bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using polygenic risk scores to investigate the evolution of smoking and mental health outcomes in UK biobank participants
Authors: Balbuena Lloyd , Peters Evyn , Speed Doug 
Published: August 2023

AbstractObjectiveMendelian randomization studies report a bi‐directional relation between cigarette smoking and mental disorders, yet from a clinical standpoint, mental disorders are the focus of treatment. Here, we used an event history framework to understand their evolution in the life course. Our objective was to estimate the relative contribution of genetic predispositions and self‐reported smoking status (never, former, and present smoker) to hospitalizations for major depression, bipolar disorder, and schizophrenia.MethodsWe calculated polygenic risk scores (PRS) for ever smoking, pack‐years of smoking as a proportion of adult life, and neuroticism in 337,140 UK Biobank participants of white British ancestry. These PRS and self‐reported smoking status were entered as explanatory variables in survival models for hospitalization.ResultsThe estimated single nucleotide polymorphisms heritabilities (h2) were 23%, 5.7%, and 5.7% for pack‐years, ever smoking, and neuroticism respectively. PRS pack‐years and PRS neuroticism were associated with higher hospitalization risk for mental disorders in all smoking status groups. The hazard for mental health hospitalization was higher in both previous (HR: 1.50, CI: 1.35–1.67) and current (HR: 3.58, 2.97–4.31) compared to never smokers, after adjusting for confounders.ConclusionSince genetic liabilities for smoking and neuroticism are fixed at conception and smoking initiation generally started before age 20, our results show that preventing smoking in adolescents probably prevents the development of mental disorders.
Addressing the GP vocational training crisis in remote Australia: Lessons from the Northern Territory
Authors: Russell Deborah Jane , Monani Devaki , Martin Priya , Wakerman John 
Published: August 2023

AbstractObjectiveGP vocational training enrolments are declining Australia‐wide and, in the Northern Territory (NT), considered by some as ‘…the litmus test for the national scene’ the decline is precipitous. This research investigates the drivers of declining GP training uptake in the NT and identifies and ranks potential solutions.SettingNT, Australia.ParticipantsTen senior medical students, 6 junior doctors, 11 GP registrars, 11 GP supervisors and 31 stakeholders.DesignMixed methods: scoping review of Australian literature mapping key concepts to GP training pathway stages and marketing/communications; secondary data analyses; key informant interviews; and a stakeholder validation/prioritisation workshop. Interview data were thematically analysed. Workshop participants received summarised study findings and participated in structured discussions of potential solutions prior to nominating top five strategies in each of five categories.ResultsHighly prioritised strategies included increasing prevocational training opportunities in primary care and selecting junior doctors interested in rural generalism and long‐term NT practice. Also ranked highly were: [Medical School] ensuring adequate infrastructure; [Vocational Training] offering high quality, culturally sensitive, flexible professional and personal support; [General Practice] better remunerating GPs; and [Marketing] ensuring positive aspects such as diversity of experiences and expedited GP career opportunities were promoted.ConclusionMultifaceted strategies to increase GP training uptake are needed, which target different stages of GP training. Effective action is likely to require multiple strategies with coordinated action by different jurisdictional and national key stakeholder agencies. Foremost amongst the interventions required is the urgent need to expand primary care training opportunities in NT for prevocational doctors.
Expanding identity beyond the human
Authors: Mehl‐Madrona Lewis 
Published: August 2023

AbstractEcofeminists, environmental activists, and ecologists are calling humans to change our relationships to other‐than‐humans and more‐than‐humans. Indigenous people and knowledge systems are often exemplified as ways for non‐Indigenous people to relate to these entities. While Indigenous people have historically participated in epistemologies and modes of perception that rendered them more able to connect to non‐humans, these relationships have not always been peaceful or mutually advantageous. Examples are cited in which annihilating all beavers was the goal, and the fur trade is cited as a time when Indigenous people in North America gained mastery over animals that had previously threatened them, leading to near extinction for some species in some locations over a short time. Bear–human marriage stories provide us with another way to view the human–animal relationship, which is sometimes violent. Through multiple conversations with Elders over time, I have been accumulating a sense of Indigenous North American (INA) theories of mind, self, and consciousness. I apply the results of my discussions to the question of whether we are creating a new consciousness of relations with non‐humans that has not previously existed in INA thought, though it has its progenitors. I also apply insights from recent literature on psychedelics. This new thought arises from the current domination of the planet and animals by human beings and the relative lack of threat to humans from animals. Indeed, we are more dangerous to them than they are to us. Within this context, we can construct a new consciousness of non‐humans, which has its historical antecedents and which is also entirely new.
Review article: Externally derived control arms—An opportunity for clinical trials in inflammatory bowel disease?
Authors: Honap Sailish , Peyrin‐Biroulet Laurent 
Published: August 2023

