bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition and reversal of a TGF-β1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors
Authors: Higginbotham S. , Workman V. L. , Giblin A-V. , Green N. H. , Lambert D. W. , Hearnden V.
Published: June 2024

Background

Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation.

Methods

The transforming growth factor-β1 (TGF-β1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts.

Results

Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-β1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue.

Conclusions

Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism.
Endogenous stem cell mobilization and localized immunosuppression synergistically ameliorate DSS-induced Colitis in mice
Authors: Regmi Shobha , Pathak Shiva , Chaudhary Dinesh , Kim Jong Oh , Nam Joo-Won , Kim Hyung-Sik , Jiang Hu-Lin , Ryu Dongryeol , Sung Jong-Hyuk , Yook Simmyung , Jeong Jee-Heon
Published: June 2024

Background

Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases.

Methods

Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR.

Results

The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process.

Conclusion

This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.
Differently different?: A commentary on the emerging social cognitive neuroscience of female autism
Authors: Rippon Gina
Published: June 2024

Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males. This observed preponderance of males in autistic populations has served as a focussing framework in all spheres of autism-related issues, from recognition and diagnosis through to theoretical models and research agendas. One related issue is the near total absence of females in key research areas. For example, this paper reports a review of over 120 brain-imaging studies of social brain processes in autism that reveals that nearly 70% only included male participants or minimal numbers (just one or two) of females. Authors of such studies very rarely report that their cohorts are virtually female-free and discuss their findings as though applicable to all autistic individuals. The absence of females can be linked to exclusionary consequences of autism diagnostic procedures, which have mainly been developed on male-only cohorts. There is clear evidence that disproportionately large numbers of females do not meet diagnostic criteria and are then excluded from ongoing autism research. Another issue is a long-standing assumption that the female autism phenotype is broadly equivalent to that of the male autism phenotype. Thus, models derived from male-based studies could be applicable to females. However, it is now emerging that certain patterns of social behaviour may be very different in females. This includes a specific type of social behaviour called camouflaging or masking, linked to attempts to disguise autistic characteristics. With respect to research in the field of sex/gender cognitive neuroscience, there is emerging evidence of female differences in patterns of connectivity and/or activation in the social brain that are at odds with those reported in previous, male-only studies. Decades of research have excluded or overlooked females on the autistic spectrum, resulting in the construction of inaccurate and misleading cognitive neuroscience models, and missed opportunities to explore the brain bases of this highly complex condition. A note of warning needs to be sounded about inferences drawn from past research, but if future research addresses this problem of male bias, then a deeper understanding of autism as a whole, as well as in previously overlooked females, will start to emerge.
Aurora Kinase A inhibition enhances DNA damage and tumor cell death with 131I-MIBG therapy in high-risk neuroblastoma
Authors: Kumar Prerna , Koach Jessica , Nekritz Erin , Mukherjee Sucheta , Braun Benjamin S. , DuBois Steven G. , Nasholm Nicole , Haas-Kogan Daphne , Matthay Katherine K. , Weiss William A. , Gustafson Clay , Seo Youngho
Published: June 2024

Background

Neuroblastoma is the most common extra-cranial pediatric solid tumor. 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical highly specific for neuroblastoma tumors, providing potent radiotherapy to widely metastatic disease. Aurora kinase A (AURKA) plays a role in mitosis and stabilization of the MYCN protein in neuroblastoma. We aimed to study the impact of AURKA inhibitors on DNA damage and tumor cell death in combination with 131I-MIBG therapy in a pre-clinical model of high-risk neuroblastoma.

Results

Using an in vivo model of high-risk neuroblastoma, we demonstrated a marked combinatorial effect of 131I-MIBG and alisertib on tumor growth. In MYCN amplified cell lines, the combination of radiation and an AURKA A inhibitor increased DNA damage and apoptosis and decreased MYCN protein levels.

Conclusion

The combination of AURKA inhibition with 131I-MIBG treatment is active in resistant neuroblastoma models.
New improved radiometabolite analysis method for [18F]FTHA from human plasma: a test-retest study with postprandial and fasting state
Authors: Aarnio Richard , Kirjavainen Anna , Rajander Johan , Forsback Sarita , Kalliokoski Kari , Nuutila Pirjo , Milicevic Zvonko , Coskun Tamer , Haupt Axel , Laitinen Iina , Haaparanta-Solin Merja
Published: June 2024

Background

Fatty acid uptake can be measured using PET and 14-(R,S)‐[18F]fluoro‐6‐thia‐heptadecanoic acid ([18F]FTHA). However, the relatively rapid rate of [18F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [18F]FTHA (parent fraction). Here we present a new radiometabolite analysis (RMA) method, with comparison to a previous method for parent fraction analysis, and its use in a test-retest clinical study under fasting and postprandial conditions. We developed a new thin-layer chromatography (TLC) RMA method for analysis of [18F]FTHA parent fraction and its radiometabolites from plasma, by testing stationary phases and eluent combinations. Next, we analyzed [18F]FTHA, its radiometabolites, and plasma radioactivity from subjects participating in a clinical study. A total of 17 obese or overweight participants were dosed with [18F]FTHA twice under fasting, and twice under postprandial conditions and plasma samples were obtained between 14 min (mean of first sample) and 72 min (mean of last sample) post-injection. Aliquots of 70 plasma samples were analyzed using both methods, enabling head-to-head comparisons. We performed test-retest and group comparisons of the parent fraction and plasma radioactivity.

