bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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.
Voice and Silence in Assia Djebar and Adania Shibli
Authors: Silmi Amirah
Published: June 2023

This essay considers the works of two Arab writers, Assia Djebar and Adania Shibli, to examine how silences in their texts are signs of both oppression and of resistance and rebellion. It seeks to show how the silences as well as the cries and incomprehensible voices of the colonized defy colonial and hegemonic narratives by resisting incorporation into the order of the intelligible and recognizable. Both writers believe in the power of words, but their words, liberated from the function of signification, release silences as they release the voices of the colonized in their multiplicity. Djebar's texts present no binary opposition between silence and voice; in the continuous search for the voices of colonized women, voice and silence are inextricably intertwined. In Shibli's Minor Detail, as in many of Djebar's texts, the search for voices takes the form of a journey backward, but the voices of the colonized are not retrieved, and we are left with only their silence. Moreover, whatever audible voices there are in Shibli's text become markers of silence; it is thus silence that speaks in Shibli's text. By virtue of their very lack of discursive power, the silences and voices released in these writers' works retain the freedom that comes with transgression and remind us of the flight that writing can be.
THE USE OF BIODIESEL TO REDUCE CO2 EMISSIONS CAUSED BY THE URBAN BUS FLEET OF RIO DE JANEIRO
Authors: Soares Murta Aurelio Lamare
Published: June 2023

For several years, the use of oil to move vehicles, transport people, generate energy and other activities necessary for social life, has made the world very dependent on this input. Among the alternative fuels studied, we have the biodiesel, a fuel obtained through the transesterification process of vegetable oils or animal fats, which has become a potential substitute for petroleum diesel. Among the advantages of using this fuel, the following stand out: being renewable, reducing the country’s dependence on oil, and having lower rates of greenhouse gas emissions than petro diesel. Among those gases stands out the CO2, which contributes to the global warming and will be the target of this study. Based on the calculations made taking into account the consumption of petro diesel in Rio de Janeiro, it is intended to quantify the emissions from its use up to 2030 in the fleet of urban buses of the city of Rio de Janeiro and, in parallel, calculate the potential to reduce emissions with the use of biodiesel in the percentages established by the Brazilian Government in the same period.
CORREDORES MULTIMODAIS PARA EXPORTAÇÃO DE GRÃOS NO MATO GROSSO: UMA ANÁLISE DE CONCORRÊNCIA
Authors: Péra Thiago Guilherme , Caixeta-Filho José Vicente
Published: June 2023

O Mato Grosso, principal estado produtor de grãos, apresenta um déficit logístico que reduz a sua competitividade. A expansão do sistema ferroviário na região é fundamental para redução dos seus custos logísticos e fortalecimento da competitividade. O objetivo desta pesquisa foi realizar uma análise de demanda dos corredores multimodais de exportação de grãos, envolvendo o corredor atual de Rondonópolis para Santos, bem como, analisar a demanda de três projetos futuros em discussão, envolvendo: a criação da Ferrogrão, a expansão da ferrovia Malha Norte e a construção da Ferrovia Paraense. O principal resultou ilustrou que os corredores de Rondonópolis, Ferrogrão e Malha Norte são importantes para redução dos custos, entretanto, é fundamental a redução dos preços dos fretes ferroviários para expandir a demanda nos corredores.
The cloud paradigm
Authors: Ρουγγέρης Κωνσταντίνος
Published: June 2023