SummaryBackgroundOne of the greatest challenges in the current IBD clinical trial landscape is, perhaps, the recruitment and retention of eligible participants. Seamless testing of promising investigational compounds is paramount to address unmet needs, but this is hindered by a number of barriers, particularly patient concerns of placebo assignment.AimsTo review the use of novel trial designs leveraging externally derived data to synthetically create control groups or augment existing ones, and to summarise the regulatory position on the use of external controls for market authorisation.MethodsWe conducted a PubMed literature search without restriction using search terms such as ‘external controls’ and ‘historical controls’ to identify relevant articles.ResultsExternal controls are increasingly being used outside the context of cancer and rare diseases, including IBD, and increasingly recognised by regulatory bodies. Such designs, particularly in earlier phase trials, can inform key nodes in drug development and permit evaluating efficacy of interventions without combating the ethical and numerical enrolment challenges described. However, the lack of randomisation and blinding subjects them to significant bias. Groups require robust statistical and computational approaches to ensure patient‐level data across groups are adequately balanced.ConclusionsWhile this approach has several pitfalls, and is not robust enough to replace traditional randomised, placebo‐controlled trials, it may offer a compromise to address key research questions at a more rapid pace, with fewer patients, and lower cost.
In search of change: Organizational role expectancies of CSR professionals
Authors: Pollach Irene , Thomsen Christa , Nielsen Anne Ellerup 
Published: August 2023

AbstractBased on an integrative discourse methodology, this study examines the organizational role expectancies of CSR professionals as articulated in CSR job advertisements, focusing specifically on what organizations expect CSR professionals to change. Four types of change were identified and organized into a matrix based on the inside or outside stimuli for these changes and their expected effects, which can materialize inside or outside the organization. Specifically, the four types of change include organizational development (aligning practices with organizational values), compliance (aligning practices with external norms), social approval (changing public perceptions), and agenda setting (changing the environment). These four types of change highlight the transformative as well as the self‐serving nature of the changes organizations expect CSR professionals to accomplish. On the practical side, the types of change provide insights into CSR as an occupation, as they highlight desired skills and competences of CSR professionals.
Versius robotic surgical system: case series of 18 robot‐assisted radical prostatectomies
Authors: De Maria Maurizio , Meneghetti Iacopo , Mosillo Luca , Collins Justin W. , Catalano Chiara 
Published: August 2023

ObjectiveTo present the results of the first series of patients treated with robot‐assisted radical prostatectomy (RARP) with the use of the Versius® Surgical System (CMR Surgical Ltd., Cambridge, UK). RARP has demonstrated better perioperative outcomes compared to open RP. However, RARP remains limited by platform availability and cost‐effectiveness issues. The increasing competition from new robotic surgical platforms may further drive utilisation of the robotic approach.Patients and MethodsData were collected prospectively for our first 18 consecutive patients with localised prostate cancer who underwent RARP at our centre over a 3‐month period. We recorded parameters, including patient demographics and perioperative outcomes. We also report our optimised set‐up with regard to trocar placement, bedside unit placement, and overall composition of the operating room for this procedure. Describing the incremental modifications carried out to achieve reductions in set‐up and operating times to optimise utilisation of the Versius system.ResultsThe median (interquartile range [IQR]) set‐up time was 8.5 (7–10) min. The median (IQR) console time was 201 (170–242) min. The median (IQR) operative time was 213 (186–266) min. The median (IQR) total surgery time was 226 (201–277) min. Bilateral pelvic lymphadenectomy median (IQR) time was 19 (17–20) min. There were no complications and/or limitations related to the use of the Versius system including need for conversion. There were no relevant intra‐ or postoperative complications at the 1‐month follow‐up related to the use of the Versius system. Patients were discharged after a median (IQR) of 4 (3.75–5) days, and the transurethral catheter was removed after a mean (range) of 8 (7–14) days. Continence at 2 months was achieved in 72.2% of the patients.ConclusionsPerforming RARP using the Versius system is feasible, safe, and easily reproducible. Our set‐up enables a rapid docking approach and efficient completion of the surgery.
Graph‐Based Synthesis for Skin Micro Wrinkles
Authors: Weiss S. , Moulin J. , Chandran P. , Zoss G. , Gotardo P. , Bradley D. 
Published: August 2023