Results

The new TLC method separated seven [18F]FTHA radiometabolite peaks, while the previous method separated three. The new method revealed at least one radiometabolite that was not previously separable from [18F]FTHA. From the plasma samples, the mean parent fraction value was on average 7.2 percentage points lower with the new method, compared to the previous method. Repeated [18F]FTHA investigations on the same subject revealed reproducible plasma SUV and parent fractions, with different kinetics between the fasted and postprandial conditions.

Conclusions

The newly developed improved radio-TLC method for [18F]FTHA RMA enables accurate parent fraction correction, which is required to obtain quantitative data for modelling [18F]FTHA PET data. Our test-retest study of fasted and postprandial conditions showed robust reproducibility, and revealed clear differences in the [18F]FTHA metabolic rate under different study settings.

Trial registration

EudraCT No: 2020-005211-48, 04Feb2021; and Clinical Trials registry NCT05132335, 29Oct2021, URL: https://classic.clinicaltrials.gov/ct2/show/NCT05132335.
Development and application of a risk nomogram for the prediction of risk of carbapenem-resistant Acinetobacter baumannii infections in neuro-intensive care unit: a mixed method study
Authors: Li Yuping , Gao Xianru , Diao Haiqing , Shi Tian , Zhang Jingyue , Liu Yuting , Zeng Qingping , Ding JiaLi , Chen Juan , Yang Kai , Ma Qiang , Liu Xiaoguang , Yu Hailong , Lu Guangyu
Published: June 2024

Objective

This study aimed to develop and apply a nomogram with good accuracy to predict the risk of CRAB infections in neuro-critically ill patients. In addition, the difficulties and expectations of application such a tool in clinical practice was investigated.

Methods

A mixed methods sequential explanatory study design was utilized. We first conducted a retrospective study to identify the risk factors for the development of CRAB infections in neuro-critically ill patients; and further develop and validate a nomogram predictive model. Then, based on the developed predictive tool, medical staff in the neuro-ICU were received an in-depth interview to investigate their opinions and barriers in using the prediction tool during clinical practice. The model development and validation is carried out by R. The transcripts of the interviews were analyzed by Maxqda.

Results

In our cohort, the occurrence of CRAB infections was 8.63% (47/544). Multivariate regression analysis showed that the length of neuro-ICU stay, male, diabetes, low red blood cell (RBC) count, high levels of procalcitonin (PCT), and number of antibiotics ≥ 2 were independent risk factors for CRAB infections in neuro-ICU patients. Our nomogram model demonstrated a good calibration and discrimination in both training and validation sets, with AUC values of 0.816 and 0.875. Additionally, the model demonstrated good clinical utility. The significant barriers identified in the interview include “skepticism about the accuracy of the model”, “delay in early prediction by the indicator of length of neuro-ICU stay”, and “lack of a proper protocol for clinical application”.

Conclusions

We established and validated a nomogram incorporating six easily accessed indicators during clinical practice (the length of neuro-ICU stay, male, diabetes, RBC, PCT level, and the number of antibiotics used) to predict the risk of CRAB infections in neuro-ICU patients. Medical staff are generally interested in using the tool to predict the risk of CRAB, however delivering clinical prediction tools in routine clinical practice remains challenging.
Seabirds show foraging site and route fidelity but demonstrate flexibility in response to local information
Authors: Regan Charlotte E. , Bogdanova Maria I. , Newell Mark , Gunn Carrie , Wanless Sarah , Harris Mike P. , Lopez Samuel Langlois , Benninghaus Ella , Bolton Mark , Daunt Francis , Searle Kate R.
Published: June 2024

Background

Fidelity to a given foraging location or route may be beneficial when environmental conditions are predictable but costly if conditions deteriorate or become unpredictable. Understanding the magnitude of fidelity displayed by different species and the processes that drive or erode it is therefore vital for understanding how fidelity may shape the demographic consequences of anthropogenic change. In particular, understanding the information that individuals may use to adjust their fidelity will facilitate improved predictions of how fidelity may change as environments change and the extent to which it will buffer individuals against such changes.