Το Cloud Computing («νεφοϋπολογιστική» ή «υπολογιστικό νέφος») έχει μεταμορφώσει τον τρόπο με τον οποίο οργανισμοί καταναλώνουν υπηρεσίες τεχνολογίας όπως κανένα άλλο πρόσφατο πρότυπο. Αντανακλά ένα ευρύ, συνεχώς εξελισσόμενο οικοσύστημα υπηρεσιών και μεθοδολογιών που έχουν δημιουργήσει νέα καταναλωτικά και επιχειρηματικά μοντέλα, με αντίκτυπο τόσο στον ιδιωτικό όσο και στον δημόσιο τομέα. Την τελευταία μιάμιση δεκαετία, ο κλάδος των υπηρεσιών πληροφορικής και η ακαδημαϊκή κοινότητα στοχεύουν να συλλάβουν την πρωτοποριακή ανέλιξη του cloud, προσεγγίζοντάς το τόσο από μηχανολογικό, όσο και από επιχειρηματικό πρίσμα.Ωστόσο, η ευρύτητα χρήσης και η διασημότητα που απέκτησε ο όρος, το πλήθος των αλληλένδετων τεχνολογικών εννοιών που εμπλέκονται, τα διαφορετικά μοντέλα ανάπτυξης και οι πολλές περιπτώσεις χρήσης, έχουν αποτελέσει προκλήσεις προς την καθιέρωση μιας καθολικής αντίληψης για το cloud και σε ορισμένες περιπτώσεις τη συνεκτική και αποτελεσματική περιγραφή του.Νωρίς και πριν ακόμη επινοηθεί ο όρος “cloud”, η ακαδημαϊκή κοινότητα έκανε σταδιακά βήματα προς τον καλύτερο προσδιορισμό και τη μέτρηση του αντίκτυπου σε μια ποικιλία περιπτώσεων χρήσης. Ταυτόχρονα, κυβερνητικά όργανα όπως η Ευρωπαϊκή Ένωση έχουν υποστηρίξει την υιοθέτησή του σε εθνικό και περιφερειακό επίπεδο, αναγνωρίζοντας την ανάγκη τυποποίησης προκειμένου αυτή να επιταχυνθεί.Αυτή η διδακτορική διατριβή εξετάζει την υιοθέτηση του cloud computing χρησιμοποιώντας πρωτογενή δεδομένα με βάση τη διαθέσιμη βιβλιογραφία, σε δύο διαφορετικά σενάρια: στον ιδιωτικό τομέα από επιχειρήσεις και οργανισμούς και στον δημόσιο από τις εθνικές κυβερνήσεις. Η πρώτη περίπτωση χρήσης που εξετάζουμε εστιάζει στην υιοθέτηση του cloud computing από επιχειρήσεις. Αξιοποιούμε πρωτογενή δεδομένα από τους υπεύθυνους λήψης αποφάσεων ελληνικών επιχειρήσεων και οργανισμών, για να ελέγξουμε και να ποσοτικοποιήσουμε τους - ήδη διατυπωμένους από την βιβλιογραφία - παράγοντες κινήτρων υιοθέτησης cloud, και να διερευνήσουμε επιπλέον ευρήματα, όπως η κατάταξή τους ή άλλες στατιστικά σημαντικές συσχετίσεις μεταξύ τους.Στη δεύτερη περίπτωση χρήσης, εστιάζουμε στη χρήση του cloud από τις κυβερνήσεις ως μέρος εθνικής στρατηγικής, χρησιμοποιώντας πρωτογενή δεδομένα από αξιωματούχους των κρατών μελών της Ευρωπαϊκής Ένωσης, σε μια προσπάθεια να επεκτείνουμε τον υπάρχοντα ορισμό του «GovCloud» και να προσφέρουμε μια νέα χρηστική ταξινομία αποτελούμενη από τρία μοντέλα.
Major depression disorder - etiology and treatment
Authors: Czuchryta Paulina , Babiak Rafał , Bajak Karolina , Domańska Anastazja , Gawęda Agnieszka , Grabek Agata , Rutkowska Julia , Rzęsa-Tokarczyk Żaneta , Skorek Klaudia , Urbańczyk Agnieszka
Published: June 2023

Introduction and purpose: The problem of major depression disorder (MDD) affects more and more people. In a few years, it may become the most common disease after cardiovascular diseases and cancer. MDD are manifested by a depressed mood, decreased energy, loss of interest and the ability to enjoy life, as well as a number of other additional symptoms. Untreated MDD can lead to disability. This entails not only consequences for the sick person but also increased social costs. That is why it is so important to know the causes of its formation and to look for new therapeutic methods.