AbstractWe present a novel graph‐based simulation approach for generating micro wrinkle geometry on human skin, which can easily scale up to the micro‐meter range and millions of wrinkles. The simulation first samples pores on the skin and treats them as nodes in a graph. These nodes are then connected and the resulting edges become candidate wrinkles. An iterative optimization inspired by pedestrian trail formation is then used to assign weights to those edges, i.e., to carve out the wrinkles. Finally, we convert the graph to a detailed skin displacement map using novel shape functions implemented in graphics shaders. Our simulation and displacement map creation steps expose fine controls over the appearance at real‐time framerates suitable for interactive exploration and design. We demonstrate the effectiveness of the generated wrinkles by enhancing state‐of‐art 3D reconstructions of real human subjects with simulated micro wrinkles, and furthermore propose an artist‐driven design flow for adding micro wrinkles to fictional characters.
The impact of a dedicated operating room team on robotic transplant program growth and fellowship training
Authors: Hill Angela L. , Scherer Meranda D. , Kiani Amen , Vachharajani Neeta , Matson Sarah , Cullinan Darren R. , Martens Greg R. , Yu Jennifer , Davidson Jesse T. , Wellen Jason R. , Chapman William C. , Doyle Majella B. , Khan Adeel S. 
Published: August 2023

AbstractIntroductionDespite considerable interest in robotic surgery, successful incorporation of robotics into transplant programs has been challenging. Lack of a dedicated OR team with expertise in both robotics and transplant is felt to be a major barrier. This paper assesses the impact of a dedicated robotic transplant team (DART) on program growth and fellowship training at one of the largest robotic transplant programs in North America.MethodsThis is a single center, retrospective review of all robotic operations performed on the transplant surgery service from October 2017 to October 2022. DART was incorporated in February 2020 and included transplant first assists (RFAs), scrub technologists and circulating nurses who received robotic training. Robotic experience before and after DART was compared to assess its impact on program growth and training.ResultsFour hundred and two robotic cases were performed by five transplant surgeons: 63 pre‐DART and 339 post‐DART. 40% of cases were transplant‐related and 59.5%, HPB. There was a significant increase in case volume (2.5–10.6 cases/month, p < .0001) and complexity (36.5% vs. 70.3% high complexity cases, p < .0001) post‐DART. RFA case coverage increased from 17% to 95%, and participation of transplant fellows as primary surgeons increased from 17% to 95% post‐DART period (both p < .05). Conversion rates (9.5% vs. 4.1%) and room turn‐around‐times (TAT) (58.4 vs. 40.3 min) were lower post‐DART (p < .05). There were no emergent conversions, conversions in transplant patients, or robot‐related complications in either group.ConclusionOR teams with expertise in robotics and transplant surgery can accelerate growth of robotic transplant programs while maintaining patient safety.
A randomized, placebo‐controlled study to evaluate safety and pharmacokinetics of ART‐001 with a novel oral pediatric formulation in healthy subjects
Authors: Tanaka Akira , Uemura Naoto , Kuniyeda Kanako , Ando Haruhi , Higashi Toshinori , Nagabukuro Hiroshi 
Published: August 2023