Methods

We used movement data collected during the breeding season across eight years for common guillemots, Atlantic puffins, razorbills, and black-legged kittiwakes breeding on the Isle of May, Scotland to understand: (1) whether foraging site/route fidelity occurred within and between years, (2) whether the degree of fidelity between trips was predicted by personal foraging effort, and (3) whether different individuals made more similar trips when they overlapped in time at the colony prior to departure and/or when out at sea suggesting the use of the same local environmental cues or information on the decisions made by con- and heterospecifics.

Results

All species exhibited site and route fidelity both within- and between-years, and fidelity between trips in guillemots and razorbills was related to metrics of foraging effort, suggesting they adjust fidelity to their personal foraging experience. We also found evidence that individuals used local environmental cues of prey location or availability and/or information gained by observing conspecifics when choosing foraging routes, particularly in puffins, where trips of individuals that overlapped temporally at the colony or out at sea were more similar.

Conclusions

The fidelity shown by these seabird species has the potential to put them at greater risk in the face of environmental change by driving individuals to continue using areas being degraded by anthropogenic pressures. However, our results suggest that individuals show some flexibility in their fidelity, which may promote resilience under environmental change. The benefits of this flexibility are likely to depend on numerous factors, including the rapidity and spatial scale of environmental change and the reliability of the information individuals use to choose foraging sites or routes, thus highlighting the need to better understand how organisms combine cues, prior experience, and other sources of information to make movement decisions.
The mRNA surveillance factor Pelo restricts rice virus propagation in insect vectors and host plants
Authors: Sun Xinyan , Guan Heran , Wei Taiyun , Jia Dongsheng
Published: June 2024

Many devastating plant viruses are transmitted by insect vectors among plant hosts in a persistent-propagative manner. Pelota (Pelo) is an evolutionarily conserved protein involved in the mRNA surveillance system. In this study, it was found that the accumulation of Pelo proteins are slightly decreased during the propagation of the fijivirus southern rice black-streaked dwarf virus (SRBSDV) in rice and transmission vector planthopper (Sogatella furcifera). The tubular protein P7-1 encoded by SRBSDV interacted with Pelo of rice or planthopper vector. Overexpression or knockdown of Pelo expression inhibits the formation of P7-1 tubules in insect cells, further exerting antiviral activity. Furthermore, overexpression or knockout of Pelo expression in transgenic rice plants also inhibits the effective propagation of SRBSDV as well as two other rice viruses of different families. The slight reduction of Pelo accumulation during SRBSDV propagation in rice and insect vectors would avoid Pelo-mediated excessive inhibition of P7-1 tubule formation, ensuring effective virus propagation. Our findings provide insights into how the up- or down-regulated expression of Pelo in rice hosts and insect vectors elevate their resistance to rice viruses.
Final results of a randomized phase II/III study comparing perioperative adriamycin plus ifosfamide and gemcitabine plus docetaxel for high-grade soft tissue sarcomas: Japan Clinical Oncology Group study JCOG1306.
Authors: Tanaka Kazuhiro , Machida Ryunosuke , Endo Makoto , Kawai Akira , Nakayama Robert , Tsukushi Satoshi , Asanuma Kunihiro , Hiraga Hiroaki , Hiraoka Koji , Yoshida Shinichiro , Yonemoto Tsukasa , Imanishi Jungo , Katagiri Hirohisa , Nishida Yoshihiro , Nagano Akihito , Sekino Yuta , Fukuda Haruhiko , Ozaki Toshifumi , Iwamoto Yukihide ,   JCOG Bone and Soft Tissue Tumor Study Group
Published: June 2024