State of knowledge: The development of MDD is influenced by genetic factors, inflammatory factors and hormonal disorders, changes in the structure of the brain, disorders in neurotransmission. The microbiome-gut-brain axis affects mood regulation and neurotransmission in the brain. Bacteria such as Escherichia, Shigella, Enterococcus, Streptococccus, Alistipes, Parabacterioides, Veillonella have been identified as having a potential negative effect on the development of MDD and response to treatment. The use of probiotics containing Lactobacillus helveticus R0052, Bifidobacterium longum and Clostridium butyricum MIYAIRI 588 may help reduce the symptoms of MDD. In recent years, the US Food and Drug Administration (FDA) has approved the intranasal preparation of esketamine for the treatment of treatment-resistant depression and major depressive disorder with severe suicidal thoughts. Unlike other antidepressants, it has a quick effect on reducing symptoms.

Summary: Due to the global problem of MDD, further research is needed to better understand the mechanisms of its formation. Particular attention should be paid to the influence of microbiota.
The role of B lymphocytes in selected rheumatological and neurological diseases
Authors: Zarańska Julia , Aab Arkadiusz , Miejska-Kamińska Marta , Kamiński Filip , Liszka Adriana
Published: June 2023

Introduction: B lymphocytes are responsible for humoral immune response. They play a crucial role in the development of the immune response and are essential in preventing infections as well as autoimmune and neoplastic diseases. They also constitute an important therapeutic target and are used in genetic and immunological therapies. In some cases, B cells can contribute to the pathogenesis of various diseases.
Aim of study: The aim of this study is to summarize the current knowledge on the diverse role of B lymphocytes in selected rheumatic and neurological diseases using available scientific literature.
Materials and Methods: This  review was conducted using  Pubmed and Google Scholar databases from 2009-2023. The research strategy was based on the following terms: B lymphocytes, monoclonal antibodies, myasthenia gravis, multiple sclerosis, systemic lupus erythematosus, systemic sclerosis, central nervous system damage, optic neuritis, Devic's syndrome.
Conclusion: B lymphocytes play a significant role in the pathogenesis of many rheumatic and neurological diseases, therefore they represent a target for modern therapies. Their role and potential use are complex and differ depending on the specific disease entity. Further research will allow for the development of new targeted therapies, giving hope for improving the effectiveness of patient treatment.
When the Clock Strikes: A Multimethod Investigation of On-the-Hour Effects in Online Learning
Authors: Huang Ni , Wang Lingli , Hong Yili , Lin Lihui , Guo Xunhua , Chen Guoqing
Published: June 2023

Online learners often experience a lack of sustained motivation given the self-paced nature of online learning, resulting in inefficiency and a high dropout rate. It is important to explore options that help users optimize their learning behavior and improve their learning performance. Using a multimethod approach, we show that (a) starting learning sessions at on-the-hour time points activates users’ implemental mindset, which supports them in building greater learning persistence and achieving better learning performance, and (b) social presence significantly attenuates the effects of on-the-hour time points in online learning. Based on our findings, we suggest that both learners and instructors on online learning platforms can leverage common temporal cues, such as on-the-hour time points, to schedule learning activities in order to motivate online learners, enhance their learning persistence, and improve their learning performance. Additionally, online learning platforms can also adopt designs that facilitate virtual connections among geographically separated users to enhance their learning productivity.
Tummy time
Authors: Rodgers Anne
Published: June 2023

Anne Rodgers shares an introduction to tummy time and provides some ideas you could share with your families and how to do this at home and why.
Statistical Study of the Patient of Department of Acupuncture and Moxibustion at OO Korean Medicine Hospital in Daejeon - from September, 2019 to September, 2022 -
Authors: Kim So Jeong , Jang Hyun Jin , Kim Min Ju , Choi Hyeon Kyu , Park Pil Je , Kang Yeon Soo , Kim Hong Kyoung , Jeong Jeong Kyo , Jeon Ju Hyun , Kim Young Il
Published: June 2023

