bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Evaluation of NTX-301, a Novel DNA Hypomethylating Agent in Ovarian Cancer
Authors: Wang Yinu , Situ Xiaolei , Cardenas Horacio , Siu Ellie , Alhunayan Sayedabdulrazzaq A. , Keathley Russell , Tanner Edward , Wei Jian-Jun , Tan Yuying , Prabhu Dessai Chinmayee Vallabh , Cheng Ji-Xin , Matei Daniela 
Published: January 2024

Abstract

Purpose:
DNA methylation causes silencing of tumor-suppressor and differentiation-associated genes, being linked to chemoresistance. Previous studies demonstrated that hypomethylating agents (HMA) resensitize ovarian cancer to chemotherapy. NTX-301 is a highly potent and orally bioavailable HMA, in early clinical development.

Experimental Design:
The antitumor effects of NTX-301 were studied in ovarian cancer models by using cell viability, stemness and ferroptosis assays, RNA sequencing, lipidomic analyses, and stimulated Raman spectroscopy.

Results:
Ovarian cancer cells (SKOV3, IC50 = 5.08 nmol/L; OVCAR5 IC50 = 3.66 nmol/L) were highly sensitive to NTX-301 compared with fallopian tube epithelial cells. NTX-301 downregulated expression of DNA methyltransferases 1–3 and induced transcriptomic reprogramming with 15,000 differentially expressed genes (DEG, P &lt; 0.05). Among them, Gene Ontology enrichment analysis identified regulation of fatty acid biosynthesis and molecular functions related to aldehyde dehydrogenase (ALDH) and oxidoreductase, known features of cancer stem cells. Low-dose NTX-301 reduced the ALDH(+) cell population and expression of stemness-associated transcription factors. Stearoyl-coenzyme A desaturase 1 (SCD), which regulates production of unsaturated fatty acids (UFA), was among the top DEG downregulated by NTX-301. NTX-301 treatment decreased levels of UFA and increased oxidized lipids, and this was blunted by deferoxamine, indicating cell death via ferroptosis. NTX-301–induced ferroptosis was rescued by oleic acid. In vivo, monotherapy with NTX-301 significantly inhibited ovarian cancer and patient-derived xenograft growth (P &lt; 0.05). Decreased SCD levels and increased oxidized lipids were detected in NTX-301–treated xenografts.

Conclusions:
NTX-301 is active in ovarian cancer models. Our findings point to a new mechanism by which epigenetic blockade disrupts lipid homeostasis and promotes cancer cell death.
Translating Science into Survival: Report on the Seventh International Cancer Immunotherapy Conference
Authors: Beck Jan D. , Kenski Juliana , Perrone Milena , Pocaterra Arianna , Honey Karen 
Published: January 2024

Abstract
From September 20 to 23, 2023, the Seventh International Cancer Immunotherapy Conference was hosted jointly by the Cancer Research Institute, the European Network for Cancer Immunotherapy (ENCI), and the American Association for Cancer Research (AACR) in Milan, Italy. The four-day event covered the latest advances in cancer immunology and immunotherapy.
Synergistic Drug Combinations Promote the Development of Resistance in Acute Myeloid Leukemia
Authors: Mason-Osann Emily , Pomeroy Amy E. , Palmer Adam C. , Mettetal Jerome T. 
Published: January 2024

Abstract

Combination therapy is an important part of cancer treatment and is often employed to overcome or prevent drug resistance. Preclinical screening strategies often prioritize synergistic drug combinations; however, studies of antibiotic combinations show that synergistic drug interactions can accelerate the emergence of resistance because resistance to one drug depletes the effect of both. In this study, we aimed to determine whether synergy drives the development of resistance in cancer cell lines using live-cell imaging. Consistent with prior models of tumor evolution, we found that when controlling for activity, drug synergy is associated with increased probability of developing drug resistance. We demonstrate that these observations are an expected consequence of synergy: the fitness benefit of resisting a drug in a combination is greater in synergistic combinations than in nonsynergistic combinations. These data have important implications for preclinical strategies aiming to develop novel combinations of cancer therapies with robust and durable efficacy.