11503

Background: We have previously reported long-term follow-up results of the favorable efficacy of perioperative chemotherapy with adriamycin plus ifosfamide (AI) for high-grade soft tissue sarcomas (STS) (JCOG0304). We have also reported the results of the second interim analysis of a phase II/III trial to confirm the non-inferiority of perioperative gemcitabine plus docetaxel (GD) to AI for high-grade STS (JCOG1306) in 2020 ASCO Annual Meeting. This study was terminated at the preplanned second interim analysis based on the point estimate of hazard ratio (HR) being above the pre-specified allowable HR of 1.61. The estimated 2-year overall survival (OS) was 94.3% (95% confidence interval (CI) 83.4–98.1%) in AI and 91.6% (80.9–96.4%) in GD (HR 2.55, 95% CI 0.80–8.14) in the analysis. We herein report the final results of JCOG1306 at 5-year follow-up. Methods: Patients with operable, FNCLCC grade 2/3 STS primary tumor (T2bN0M0 or anyTN1M0, AJCC 7th edition) or first local recurrent tumor in the extremities or trunk were randomized to AI or GD. Chemotherapy consisted of adriamycin 60 mg/m2 plus ifosfamide 10 g/m2 for AI or gemcitabine 1,800 mg/m2 plus docetaxel 70 mg/m2 for GD. The treatments were repeated for 3 courses preoperatively and 2 courses postoperatively in a 3-week interval. The primary endpoint in phase III part was OS. Planned sample size was 140 with a one-sided alpha of 0.1, power of 0.7 and a non-inferiority margin of 8% at 3-year OS (HR of 1.61), assuming 3-year OS of AI to be 85% and that of GD as 87%. Results: A total of 143 patients were enrolled between February 2014 and September 2018, and 5-year follow-up has finished in September 2023. Seventy and 73 patients were assigned to AI and GD, respectively, and included in the efficacy analysis. At the final analysis with a median follow-up of 6.0 years, the estimated 5-year OS was 90.0% (95% CI 80.1–95.1%) in AI and 76.1% (64.5–84.4%) in GD (HR 2.67, 95% CI 1.23–5.80). The estimated 5-year progression-free survival was 65.2% (95% CI: 52.7–75.2%) in AI and 57.4% (45.2–67.8%) in GD (HR: 1.33, 95% CI 0.81–2.18). At the 5-year follow-up analysis, there were no treatment-related deaths in both arms. Conclusions: The results of the second interim analysis were confirmed in the final analysis after five-year follow-up, i.e., non-inferiority of GD to AI in terms of OS could not be confirmed. In the perioperative chemotherapy for high-grade STS in the extremities and trunk, AI remains the standard regimen. Clinical trial information: jRCTs031180003 .
Functional impairments, fatigue, and pain in newly diagnosed solid-tumors: Retrospective path analysis.
Authors: Beeler Dori Michelle , Boselli Danielle , Meadors Patrick L. , Walsh Declan
Published: June 2024

12066

Background: A large patient cohort study found functional impairments (FI) are associated with cancer-related fatigue (CRF). This was before anti-cancer treatment for solid tumors. Another found functional limitations increased with self-reported pain severity. We hypothesize that both (a) a direct association between pain and CRF and (b) an indirect association between the symptoms through a mediation pathway involving FI may exist. Our retrospective, single-institutional study evaluated this model. Methods: We sourced Electronic Distress Screening (EDS) and Cancer Registry databases (Jan 2017 - Jan 2022). Patients identified were ≥18 years old and completed EDS within two (±2) weeks of a solid tumor diagnosis and before any anti-cancer therapy. Three EDS questions assessed FI with a two-week recall: 1) “How well have you managed your daily life?”; 2) “Has your physical health kept you from doing things like household chores or climbing stairs?”; 3) “Do you have limited movement in any body part?”. Pain and CRF were assessed on a numerical rating scale [0 (none) to 10 (worst possible)]. Structural equation modeling tested the multiple mediation model. The 95% confidence intervals of the estimated total and FI domain-specific indirect effects, the effects of pain on CRF working through FI, were assessed to exclude zero. Results: N=4326. Median age = 63 years (range 18 - 97); 69% female and 78% White. The commonest tumor site groups were breast (30%), upper GI (17%), and gynecologic (16%); 21% had Stage 4 disease. Median CRF was 4 (range 0-10); 57% had clinically significant CRF (fatigue ≥4). Median pain was 3 (range 0-10); 51% had clinically significant pain (pain ≥3). A significant minority had FI. N=753 (17%) had either “very poor” or “fairly poor” management of day-to-day life. N=778 (18%) had “a lot” of difficulty in performing chores. N=1252 (29%) had limited movement of any body part. FI partially mediated the pain/CRF relationship (indirect effect (IEtotal)=0.25, 95% CI 0.24-0.27). Two mediators had statistically significant contributions to the total indirect effect: management of daily life (IEmanage=0.12, 95% CI 0.11-0.13); and difficulty in performing chores (IEchores=0.13, 95% CI 0.11-0.14). The limited movement of any body part did not impact the pain/CRF relationship (IEmovement=-0.01, 95% CI -0.01-0.01). Conclusions: Most patients had clinically significant pain and CRF at diagnosis. A significant minority had FI at diagnosis. FI partially mediated the direct relationship between pain/CRF severity. This helps us understand that FI accounts for some of the relationship between pain and CRF. It is insufficient to conduct symptom assessments without also evaluating FI before treatment or at diagnosis.
Fertility and Pregnancy Outcomes in Primary Hyperparathyroidism: Observations From a Large Insured Population
Authors: Sant Vivek R , Zhou Hui , Zhou Mengnan M , Adams Annette L , Ryan Denison S , Case Samuel K , Seo Young-Ji , Haigh Philip I , Janzen Carla , Yeh Michael W
Published: June 2024

Context

Primary hyperparathyroidism (PHPT) has initially been implicated in adverse maternal and neonatal outcomes, while subsequent population studies have failed to show an association.

Objective

This work aimed to compare maternal, pregnancy, and neonatal outcomes in patients with and without PHPT.