Objectives: This study is designed to statistically analyze the features of patients who visited to Department of Acupuncture and Moxibustion at OO Korean Medicine Hospital for 3 years.Methods: This study retrospectively analyzed the medical records of patients at Department of Acupuncture and Moxibustion at OO Korean Medicine Hospital using IBM SPSS ver. 27.0 for Windows.Results: 1. In the analysis of the total number of patients, those in their 30s accounted for the highest percentage, male patients had a higher rate. 2. In the analysis of KCD-8 code, spinal stenosis and fractures in areas other than the spine were the most common in the 70s and older, and cervical sprains were the most common in other. 3. In the analysis of the number of hospitalizations, patients classified as illness or higher age had more re-hospitalization than patients classified as injury or lower age in first-time care. 4. In the analysis of hospitalization duration, patients classified as illness, female or higher age had longer hospitalization duration than patients classified as accident, male or lower age in first-time care.Conclusion: We expect that the results of this study would be used as reference materials for analyzing medical consumption condition of Department of Acupuncture and Moxibustion.
From Friction, Heat: Kroetsch, Spanos, and boundary 2
Authors: Eso David
Published: June 2023

Canadian poet, novelist, and critic Robert Kroetsch co-founded the journal boundary 2 with American critic and philosopher William Spanos. The editors' relationship, marked by sympathy and difference, informed this endur-ng publication's early history.
Orbital angular momentum mode fiber force sensing technology based on intensity interrogation
Authors: Lyu Shuhan , Guan Yaojun , Shi Xinghua
Published: June 2023

Micromanipulation and biological, materials science, and medical applications often require controlling or measuring the forces exerted on small objects. Based on the high linearity and sensitivity of OAM beams in the sensing field, this article proposes for the first time to apply OAM beams to force sensing. In this paper, a fiber optic force sensing technology based on the intensity distribution change of orbital angular momentum (OAM) mode is proposed and realized. This technique detects the magnitude of the external force applied to the fiber by exciting the OAM mode with a topological charge 3, thereby tracking changes in light intensity caused by mode coupling. Applying this technique to force measurement, we have experimentally verified that when the sensor is subjected to a force in the range of 0mN to 10mN, the change in speckle light intensity at the sensor output has a good linear relationship with the force. Meanwhile, theoretical analysis and experimental results indicate that compared with previous force sensing methods, this sensing technology has a simple structure, is easy to implement, has good stability, and has practical application potential.
Nonlinear pulse compression of a 200 mJ and 1 kW ultrafast thin-disk amplifier
Authors: Pfaff Yanik , Barbiero Gaia , Rampp Michael , Klingebiel Sandro , Brons Jonathan , Teisset Catherine Y. , Wang Haochuan , Jung Robert , Jaksic Jasna , Woldegeorgis Abel H. , Trunk Maximilian , Maier Andreas R. , Saraceno Clara J. , Metzger Thomas
Published: June 2023

We present a high-energy laser source consisting of an ultrafast thin-disk amplifier followed by a nonlinear compression stage. At a repetition rate of 5 kHz, the drive laser provides a pulse energy of up to 200 mJ with a pulse duration below 500 fs. Nonlinear broadening is implemented inside a Herriott-type multipass cell purged with noble gas, allowing us to operate under different seeding conditions. Firstly, the nonlinear broadening of 64 mJ pulses is demonstrated in an argon-filled cell, showing a compressibility down to 32 fs. Finally, we employ helium as a nonlinear medium to increase the energy up to 200 mJ while maintaining compressibility below 50 fs. Such high-energy pulses with sub-50 fs duration hold great promise as drivers of secondary sources.
Hebbian learning with elasticity explains how the spontaneous motor tempo affects music performance synchronization
Authors: Roman Iran R. , Roman Adrian S. , Kim Ji Chul , Large Edward W.
Published: June 2023

