a gr 1 movement/neurocognitive TEAE. Conclusions: A single cilta-cel infusion significantly improved PFS vs SOC in len-refractory pts with 1–3 prior LOT, with a favorable benefit/risk profile across pt populations. The 74% reduction in progression/death and high rates of CR and MRD negativity highlight the potential for cilta-cel to become a key therapy for pts with MM after first relapse. Clinical trial information: NCT04181827 . [Table: see text]
Oral paclitaxel, carboplatin, and dostarlimab (OPE/Cb/D) without and with trastuzumab in early-stage, high-risk breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL.
Authors: Yeung Kay T , Kalinsky Kevin , Yau Christina , Chien Amy Jo , Boughey Judy Caroline , Stringer-Reasor Erica Michelle , Falkson Carla Isadora , Albain Kathy S. , Mayer Ingrid A. , Trivedi Meghna S. , Nanda Rita , Douglas Emily H. , Omene Coral Oghenerukevwe , Rugo Hope S. , Isaacs Claudine , Parker Beverly , DeMichele Angela , Yee Douglas , Esserman Laura ,   I-SPY Investigators
Published: June 2023

LBA520 Background: I-SPY 2 is a multicenter trial using response-adaptive randomization within biomarker subtypes including MammaPrint (MP) risk to evaluate novel neoadjuvant agents in high-risk breast cancer. Oral paclitaxel and encequidar (OPE) is an oral combination of paclitaxel (P) with a p-glycoprotein pump inhibitor, encequidar, to enhance gastrointestinal (GI) absorption. Dostarlimab (D) is an anti-PD-1 monoclonal antibody. Methods: Women with tumors ≥ 2.5cm and MP high-risk cancers were screened and treated starting Oct 5, 2020. Treatment included Oral Paclitaxel 205mg/m2 and encequidar 12.9 mg on days 1-3, Carboplatin (Cb) AUC 1.5 on day 1 weekly x 12, and Dostarlimab (D) 500 mg every 3 weeks x 4, followed by doxorubicin/ cyclophosphamide (AC) every 2-3 weeks x 4. The control arm was IV P weekly x 12 followed by AC every 2-3 weeks x 4. For patients with HER2+ disease, weekly Trastuzumab (T) was administered during the first 12 weeks. The arm was eligible for graduation [> 85% chance of success in a 300-person phase 3 neoadjuvant trial with a pathologic complete response (pCR) endpoint] in 10 predefined signatures. Results: 106 patients (44 HR+HER2-, 56 HR-HER2- (TN), 6 HER2+) received OPE/Cb/D ± T. The control arm included 388 historical controls (201 HR+HER2-, 156 TN, 31 HER2+). 22 patients (20 HR+, 2 HR-) in OPE/Cb/D were MP1 (MP high) and 84 patients (29 HR+, 55 HR-) were MP2 (MP ultra-high). OPE/Cb/D graduated in the TN signature and accrual was stopped. Conclusions: OPE/Cb/D graduated in the TN signature with a higher predicted pCR rate compared to control. OPE and D have been, individually, shown to have efficacy in other settings. The lower-than-expected pCR rate and lower irAEs with triplet therapy (taxane, platinum, immune checkpoint inhibitor [ICI]) in TN compared to prior IV chemo + ICI arms on I-SPY 2 suggests a possible interference of OPE with ICI. Changes in gut microbiome is being investigated as an explanation. Clinical trial information: NCT01042379 . [Table: see text]
Phase III MIRASOL (GOG 3045/ENGOT-ov55) study: Initial report of mirvetuximab soravtansine vs. investigator's choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression.
Authors: Moore Kathleen N. , Angelergues Antoine , Konecny Gottfried E. , Banerjee Susana N. , Pignata Sandro , Colombo Nicoletta , Moroney John William , Cosgrove Casey , Lee Jung-Yun , Roszak Andrzej , Breuer Shani , Tromp Jacqueline Maria , Bello-Roufai Diana , Gilbert Lucy , Miller Rowan , Myers Tashanna K. N. , Wang Yuemei , Berkenblit Anna , Lorusso Domenica , Van Gorp Toon 
Published: June 2023