Methods

A retrospective matched-cohort study (2005-2020) was conducted at an integrated health-care delivery system in Southern California. Women aged 18 to 44 years were included. Patients with a biochemical diagnosis of PHPT were matched 1:3 with eucalcemic controls (non-PHPT). Main outcome measures included achievement of pregnancy, pregnancy outcomes (including rates of abortion, maternal complications), and neonatal outcomes (including hypocalcemia, need for intensive care).

Results

The cohort comprised 386 women with PHPT and 1158 age-matched controls. Pregnancy rates between PHPT and control groups were similar (10.6% vs 12.8%). The adjusted rate ratio of pregnancy was 0.89 (95% CI, 0.64-1.24) (PHPT vs non-PHPT). Twenty-nine pregnancies occurred in women with coexisting PHPT and 191 pregnancies occurred in controls, resulting in 23 (79.3%) and 168 (88.0%) live births, respectively (P = .023). Neonatal outcomes were similar. Live birth rates were similar (86.4%, 80%, 79.2%) for those undergoing parathyroidectomy prior (n = 22), during (n = 5), or after pregnancy/never (n = 24). Among patients who underwent parathyroidectomy during pregnancy, no spontaneous abortions occurred in women entering pregnancy with peak calcium less than 11.5 mg/dL (2.9 mmol/L).

Conclusion

We observed no difference in pregnancy rates between women with or without PHPT. Performing parathyroidectomy before pregnancy or during the second trimester appears to be a safe and successful strategy, and adherence to this strategy may be most critical for patients with higher calcium levels (≥11.5 mg/dL [2.9 mmol/L]).
Introduction
Authors: Nuttall Sarah
Published: June 2024

This chapter introduces Penny Siopis’s films to the reader, situates her as a South African artist and filmmaker and thereafter places her work in relation to wider cinematic traditions of thought and practice, including the essay film genre, cinécriture, Third Cinema, and African diasporic short film traditions. Reflections on the essay form by Theodor Adorno are drawn in as are Gilles Deleuze’s writing on the “irrational cut” as a mode that attempts to capture something of the movement of thought itself. These are in turn placed in conversation with the new work generated by the contributors to the book itself: writers, scholars, curators, filmmakers, and artists. The introduction draws out the signal arguments of each chapter to offer the reader an overview of the emerging field of Siopis scholarship and engagement. Penny Siopis’s almost exclusive use of found footage, her refusal of the device of the voiceover and her profound reworking of relations between word, sound, and image are foregrounded as radical contributions to the histories of film today, here in cosmopolitan collocation with the African South.
Encounters with the Concentrationary
Authors: Hollweg Brenda
Published: June 2024

This chapter explores the manifold ways in which Penny Siopis’s transnational essay film The New Parthenon invokes “the concentrationary” (David Rousset): a logic of destruction and violation against the human that did not vanish with the defeat of Nazi Germany or the end of the Second World War but is still pervasive today, even, as it becomes increasingly visible, in countries that call themselves “democratic.” Drawing on Jean Cayrol’s notion of “Lazarean art,” an art of the in-between, the chapter traces the suggestive ways in which Siopis’s audiovisual essay—not a film about concentration camps proper, not even about a particular camp—both invokes and enables viewers to resist “concentrationary” logics. This is done via more oblique modes of correspondence, gesture, metonymy, asynchronicity, or dissonance, allowing us to move with, and be moved by, the residual resistances of the material to which the film also gives force.
Hellenic Histories
Authors: Gregos Katerina
Published: June 2024

This chapter discusses specifically Hellenic frames of reference in Penny Siopis’s films, focusing on her Greek family roots and on political events that marked the twentieth century dispersions of the Greek diaspora, including to the African continent. Theses dispersals were shaped, the chapter shows, by nearly two thousand years of Byzantine and Ottoman Empires in the Eastern Mediterranean, and by the Second World War and the Greek Civil War, among others. The analysis centers on Siopis’s first film, My Lovely Day, and its recounting of events related to the Smyrna catastrophe, on the figure of Demitrios Tsafendas, who fought with communist forces during the Greek Civil War, in Obscure White Messenger, and on several tragic waves of Greek history explored in The New Parthenon. The latter uses the partial lens of her father’s personal history, interweaving this with the rounding up of nine thousand Greeks of Jewish descent in Thessaloniki during World War II and the political imprisonment of Communists on the island of Makronisos after the Greek Civil War.
The Tapeworm Writes Back!
Authors: Gevisser Mark
Published: June 2024