A musician’s spontaneous rate of movement, called spontaneous motor tempo (SMT), can be measured while spontaneously playing a simple melody. Data shows that the SMT influences the musician’s tempo and synchronization. In this study we present a model that captures these phenomena. We review the results from three previously-published studies: solo musical performance with a pacing metronome tempo that is different from the SMT, solo musical performance without a metronome at a tempo that is faster or slower than the SMT, and duet musical performance between musicians with matching or mismatching SMTs. These studies showed, respectively, that the asynchrony between the pacing metronome and the musician’s tempo grew as a function of the difference between the metronome tempo and the musician’s SMT, musicians drifted away from the initial tempo toward the SMT, and the absolute asynchronies were smaller if musicians had matching SMTs. We hypothesize that the SMT constantly acts as a pulling force affecting musical actions at a tempo different from a musician’s SMT. To test our hypothesis, we developed a model consisting of a non-linear oscillator with Hebbian tempo learning and a pulling force to the model’s spontaneous frequency. While the model’s spontaneous frequency emulates the SMT, elastic Hebbian learning allows for frequency learning to match a stimulus’ frequency. To test our hypothesis, we first fit model parameters to match the data in the first of the three studies and asked whether this same model would explain the data the remaining two studies without further tuning. Results showed that the model’s dynamics allowed it to explain all three experiments with the same set of parameters. Our theory offers a dynamical-systems explanation of how an individual’s SMT affects synchronization in realistic music performance settings, and the model also enables predictions about performance settings not yet tested.
Does partisanship shape public support for suspending U.S. federal gas tax? A survey experiment
Authors: Uji Azusa , Song Jaehyun , Dolšak Nives , Prakash Aseem
Published: June 2023

In the wake of Russia’s invasion of Ukraine in February 2022, the national average gasoline price in the U.S. rose sharply. In response, President Biden wanted Congress to temporarily suspend the 18.4 cents per gallon federal gasoline tax. However, critics pointed out that gas tax suspension could: (1) undermine U.S. climate policy goals by encouraging the use of gasoline cars, (2) threaten U.S. national security by providing additional oil revenue to the Russian government for expanding its military capabilities, and (3) undermine the economy by defunding federal highway infrastructure. To systematically test how these critiques influenced public support for gas tax suspension, we administered an online survey experiment in May 2022 to a representative sample of U.S. respondents (N = 1,705). We found that in spite of high inflation during the months when the survey was conducted, in the aggregate, national security and the economy framesreducedpublic support for the gas tax suspension while the climate frame had no such effect. Yet, at the disaggregated level we find important partisan differences. When we interact treatment frames with respondents’ party identification, the national security and the economy frames reduced public support for the gas tax suspension among Republicans only, while the climate frame reduced public support among Democrats only.
Early infant diagnosis testing for HIV in a hard-to-reach fishing community in Uganda
Authors: Ndyanabo Remegio , Nalugya Aisha , Ssekamatte Tonny , Nakafeero Mary , Kisakye Angela , Mukose Aggrey David
Published: June 2023

Background

Infants born to HIV-infected mothers are at a high risk of acquiring the infection. The World Health Organization recommends early diagnosis of HIV-exposed infants (HEIs) through deoxyribonucleic acid polymerase chain reaction (DNA PCR) and rapid HIV testing. Early detection of paediatric HIV is critical for access to antiretroviral therapy (ART) and child survival. However, there is limited evidence of the factors associated with receiving early infant diagnosis (EID) tests of the HIV testing protocol among HEIs in fishing communities in Uganda. This study established the factors associated with receiving EID tests of the HIV testing protocol among HEIs in a hard-to-reach fishing community in Uganda.

Methods

A cross-sectional study was conducted among HEIs in selected healthcare facilities in Buvuma islands, Buvuma district. We obtained secondary data from mother-infant pair files enrolled in the EID program using a data extraction tool. Data were analysed using STATA Version 14. A modified Poisson regression analysis was used to determine the factors associated with not receiving the 1st DNA PCR test among HEIs enrolled in care.