Significance:
Preclinical strategies to identify combinations for cancer treatment often focus on identifying synergistic combinations. This study shows that in AML cells combinations that rely on synergy can increase the likelihood of developing resistance, suggesting that combination screening strategies may benefit from a more holistic approach rather than focusing on drug synergy.
See related commentary by Bhola and Letai, p. 81.
This article is featured in Selected Articles from This Issue, p. 80
O que as imagens fazem na antropologia?
Authors: Almeida Neto Joaquim Pereira de , Gonçalves Gabriela Lages , Souza Jeferson Bastos de , Macedo Victor Miguel Castillo de 
Published: January 2024

Esse dossiê, que reúne ensaios visuais provenientes de diferentes contextos de pesquisa, nos mostra que as imagens, além de fazerem ver, pensar, imaginar, movimentar, analisar e deduzir, materializam presenças e alianças. Os seis ensaios aqui publicados nos colocam diante de variadas formas de abordagem do uso de imagens, trazendo conjuntos de fotografias e de desenhos etnográficos, colagens, diagramas, mapas mentais e imagens de arquivo. Essas visualidades, cada uma a seu modo, permitem refletir sobre os processos de feitura da etnografia, sobre os espaços de intimidade adentrados ou restringidos durante o trabalho de campo, e ainda sobre as estratégias metodológicas usadas para fazer ver ou fazer compreender aquilo que é vivido nos encontros entre pesquisadores e interlocutores de pesquisa.
The Effects of Whole-Hand Interactions with One Fingertip Vibrotactile Feedback on Cooperative VR Game Experience and Performance
Authors: Moon Hye Sung , Moon Hayoun , Orr Grady , Jeon Myounghoon 
Published: January 2024

Abstract
New technologies have recently advanced user experiences in virtual reality (VR), whereas full sensation of diverse modalities has been not achieved yet. If any, haptic feedback has been delivered via bulky gloves. We have developed a novel thimble device that can deliver vibrotactile feedback via one fingertip. With this device, in the present study we investigated the effects of interaction methods and vibrotactile feedback on users' social presence, presence, engagement, workload, and performance in a cooperative VR game. Twenty-six participants wearing a VR headset played a cooperative VR game with the experimenter under four conditions: (1) controllers with no vibrotactile feedback, (2) controllers with vibrotactile feedback, (3) hand tracking with no vibrotactile feedback, and (4) hand tracking with vibrotactile feedback. Results showed that hand tracking improved participants' presence, engagement, and perceived workload compared to the traditional VR controllers. Also, vibrotactile feedback enhanced presence. However, the VR controllers outperformed the hand tracking interactions in completion time. The usability of hand interactions with vibrotactile feedback shows a promising result. We discuss the trade-offs between user experience and performance of the interaction methods and the potential of vibrotactile feedback in the VR environment.
The Latin Polycarp, the Division Hypothesis, and Polylingual Text
Authors: Gasse Grant W. 
Published: January 2024

Abstract
Polycarp’s Letter to the Philippians (Pol.Phil.) is poorly attested. All extant Greek manuscripts (G) stem from one source, Vaticanus Graecus 859 (V), which preserves only a portion of the text. Accordingly, editors reproduce G, supplemented as needed with the old Latin translation (L), preserved in its entirety, and with Greek fragments preserved in Eusebius. I argue that L ought to be treated as a discrete witness to the epistle, and not merely as supplement to G. The paper proceeds in two parts: first, I offer a careful analysis of the translation, concluding that L offers a relatively faithful, literal translation and a comparably well-preserved attestation to the epistle. Second, I demonstrate that the well-known “division hypothesis” relies upon an incomplete analysis of L. In short, I contend that the construction of composite, polylingual critical editions of Pol.Phil. has occasioned textual problemata unreflected in the text’s individual manuscript traditions.
Effects of Otago exercise programme and Pilates based exercise to minimise risk of fall in older adult women of the rural population of Haryana
Authors: Kashish B. , Hussain M.E. , Kumar S. 
Published: January 2024