The chapter discusses Penny Siopis’s “tentacular art,” beginning with She Breathes Water and considering other cameo appearances of the octopus figure/footage in previous films and well as the significance of water, swimming, and diving in Siopis’s film work. A close reading of Obscure White Messenger reveals Siopis’s association between the degraded celluloid of the aquarium octopus footage (the octopus as Tsafendas’s “tapeworm”) and the synaptic disturbances of a brain labelled that of a “furiosus” by the judge at Tsafendas’s trial for the assassination of H. F. Verwoerd. The chapter discusses The Master Is Drowning and My Lovely Day, in part to consider the various iterations of “she” across the works but also the images of diving, swimming, and submergence as images of, in part, the artist herself as she dives into her wet mediums of ink and glue. In the films, the chapter argues, the analogue of the “painted line” is the subtitled narrative which is then shaken up or partially dissolved by the montages that flow beneath the words.
Impossible Form
Authors: Akomfrah John , Sedira Zineb , Siopis Penny
Published: June 2024

This is a three-way conversation between the filmmakers Penny Siopis, John Akomfrah, and Zenab Sedira that began in Beirut in 2015 and is taken up here as an extended exchange about conceptual overlaps in their work as well as processes of making film. Akomfrah describes Siopis’s filmmaking as exercises in impossible form, so intricate and opaque are the demarcations between the autobiographical, the fictional, fable, allegory, story, and document in her works. In the course of the conversation, Akomfrah, Sedira, and Siopis elaborate on and explore their own tentacular and labyrinthine processes of producing film, as they persuade radically different and dispersed images to “talk” to each other. How they work with and think about archives, collecting, and collage; what their views are on the essay film form and its legacies in the present; their uses of voice and sound; and their negotiation of digital and analog forms are all discussed here. Finally, water, spilling, and unfixity are explored, not least in the context of the emerging crises, including climate change, in the twenty-first century.
Identifying and Treating Those at Risk: Disparities in Rapid Relapse Among TNBC Patients in the National Cancer Database
Authors: Rahurkar Saurabh , Jonnalagadda Pallavi , Stover Daniel , Andersen Barbara , Handley Demond , Elsaid Mohamed I. , Chen J. C. , Obeng-Gyasi Samilia
Published: June 2024

Purpose

This study was designed to characterize features of rapid relapse TNBC (rrTNBC), an aggressive, poor prognosis breast cancer subset using the National Cancer Database (NCDB).

Methods

Patients diagnosed with TNBC between 2010 and 2019 within NCDB were included in analyses. rrTNBC was defined as all-cause mortality ≤24 months from diagnosis. Patient demographic, tumor, and treatment association with rrTNBC were evaluated in univariate, bivariate analyses, and multiple logistic regression models. Two-part models are used to compare receipt of treatment (i.e., receipt of both chemotherapy and breast surgery) versus not in its relationship with rrTNBC.

Results

Overall, 14.5% of patients were categorized as rrTNBC. Age older than 75 years (−41.3%), Black race (−1.4%), Medicare (−2.6%), and Charlson-Deyo score ≥2 (−4.9%) were associated with a lower probability of receiving both chemotherapy and breast surgery. Not receiving both treatments (vs. receiving both chemotherapy and breast surgery) was associated with a two-to-three-fold higher probability of rrTNBC among patients aged older than 75 years (16.6% vs. 6%), having Medicare (3.6% vs. 1.6%), and Charlson-Deyo score ≥2 (16.6% vs. 5.9%).

Conclusions

Age, insurance, and comorbidity were related to a lower likelihood of treatment; yet receiving treatment reduced the risk of rrTNBC threefold for each. These findings might be valuable to inform clinical care delivery, as well as future research that examines treatment protocols among diverse patients.
Climate politics in global Hobbesian Jungle
Authors: Feng Rui
Published: June 2024

Background Climate change, largely triggered by human-induced greenhouse gases (GHGs) emissions, seems unstoppable. There was a strong rebound of anthropogenic emissions of CO2, the preponderant GHG in terms of contribution to global warming, around the world after the COVID-19 lockdown. Also, there is still no widely accepted international treaty on curbing the anthropogenic emissions of CH4 and N2O, the second and third predominant GHG, respectively, so far. Thereby, prima facie, in respect to mitigating climate change, currently, humans have no aces up their sleeves. It seems that current temperature rise is not high enough to take alarm until the occurrence of tipping point. Policy Climate-related international treaties, such as 2016 Paris agreement, are compromises among conflicting geopolitical pressures. However, currently, the climate treaties show little mandatory binding force on the signatories who are able to violate and then get off scot-free, thus may end up like a nostrum. Throughout the European history, I find that the only way, if at all, to achieve the peace or obedience of a treaty is via balancing powers, embodied in Bismarck’s Realpolitik of Germany and Richelieu’s Raison d'état of France. Similarly, the Chinese history in East Asia proved the significance of unadulterated ideological neutrality and Darwinian adaptability in the kaleidoscope of evolving circumstances in maintaining order and enforcement of international treaties through balancing the power of rivalries to constrain ever-recurring challengers for equilibrium. Recommendations A successful policy needs to make a thorough analysis of all relevant factors to form a long-term strategic notion. Then, statesmen need to distill an array of nebulous, always contradictory options into a tenacious, controllable direction. Thereby, I suggest that, for better curbing global warming, climate agreements or climate club be incorporated into an overall geopolitical framework among the international communities.
sSNAPPY: an R/Bioconductor package for single-sample directional pathway perturbation analysis
Authors: Liu Wenjun , Mäkinen Ville-Petteri , Tilley Wayne D , Pederson Stephen M
Published: June 2024