AbstractART‐001 is an orally available selective PI3Kα inhibitor currently being developed for the treatment of slow‐flow vascular malformations (SFVMs). ART‐001 used to be developed for advanced solid tumors, but was suspended largely due to significant pharmacokinetic (PK) variability in its phase I studies. This phase I, randomized, double‐blinded, placebo‐controlled study evaluated safety, tolerability and PK of ART‐001 with a newly developed dry syrup formulation, which was designed to optimize PK properties of ART‐001 and to be compliant with the pediatric population. Single and multiple doses of ART‐001 were administered to healthy male adults. ART‐001 was rapidly absorbed after the single and repeated doses, and the exposure of ART‐001 increased with increased dose. The dry syrup formulation substantially improved the intersubject PK variability. Food decreased area under the concentration‐time curve (AUC) and maximum plasma concentration by 12% and 36%, respectively. The plasma concentration had reached a steady‐state on day 5 of the repeated doses of 100 mg and AUC accumulation ratio was 1.9. There were no deaths or serious adverse events. The most frequent adverse event was hyperglycemia. All cases of hyperglycemia were mild to moderate and transient, and required no medical interventions. Serum creatinine increase was observed in 300 mg once daily dosing group leading to dose discontinuation on day 5. In conclusion, it was demonstrated that the single doses and repeated doses of the ART‐001 dry syrup formulation, at up to 400 and 100 mg, respectively, were safe and tolerated with favorable PK profile, supporting further clinical development for the treatment of SFVMs.
Pancreatic panniculitis revisited: A series of 34 patients
Authors: Seguí Mireia , Rodríguez‐Jiménez Pedro , Fraga Javier , Navas José , Ríos Juan José , Revilla David , Santos‐Briz Ángel , Lluch Juan José , Fernández Figueras María Teresa , Luque Mar , Llamas Velasco Mar 
Published: August 2023

AbstractBackgroundPancreatic panniculitis is a rare form of panniculitis generally associated with acute or chronic pancreatitis, and less frequently with pancreatic carcinoma. Clinically, it presents with subcutaneous nodules usually located in the lower extremities, however, it presents an almost pathognomonic histopathological finding with enzymatic fat necrosis in the adipose tissue.MethodsIn this retrospective case series of five hospitals, biopsy specimens of cutaneous lesions of pancreatic panniculitis were reviewed. Clinical information was obtained through medical records.ResultsA total of 34 cases were included, 23 women and 11 men, aged between 31 and 92 years. The most common associated pancreatic disease was acute pancreatitis (23 cases) and its main triggering cause was gallstones (17 cases). In two patients it was related to chronic pancreatitis and six cases were associated with malignancy. Histopathological findings were always the key to diagnosis. In the biopsies reviewed, mostly lobular panniculitis with the characteristic necrosis of the adipocytes was observed. In addition, nine of the cases presented with Splendore–Hoeppli phenomenon.ConclusionsWe present the largest series of pancreatic panniculitis. Clinically, the female predominance and biliary lithiasis as the main cause of acute pancreatitis are to be emphasized. Histopathologically, a peripheral eosinophilic striated rim surrounding aggregates of ghost adipocytes consistent with Splendore–Hoeppli is an additional clue to its diagnosis.
NONO::TFE3 fusion cutaneous epithelioid and spindle cell tumor: A case series
Authors: See Sharlene Helene C. , Olivares Shantel , Kulkarni Maansi , Dhillon Soneet K. , Fumero‐Velazquez Monica Stella , Hagstrom Michael Norman E. , Gerami Pedram 
Published: August 2023