Abstract
Older adults frequently experience falls, which is a serious issue that can have severe effects on both the individual and society. Physiotherapy can play an important role in older persons to avoid falling. The objective of the current study is to evaluate the potential efficacy of Otago exercise and Pilates based exercise for preventing falls. On the basis of inclusion criteria 75 older adult women were randomly assigned into three groups, i.e. Group A (Otago exercise group), Group B (Pilates exercise group) and Group C (Control group). Mobility, fear of fall, activities of daily living, balance and sleep quality were examined at baseline and after 6 weeks of the intervention. Otago exercise group session was administered for 30 min per day, at a frequency of 5 sessions per week, for a period of 6 weeks, whereas Pilates based exercise group session was for 30 min., 3 days/week for 6 weeks. There was a significant difference in time up and go test score (), fall efficacy scale (), Berg balance scale (), whereas no or minimal significant was the Barthel index score (). Sleep quality improved by Pilates based exercise () more than other groups. Main findings of the present study suggest that Otago exercise program improve mobility, activity of daily living, balance, decrease fear of fall and Pilates can be used to improve sleep.
Self-Reported Mood and Lifestyle-Related Physical Activity of Young Adults With Major Depressive Disorder
Authors: Tavares Vagner Deuel de O. , de Sousa Geovan Menezes , Schuch Felipe B. , Campanelli Stephany , Meyer Jacob , de Almeida Raissa Nóbrega , Agrícola Pedro Moraes Dutra , Alves Leonardo , Gurgel Maria Luiza , Gonçalves Kaike Thiê da Costa , Patten Scott , Sarris Jerome , Barbalho Walter , Arcoverde Emerson Nunes , Galvão-Coelho Nicole Leite 
Published: January 2024

We investigated whether mood and lifestyle-related indicators of physical health are differentially expressed according to self-reported levels of depressive symptoms among young adults with a current episode of major depression. In a cross-sectional study, we recruited 94 young adults (females = 67, 71.3%; males = 27, 28.7%; aged 18–35 years) with a current episode of major depression. We assessed their mood with the Profile of Mood States (POMS), and Beck Anxiety Inventory-(BAI), sleep with the Pittsburgh Sleep Quality Index (PSQI), physical activity with the Simple Physical Activity Questionnaire (SIMPAQ), and their cardiorespiratory fitness. Participants’ depression levels were classified as follows using established cut-points: (a) Mild Depressive Symptoms (MIDS, BDI-II 14-19 points, n = 17), (b) Moderate Depressive Symptoms (MODS, BDI-II 20–28 points, n = 37) or (c) Severe Depressive Symptoms (SEDS, BDI-II 29–63 points, n = 40). As expected, we found that young adults with SEDS, when compared to those with MODS and MIDS, showed higher depressive mood on the POMS, and they exhibited greater anxiety symptoms, lower reported ‘vigor’ on physical activity measures, worse sleep quality as expressed by their global score sleep; daytime dysfunction; and sleep disturbance, and they showed lower cardiorespiratory fitness. Those with moderate depressive symptoms only differed from those with mild symptoms with respect to hostility, fatigue and mood disturbance. Although there was a gradient whereby worse mental and physical health indicators were more closely related to the SEDS depression categorization, while healthier indicators were associated with the MIDS category, some parameters were not different between the MDD severity groups, particularly when comparing MIDS and MODS. Clinicians treating patients with MDD should consider these factors when designing lifestyle-based interventions.
Pain and Heart Failure During Transport by Emergency Medical Services and Its Associated Outcomes: Hospitalization, Mortality, and Length of Stay
Authors: Smith Asa B. , Jung Miyeon , Pressler Susan J. 
Published: January 2024

Background: Over 22% of patients with heart failure (HF) are transported by emergency medical services (EMSs) for a primary complaint of pain. The relationship between a primary complaint of pain on hospitalization status, mortality, or length of stay following transport by EMS is understudied. Objectives: The objective of this study was to determine whether a primary complaint of pain during EMS transport predicted hospitalization status, mortality, or inpatient length of stay. Methods: In this retrospective longitudinal cohort study, data were analyzed from electronic health records of 3539 patients with HF. Descriptive statistics and multivariate logistic and linear regression analyses were used to achieve study objectives. Results: Demographics were mean age 64.83 years (standard deviation [SD] = 14.58); gender 57.3% women, 42.7% men; self-reported race 56.2% black, 43.2% white, and 0.7% other. Of 3539 patients, 2346 (66.3%) were hospitalized, 149 (4.2%) died, and the mean length of stay was 6.02 (SD = 7.55) days. A primary complaint of pain did not predict increased odds of in-hospital mortality but did predict 39% lower odds of hospitalization ( p < .001), and 26.7% shorter length of stay ( p < .001). Chest pain predicted 49% lower odds of hospitalization ( p < .001) and 34.1% ( p < .001) shorter length of stay, whereas generalized pain predicted 45% lower odds of hospitalization ( p = .044) following post-hoc analysis. Conclusions: A primary complaint of chest pain predicted lower odds of hospitalization and shorter length of stay, possibly due to established treatment regimens. Additional research is needed to examine chronic pain rather than a primary complaint of pain.
Posttraumatic growth in palliative care settings: A scoping review of prevalence, characteristics and interventions
Authors: Austin Philip D , Siddall Philip J , Lovell Melanie R 
Published: January 2024