Results

None of the HEIs had received all the EID tests prescribed by the HIV testing protocol within the recommended time frame for the period of January 2014-December 2016. The proportion of infants that had received the 1st and 2nd DNA PCR, and rapid HIV tests was 39.5%, 6.1%, and 81.0% respectively. Being under the care of a single mother (PR = 1.11, 95% CI: 1.01–1.23, p = 0.023) and cessation of breastfeeding (PR = 0.90, 95% CI: 0.83–0.98, p = 0.025) were significantly associated with not receiving the 1st DNA PCR.

Conclusion

Our study revealed that none of the HEIs had received all the EID tests of the HIV diagnosis testing protocol. Receiving the 1st DNA PCR was positively associated with being an infant born to a single mother, and exclusive breastfeeding. Our findings highlight the need for the creation of an enabling environment for mothers and caregivers in order to increase the uptake of early diagnosis services for HEIs. Awareness-raising on the importance of EID should be scaled up in fishing communities. Demographic characteristics such as marital and breastfeeding status should be used as an entry point to increase the proportion of HEIs who receive EID tests.
New species of Kuqaia from the Lower Jurassic of Sweden indicates a possible water flea (Crustacea: Branchiopoda) affinity
Authors: Peng Jungang , Slater Sam M. , McLoughlin Stephen , Vajda Vivi
Published: June 2023

The enigmatic acid-resistant mesofossil genus Kuqaia is emended, a new species (Kuqaia scanicus) is instituted, and three established species are described from the Lower Jurassic (lower Pliensbachian) of the Kävlinge BH-928 core, in southern Sweden. Kuqaia has a distribution across the middle northern latitudes of Pangaea and is restricted to Lower to lower Middle Jurassic strata. Morphological characters support Kuqaia being the ephippia (resting egg/embryo cases) of Cladocera (Crustacea: Branchiopoda), and a probable early stem-group taxon of the Daphnia lineage. The paleoecology of the small planktonic crustaceans indicate purely fresh-water environments, such as lakes or ponds, all occurrences being in continental deposits, and the Kuqaia specimens possibly represent dry-season resting eggs. Chemical analyses of these and similar fossils, and of extant invertebrate eggs and egg cases are recommended to improve resolution of the biological affiliations of such mesofossil groups.
Bayesian versus diagnostic information in physician-patient communication: Effects of direction of statistical information and presentation of visualization
Authors: Brose Sarah Frederike , Binder Karin , Fischer Martin R. , Reincke Martin , Braun Leah T. , Schmidmaier Ralf
Published: June 2023

Background

Communicating well with patients is a competence central to everyday clinical practice, and communicating statistical information, especially in Bayesian reasoning tasks, can be challenging. In Bayesian reasoning tasks, information can be communicated in two different ways (which we calldirections of information): The direction ofBayesian information(e.g., proportion of people tested positive among those with the disease) and the direction ofdiagnostic information(e.g., the proportion of people having the disease among those tested positive). The purpose of this study was to analyze the impact of both the direction of the information presented and whether a visualization (frequency net) is presented with it on patient’s ability to quantify a positive predictive value.

Material and methods

109 participants completed four different medical cases (2⨯2⨯4 design) that were presented in a video; a physician communicated frequencies using different directions of information (Bayesian information vs. diagnostic information). In half of the cases for each direction, participants were given a frequency net. After watching the video, participants stated a positive predictive value. Accuracy and speed of response were analyzed.

Results

Communicating with Bayesian information led to participant performance of only 10% (without frequency net) and 37% (with frequency net) accuracy. The tasks communicated with diagnostic information but without a frequency net were correctly solved by 72% of participants, but accuracy rate decreased to 61% when participants were given a frequency net. Participants with correct responses in the Bayesian information version without visualization took longest to complete the tasks (median of 106 seconds; median of 13.5, 14.0, and 14.5 seconds in other versions).