LBA5507 Background: Mirvetuximab soravtansine (MIRV), an antibody drug conjugate targeting FRα, demonstrated clinically meaningful antitumor activity in a single arm trial reported previously (Matulonis, JCO 2023). MIRASOL is a randomized phase 3 trial to confirm the efficacy of MIRV vs standard-of-care chemotherapy in patients (pts) with PROC. Methods: 453 PROC pts with high FRα expression (Roche FOLR1 Assay) with 1-3 priors were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or IC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. The primary efficacy endpoint was progression-free survival (PFS) by investigator (INV) with key secondary endpoints ORR, overall survival (OS), and patient-reported outcomes in hierarchical order; other endpoints included safety and tolerability. Blinded independent central review (BICR) for PFS and ORR were sensitivity analyses. Results: With a data cutoff of March 6, 2023, 227 pts were randomized to the MIRV arm; 226 to the IC arm. Median follow-up was 13.1 months. Baseline characteristics were well balanced across arms; 14% of pts had one, 39% two, and 47% three prior lines of therapy; 62% received prior bev; and 55% received prior PARPi therapy. The study met its primary and key secondary endpoints with statistically significant results in PFS (INV), ORR (INV), and OS (Table). In the bev-pretreated subset (n=281), PFS HR was 0.64 (0.492, 0.842) and OS HR was 0.74 (0.535, 1.036); in the bev-naïve subset (n=172), PFS HR was 0.66 (0.459, 0.942) and OS HR was 0.51 (0.306, 0.860). The adverse event (AE) profile of MIRV was consistent with prior reports: predominantly low-grade ocular (MIRV vs IC all grade 56% vs 9%; grade 3+ 14% vs 0%) and gastrointestinal events (MIRV vs IC all grade 70% vs 66%; grade 3+ 13% vs 15%). Compared with IC, MIRV was associated with lower rates of grade 3+ treatment-emergent AEs (42% vs 54%), serious AEs (24% vs 33%), and discontinuations due to TEAEs (9% vs 16%). Fourteen percent of pts on the MIRV arm remained on study drug vs 3% on the IC arm. Conclusion: MIRV is the first treatment to demonstrate a PFS and OS benefit in PROC compared to IC. The efficacy data, along with the well-characterized safety profile, position MIRV as a new, standard of care for pts with FRα positive PROC. Clinical trial information: NCT04209855 .[Table: see text]
Predicting unresolved scales interactions with 3D neural networks in homogeneous isotropic turbulence
Authors: Saura N. , Gomez T. 
Published: June 2023

Abstract
Interactions between the different scales of motion featured by any turbulent flow are currently mathematically and numerically intractable. Instead, numerical reduced models, such as Large Eddy Simulations (LES), have been proposed: large-scale motions are resolved using the large eddy equations whereas small-scale influence is modeled through the subgrid stress tensor and injected into the large-scale dynamics. In this paper, we develop the learning of this tensor from the raw 3D filtered velocity field diced into sub-cubes whose length is turbulence-induced. We used the U-net convolutional neural network architecture. The performance is assessed using component-wise correlations, PDF and contours comparisons. We extended our a priori analyses to monitor the impacts of such predictions on momentum and kinetic energy evolution. Our model is shown to perform well considering velocity fields extracted from 150% more turbulent simulations.
“Scotch! Scotch! Scotch!”: The Inoperative Domestic Scene in Chantal Akerman's Saute ma ville
Authors: Rowe-Stefanik Eleanor 
Published: June 2023

Abstract
This article reads Chantal Akerman's short film Saute ma ville (Blow Up My Town, Belgium, 1968) with and against texts by Giorgio Agamben, Gilles Deleuze, and Herman Melville. Rather than being merely a precursor to Akerman's later genre-defining efforts in recording female domestic life, I propose that Saute ma ville displays the potentiality for domestic labor itself to be a destituent practice, rather than an expected component of reproductive, conventionally gendered work. The way that Akerman mobilizes the inoperative actions of her protagonist — a “girl without references” — in her “preference not to” perform the supportive labor of the domestic space and in so doing literally “blow up her town” makes this early work interpretable as structurally concerned and politically motivated recit in the mode of her later films, rather than merely narrative-focused histoire. The protagonist of the film, in her Chaplinesque resistance to allow household chores to sustain her home, displays a conceptual paradigm in which those still separated from politics and from the space of the polis may yet act politically. Reading the film with Melville's Bartleby the Scrivener and Deleuze's and Agamben's responses to that text puts pressure on the limits of Agamben's thought on inoperativity and reinscribes the importance of Akerman's deeply affective cinematography within an anti-capitalist feminist critique.
Her Body, Her Choice: Tough Girl Affect, Trump Support, and the 2020 Pandemic
Authors: Stümer Jenny 
Published: June 2023

Abstract
When anti-lockdown protests erupted in the United States during the 2020 onset of the COVID-19 pandemic, many right-wing women crudely appropriated the feminist slogan “my body, my choice” in defiance of liberal fears and in support of Donald Trump. Looking at the widely shared image of a young woman holding a sign with the phrase at a rally in Texas, I discuss the communal charge of what I call tough girl affect—a politically saturated vibe, touting a notably youthful, right-wing femininity that is deliberately feisty, fun, and provocative, yet compliant with the hetero-patriarchal agenda of Trump’s neoliberal macho politics. I am interested in the way body and choice evoke white femininity as affective strategy, negotiating a public feeling of privileged belonging to the nation. The article works through the tenets of body, border, and nation as central to this investment, suggesting that the tough girl image mobilizes femininity to affectively strengthen conservatism, whiteness, and homeland in the face of the pandemic. Staging a fantasy of impunity, the tough girl intimates the invincible conservative body in opposition to the porous emotionality of feeble liberals. At the same time, the spectacle of white femininity necessarily fuels national fears of permeability and hence charges negative (even fatal) attachments to fantasmatic sovereignty. While mobilizing vulnerability to energize femininity, whiteness, and borders, the image ultimately exposes the compromised bargains of living and dying in (Trump’s) America.