Background: Posttraumatic growth refers to positive psychological change following trauma. However, there is a need to better understand the experience of posttraumatic growth in the palliative care setting as well as the availability and efficacy of interventions that target this phenomenon. Aims: To provide a review of the prevalence, characteristics and interventions involving posttraumatic growth in adults receiving palliative care and to collate recommendations for future development and utilisation of interventions promoting posttraumatic growth. Design: We performed a systematic scoping review of studies investigating posttraumatic growth in palliative care settings using the Arksey and O'Malley six-step scoping review criteria. We used the PRISMA guidelines for scoping reviews. Data sources: Articles in all languages available on Ovid Medline [1946–2022], Embase [1947–2022], APA PsycINFO [1947–2022] and CINAHL [1981–2022] in November 2022. Results: Of 2167 articles located, 17 were included for review. These reported that most people report low to moderate levels of posttraumatic growth with a decline towards end-of-life as distress and symptom burden increase. Associations include a relationship between posttraumatic growth, acceptance and greater quality-of-life. A limited number of interventions have been evaluated and found to foster posttraumatic growth and promote significant psychological growth. Conclusion: Posttraumatic growth is an emerging concept in palliative care where although the number of studies is small, early indications suggest that interventions fostering posttraumatic growth may contribute to improvements in psychological wellbeing in people receiving palliative care.
Outcomes and Return-to-Sports Rates in Patients With Borderline Hip Dysplasia After Periacetabular Osteotomy: A Case Series With 5-Year Follow-up
Authors: Leopold Vincent J. , Szarek Adrian , Hipfl Christian , Bärtl Susanne , Perka Carsten , Hardt Sebastian 
Published: January 2024

Background: The optimal surgical approach in patients with borderline hip dysplasia (BHD) remains controversial. Both hip arthroscopy and periacetabular osteotomy (PAO) are commonly employed in this patient population. Those who participate in sports want to resume and maintain sports activities after surgery, and the ability to do so plays an important role in the choice of a treatment method. To our knowledge, no previous study has assessed return-to-sports rates and activity levels in patients with BHD after PAO. Purpose: To assess return-to-sports rates and postoperative activity levels as measured by the University of California, Los Angeles (UCLA), activity scale as well as patient-reported outcome measures. Also to assess changes in sports activity both qualitatively and quantitatively as well as underlying reasons for these changes. Study Design: Case series; Level of evidence, 4. Methods: We conducted a retrospective analysis of prospectively collected data from 55 hips in 52 patients with BHD who underwent PAO between January 2015 and June 2017. Return-to-sports rates, UCLA activity scores, International Hip Outcome Tool–12 scores, Subjective Hip Value scores, Hip disability and Osteoarthritis Outcome Score subscores, sports practiced, frequency and duration of sports activity, and postoperative changes as well as underlying reasons were recorded. Results: The mean follow-up was 62.8 ± 9.0 months. The return-to-sports rate among preoperatively active patients was 92.5%. Most patients resumed sports activity after 6 months (50%) or after 3 to 6 months (37.5%). The UCLA activity score improved significantly (from 5.2 ± 2.4 to 7.0 ± 1.8; P < .001). The International Hip Outcome Tool-12, Subjective Hip Value, and Hip disability and Osteoarthritis Outcome Score scores also improved significantly (all, P < .001). Changes in sports activity occurred in 34.5% of cases after PAO. Significantly more patients engaged in low-impact sports postoperatively. Participation in high-impact sports did not decrease significantly. Reasons for changes were both hip related and non–hip related. Quantitatively, patients were able to significantly increase both the frequency ( P = .007) and duration ( P = .007) of sports activity. Conclusion: The return-to-sports rate in patients with BHD after PAO was high at over 92%. Most patients returned to sports after a period of 6 months or 3 to 6 months. Overall, activity levels and hip function improved after PAO. A number of patients adjusted their sports activity after PAO. Although more patients engaged in low-impact sports, participation in high-impact sports was maintained postoperatively. The results of this study may help both patients and orthopaedic surgeons in deciding on the best surgical procedure in the setting of BHD.
Citrate anticoagulation in plasma exchange followed by continuous renal replacement therapy in critically ill children
Authors: Xinping Zhang , Jie He , Zhenya Yao , Desheng Zhu , Xiong Zhou 
Published: January 2024