Discussion

Communicating with diagnostic information rather than Bayesian information helps patients to understand specific information better and more quickly. Patients’ understanding of the relevance of test results is strongly dependent on the way the information is presented.
Synanthropy and ecological aspects of Calliphoridae and Mesembrinellidae (Diptera: Oestroidea) in three ecological areas in Rio de Janeiro State, Brazil
Authors: Nunes Mariana dos Passos , Azevedo Wellington Thadeu de Alcantara , da Silva Alexandre Sousa , Lessa Cláudia Soares dos Santos , Alencar Jeronimo , Aguiar Valéria Magalhães
Published: June 2023

The determination of the synanthropic index is essential to evaluate the degree of association between species, such as diptera and man, based solely on their degree of preference for urban areas. This research aimed to study the synanthropic behavior of Calliphoridae and Mesembrinellidae flies in Rio de Janeiro, Brazil. The experiment was conducted between 2021 and 2022 in three areas, where four traps containing 300 g of fresh liver or with 48 h of putrefaction were installed, remaining exposed for 48 h; after collection the dipterans were sacrificed and taxonomically identified. A total of 2,826 dipterans were collected, represented by nine species of Calliphoridae (89.24%) and ten of Mesembrinellidae (10.76%), with the first record of Mesembrinella currani in this biome. The Kruskal-Wallis test showed that the abundance of individuals did not differ among the three analyzed environments. The Mesembrinellidae family was exclusively asynanthrope, along with two species of Calliphoridae: Hemilucilia benoisti (Séguy 1925) and Paralucilia nigrofacialis (Mello 1969) which were exclusive of the forest area, while Calliphoridae had varied synanthropy. Lucilia eximia (Wiedemann 1819) alone represented 57.18% of the total sampled, being the most abundant in all environments except the urban area where Hemilucilia segmentaria (Fabricius 1805) totaled 55.73%. No species were exclusive to the urban area, however Cochliomyia hominivorax (Coquerel 1858) and Lucilia cuprina (Wiedemann 1830) were exclusive to the rural area. The most synanthropic species were Chrysomya megacephala (Fabricius 1794) and Chrysomya albiceps (Wiedemann 1819).
Geographical specific association between lifestyles and multimorbidity among adults in China
Authors: Rong Peixi , Chen Yukui , Dang Yusong , Duan Xinyu , Yan Mingxin , Zhao Yaling , Chen Fangyao , Zhou Jing , Wang Duolao , Pei Leilei
Published: June 2023

The relationship between lifestyles and multimorbidity is well established, but previous studies have often neglected the role of spatial heterogeneity. Thus, this study is the first to explore this association in Chinese adults from a spatial perspective using a geographically weighted logistic regression (GWLR) model and describe the geographical characteristics across different regions. According to 2018 China Health and Retirement Longitudinal Study (CHARLS) database, a total of 7101 subjects were finally included, with 124 prefecture-level administrative regions in China. Non-spatial and GWLR model were used for analysis, and gender stratification analysis was also performed. Data were visualized through ArcGIS 10.7. The results showed that a total prevalence of approximately 5.13% of multimorbidity, and among participants with multimorbidity, the separate prevalence of hypertension, diabetes or high blood sugar, heart disease, and stroke were 4.45%, 2.32%, 3.02%, and 1.41%, respectively. The GWLR model indicated that current (OR: 1.202–1.220) and former smokers (OR: 1.168–1.206) may be important risk factors for multimorbidity in adults, especially in north and west among male. Past drinkers (OR: 1.233–1.240), especially in eastern China, contribute to the development of the multimorbidity in men but not in women. Vigorous-intensity activities (OR: 0.761–0.799) were negatively associated with multimorbidity in the west, with no gender difference. Depression (OR: 1.266–1.293) appeared to increase the risk for multimorbidity, with the weakest effects in central China and no gender difference. There was an interaction between light activities and gender (P = 0.024). The prevalence of multimorbidity differed across various areas of the province. The role of geographical variations in lifestyles and multimorbidity may provide valuable information for developing site-specific intervention strategies.