AbstractThe NONO::TFE3 fusion has been described in MiT family translocation renal cell carcinomas as well as extracutaneous perivascular epithelioid cell tumors (PEComas). PEComas are known to express myogenic and melanocytic markers but SOX10 and p63 positivity has never been reported. We report two primary cutaneous tumors that morphologically and molecularly fit PEComas, both harboring the NONO::TFE3 fusion, but with an unusual immunophenotype of SOX10 and p63 positivity. One case was on an 80‐year‐old male's finger, and the other one was on a 72‐year‐old female's thigh. Both were well‐circumscribed multinodular dermal tumors composed of nests of monotonous epithelioid to spindled cells with pale to vacuolated cytoplasm, some of which were arranged around blood vessels. Both tumors were positive for SOX10, S100, and p63, focally positive for Melan‐A, and negative for myogenic markers. There are very little data regarding the molecular findings of primary cutaneous PEComas. While the NONO::TFE3 fusion has been identified in extracutaneous PEComas, it has never been reported in primary cutaneous cases. We believe these cases represent a previously undescribed subtype of cutaneous tumor which shows some immunophenotypic expression of melanocytic markers and we named these cases NONO::TFE3 fusion cutaneous epithelioid and spindle cell tumor. Further, we raise the question of whether this tumor should fall under the rubric of PEComa because of its morphology, partial expression of melanocytic markers, and the presence of the NONO::TFE3 fusion, or whether these tumors represent a separate novel class of tumors since the immunophenotypic expression of SOX10 and p63 is unusual for PEComas.
Single closed‐loop acoustic stimulation targeting memory consolidation suppressed hippocampal ripple and thalamo‐cortical spindle activity in mice
Authors: Aksamaz Sonat , Mölle Matthias , Akinola Esther Olubukola , Gromodka Erik , Bazhenov Maxim , Marshall Lisa 
Published: August 2023

AbstractBrain rhythms of sleep reflect neuronal activity underlying sleep‐associated memory consolidation. The modulation of brain rhythms, such as the sleep slow oscillation (SO), is used both to investigate neurophysiological mechanisms as well as to measure the impact of sleep on presumed functional correlates. Previously, closed‐loop acoustic stimulation in humans targeted to the SO Up‐state successfully enhanced the slow oscillation rhythm and phase‐dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation‐induced hippocampo‐thalamo‐cortical activity and retention performance on a hippocampus‐dependent object‐place recognition task in mice by applying acoustic stimulation at four estimated SO phases compared to sham condition. Across the 3‐h retention interval at the beginning of the light phase closed‐loop stimulation failed to improve retention significantly over sham. However, retention during SO Up‐state stimulation was significantly higher than for another SO phase. At all SO phases, acoustic stimulation was accompanied by a sharp increase in ripple activity followed by about a second‐long suppression of hippocampal sharp wave ripple and longer maintained suppression of thalamo‐cortical spindle activity. Importantly, dynamics of SO‐coupled hippocampal ripple activity distinguished SOUp‐state stimulation. Non‐rapid eye movement (NREM) sleep was not impacted by stimulation, yet preREM sleep duration was effected. Results reveal the complex effect of stimulation on the brain dynamics and support the use of closed‐loop acoustic stimulation in mice to investigate the inter‐regional mechanisms underlying memory consolidation.
More (corrective) consecutive saccades after a lesion to the posterior parietal cortex
Authors: Böing Sanne , Fabius Jasper H. , Hakkenberg Marjoleine , Nijboer Tanja C. W. , Van der Stigchel Stefan 
Published: August 2023

AbstractTo reach a target, primary saccades (S1s) are often followed by (corrective) consecutive saccades (S2, and potentially S3, S4, S5), which are based on retinal and extraretinal feedback. Processing these extraretinal signals was found to be significantly impaired by lesions to the posterior parietal cortex (PPC). Recent studies, however, added a more nuanced view to the role of the PPC, where patients with PPC lesions still used extraretinal signals for S2s and perceptual judgements (Fabius et al., 2020; Rath‐Wilson & Guitton, 2015). Hence, it seems that a PPC lesion is not disrupting extraretinal processing per se. Yet, a lesion might still result in less reliable processing of extraretinal signals. Here, we investigated whether this lower reliability manifests as decreased or delayed S2 initiation. Patients with PPC lesions (n = 7) and controls (n = 26) performed a prosaccade task where the target either remained visible or was removed after S1 onset. When S1 is removed, accurate S2s (corrections of S1 error) rely solely on extraretinal signals. We analysed S2 quantity and timing using linear mixed‐effects modelling and additive hazards analyses. Patients demonstrated slower S1 execution and lower S1 amplitudes than controls, but their S2s still compensated the S1 undershoot, also when they only relied on extraretinal information. Surprisingly, patients showed an increased amount of S2s. This deviation from control behaviour can be seen as suboptimal, but given the decreased accuracy of the primary saccade, it could be optimal for patients to employ more (corrective) consecutive saccades to overcome this inaccuracy.