Objective: To investigate the effectiveness and safety of regional citrate-anticoagulated (RCA) plasma exchange (PE) and whether citrate-related metabolic disorders can be improved by sequential RCA continuous renal replacement therapy (CRRT). Methods: This retrospective, single-center observational study included 79 critically ill children requiring PE followed by CRRT (June 2018 to June 2021) at the Pediatric Intensive Care Unit of Hunan Children’s Hospital, China. Patients were divided into the RCA-PE ( n = 30) and systemic heparin anticoagulation (SHA-PE) ( n = 49) groups. Filter level comparison post-PE assessed RCA-PE efficacy, and metabolic changes occurring pre- and post-PE and CRRT were used to evaluate the effect of CRRT on RCA-based anticoagulation safety. Results: The RCA-PE group had a better overall filter performance than the SHA-PE group. Two hours after PE, pH and HCO₃− levels increased more significantly for the RCA-PE than the SHA-PE group. The RCA-PE incidence of metabolic alkalosis was 48.3%, higher by 4.2% ( p < 0.001) compared to the SHA-PE group. In the RCA-PE group, pH and HCO₃− decreased significantly 4 h after CRRT; the metabolic alkalosis caused by RCA-PE decreased to 13.8% ( p = 0.005). No significant difference in pH, HCO₃−, and metabolic alkalosis incidence was observed between the two groups 4 h after CRRT. Conclusions: The overall filtration performance of RCA-PE is superior to that of SHA-PE followed by CRRT. The metabolic complications associated with RCA-PE are mainly metabolic alkalosis that can be improved by using CRRT after RCA-PE and this is a better alternative for anticoagulation during PE in critically ill children.
Psychological Distress and Treatment Outcome in Patients With Early-Stage Mycosis Fungoides
Authors: Henderson Berg Meagan-Helen , Popradi Gizelle , Roberge David , Petrogiannis-Haliotis Tina , Pehr Kevin 
Published: January 2024

Background: Skin diseases have been shown to worsen psychological distress, which, in turn, may be detrimental to treatment outcomes. Both the impact of psychological distress on response to treatment in mycosis fungoides (MF) and the effect of treatments on psychological well-being are unclear. Objectives: To evaluate (1) the association between pretreatment psychological morbidity and treatment outcome in early-stage MF and (2) the impact of response to treatment on psychological well-being. Methods: This was a prospective cohort study of patients with early-stage MF who started a new stage-directed treatment for their disease. The response was determined using the modified severity-weighted assessment tool, and psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12) and Penn State Worry Questionnaire (PSWQ). Participants were followed for 1 year. Results: In all, 24 consecutive patients were recruited. Objective response rate was 71% (17/24), consistent with existing literature. Prior to treatment, 9 patients (38%) had clinically significant psychological distress on the GHQ-12, while 8 (33%) demonstrated high-level worry on the PSWQ. Of these patients, 6 had pathologic scores on both instruments. Patients with significantly less baseline anxiety/depression on the GHQ-12 responded better to treatment than patients with higher levels ( P = .004). In addition, responders’ mean GHQ-12 scores decreased by 39% and their PSWQ scores by 17%, whereas nonresponders’ GHQ-12 scores increased by 93% ( P = .042) and their PSWQ scores by 11% ( P = .019). Conclusions: These findings suggest that (1) baseline psychological distress is associated with worse outcomes in patients with early-stage MF and that (2) effective treatment improves psychological morbidity.