A common outcome of analysing RNA-Seq data is the detection of biological pathways with significantly altered activity between the conditions under investigation. Whilst many strategies test for over-representation of genes, showing changed expression within pre-defined gene-sets, these analyses typically do not account for gene-gene interactions encoded by pathway topologies, and are not able to directly predict the directional change of pathway activity. To address these issues we have developed sSNAPPY,now available as an R/Bioconductor package, which leverages pathway topology information to compute pathway perturbation scores and predict the direction of change across a set of pathways. Here, we demonstrate the use of sSNAPPY by applying the method to public scRNA-seq data, derived from ovarian cancer patient tissues collected before and after chemotherapy. Not only were we able to predict the direction of pathway perturbations discussed in the original study, but sSNAPPY was also able to detect significant changes of other biological processes, yielding far greater insight into the response to treatment. sSNAPPY represents a novel pathway analysis strategy that takes into consideration pathway topology to predict impacted biology pathways, both within related samples and across treatment groups. In addition to not relying on differentially expressed genes, the method and associated R package offers important flexibility and provides powerful visualisation tools. R version: R version 4.3.3 (2024-02-29) Bioconductor version: 3.18 Package: 1.6.1
Understanding Syrian migration in Lebanon: a methodological framework
Authors: Trovato Maria Gabriella , Al-Akl Nayla , Ali Dana
Published: June 2024

Background Wars, crises, and climate change are just a few of the worldwide concerns that have resulted in the forced relocation of millions of people. After 12 years of conflict in Syria, millions of Syrians are still displaced in the neighbouring countries, and their conditions have worsened due to the economic and socio-political crisis of the region. This paper reports on a study conducted in Lebanon as part of the EU Horizon-funded project ADMIGOV – Advancing Alternative Migration Governance. It describes the methodological framework used to study Syrian migration in Lebanon and sheds light on the phenomenon's patterns, challenges, and impacts. Methods In our study, we opted for a mixed method. It is built on a large corpus of primary data collected over the course of years of intensive, in-depth fieldwork and the author's immersion in the community. Alongside observations, quantitative and qualitative phone interviews were conducted to obtain the perceptions of displaced Syrians living in informal tented settlements in rural Lebanon and an incomplete building in the city of Saida. This interview data is accompanied by primary and secondary data sources, including the findings of other European research projects, statistics from UNHCR and IOM, and academic and press articles. Results Our research revealed the difficulties Syrians displaced in Lebanon encounter while navigating the challenging situation they are trapped in. Based on a case study approach, it unveils similarities and differences determined by the government’s no encampment policy that led to self-settled practices across the country. This approach helped in understanding the challenging dynamic created by weak public institutions and their failure to guarantee the observance of basic human rights, compromising displaced Syrians safety. The weakness of public institutions and their failure to guarantee the observance of basic human rights has compromised displaced safety. Moreover, even though the development interventions and aid assistance have been necessary for Syrians' survival, they proved insufficient, and unequally distributed by location evidencing the inefficiencies of the majority of development aid projects. Conclusions The findings contribute to an enriched understanding of the situation of Syrians in Lebanon and offer insights for policymakers, practitioners, and researchers working in the field of forced migration and humanitarian responses.
Universal mental health training for frontline professionals: evaluation of pilot trial in Ukraine
Authors: Gorbunova Viktoriia , Klymchuk Vitalii , Portnytska Nataliia , Savychenko Olha , Tychyna Iryna , Steffgen Georges
Published: June 2024

Background Increasing accessibility of mental health services and expanding universal health coverage is possible worldwide by using a task-shifting approach as partial delegation of some mental health support tasks to trained non-mental health service providers in order to use the available workforce more efficiently. The Universal Mental Health Training (UMHT), which is dedicated to this aim, was developed and piloted in Ukraine. The UMHT is an educational program for frontline professionals on high-quality and evidence-based responses to the mental health needs of the population they serve. Methods The pilot trial of UMHTs’ effectiveness was conducted with 307 frontline professionals divided into 24 training groups. The control group included 211 persons with the same occupation background who participated in training later (waiting list). All the groups took part in eight-hour training, which includes one introductory module that introduces the mental health topic alongside a five-step model of UMHT, two disorders-focused modules with the steps adjusted to work with specific disorders, and the final module that considers possible difficulties frontline professionals might experience. Three effectiveness measurements were used in the outcome assessment: readiness to interact with people with mental health issues at work, mental health awareness and mental health proficiency. Results Analysis of the outcome data for the frontline professionals who underwent the UMHT revealed a moderate effect size related to the knowledge of mental health conditions, mental health awareness, and increasing the readiness to interact with people with mental health issues in comparison to the control group. Conclusions High-level utilisation of the UMHT at work by trained professionals confirms the effectiveness of the developed intervention. Obtained results favour the continuation of the development of the UMHT and future implementation research in this field in Ukraine and potentially in other low- and middle-income countries.
Investigating the causal effect of previously reported therapeutic agents for colorectal cancer prevention: protocol for a Mendelian randomization analysis
Authors: Fryer Ella , Martin Richard M. , Haycock Philip , Yarmolinsky James
Published: June 2024

Background Colorectal cancer (CRC) is the third most common cancer worldwide, with 1.9 million new cases in 2020 and a predicted rise to 3.2 million in 2040. Screening programmes are already in place to aid early detection and secondary prevention of CRC, but the rising prevalence means additional approaches are required in both primary and secondary prevention settings. Preventive therapy, whereby natural or synthetic agents are used to prevent, reverse or delay disease development, could be an effective strategy to further reduce cancer risk and potential agents have already been identified in conventional observational studies. However, as such studies are vulnerable to confounding and reverse causation, we aim to evaluate these observed relationships using Mendelian randomization (MR), an alternative causal inference approach which should be less susceptible to these biases. Methods and analysis We will use two-sample MR, which uses two independent samples for the exposure and outcome data, to investigate previously reported observational associations of multiple potential preventive agents with CRC risk. We define preventive agents as any synthetic (e.g. approved medication) or natural (e.g. micronutrient, endogenous hormone) molecule used to reduce the risk of cancer. We will first extract potential preventive agents that have been previously linked to CRC risk in observational studies from reviews of the literature. We will then evaluate whether we can develop a genetic instrument for each preventive agent from previously published genome-wide association studies (GWASs) of direct measures of molecular traits (e.g. circulating levels of protein drug targets, blood-based biomarkers of dietary vitamins). The summary statistics from these GWASs, and a large GWAS of CRC, will be used in two-sample MR analyses to investigate the causal effect of putative preventive therapy agents on CRC risk. Sensitivity analyses will be conducted to evaluate the robustness of findings to potential violations of MR assumptions.
The genome sequence of a cased caddisfly, Mystacides longicornis (Linnaeus, 1758)
Authors: Coleman Derek ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: June 2024

We present a genome assembly from an individual male Mystacides longicornis (cased caddisfly; Arthropoda; Insecta; Trichoptera; Leptoceridae). The genome sequence is 665.1 megabases in span. Most of the assembly is scaffolded into 20 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.75 kilobases in length.
Mortality, morbidity and educational outcomes in children of consanguineous parents in the Born in Bradford cohort
Authors: Small Neil , Kelly Brian , Malawsky Daniel S. , Lodh Rajib , Oddie Sam , Wright John
Published: June 2024

Background Children of consanguineous parents have a higher risk of infant and childhood mortality, morbidity and intellectual and developmental disability. Methods Using a prospective UK based longitudinal family cohort study we quantify differences according to the consanguinity status of children from birth to age 10 in mortality, health care usage, two health and three educational outcomes. Results Compared to children whose parents were not related children whose parents were first cousins were more likely to die by the age of 10 years (odds ratio 2.81, 95% CI 1.82-4.35) to have higher rates of primary care appointments (incident rate ratio 1.39, 95% CI 1.34-1.45) and more prescriptions (incident rate ratio 1.61, 95% CI 1.50-1.73). Rates of hospital accident and emergency attendance (incident rate ratio 1.21,95% CI 1.12-1.30) and hospital outpatients’ appointments (incident rate ratio 2.21,95% CI 1.90-2.56) are higher. Children whose parents are first cousins have higher rates of speech/ language development difficulties (odds ratio 1.63, 95% CI 1.36-1.96) and learning difficulties (odds ratio 1.89, 95% CI 1.28-2.81). When they begin school children whose parents are first cousins are less likely to reach phonics standards (odds ratio 0.73, 95% CI 0.63-0.84) and less likely to show a good level of development (odds ratio 0.61, 95% CI 0.54-0.68). At age 10 there are higher numbers with special educational needs who are from first cousin unions when compared to all children whose parents are not blood relations (odds ratio 1.38, 95% CI 1.20-1.58). Effect sizes for consanguinity status are similar in univariable and multivariable models where a range of control variables including deprivation are added. Conclusions There is higher childhood mortality and greater use of health care as well as higher rates of learning difficulties, speech and language development challenges and substantive differences in education outcomes in children whose parents are first cousins