bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic microbial consortia for the treatment of Clostridioides difficile infection in mice model
Authors: Liu Jinqiu , Zhu Wei , Lessing Duncan James , Chu Weihua
Published: August 2023

Clostridioides difficile infection (CDI) as of recent has become a great concern to the impact on human health due to its high hazardous risk and rate of recurrence. Live bacterial therapeutics is a promising method to treat or prevent CDI. Here, a synthetic microbial consortia (SMC) B10 was constructed using probiotic strains with antibacterial and anti‐quorum sensing activities, and the therapeutic effect of SMC B10 against C. difficile infection was evaluated in vitro. Compared to the model group, the treatment of SMC B10 significantly increased the survival rate. The clinical signs of mice were significantly ameliorated, especially the cecum injury, while the secretion of pro‐inflammatory associated cytokines such as IL‐1α, IL‐6, IL‐17A and TNF‐α was reduced, the expression of TLR4 was inhibited, which alleviated the inflammatory response, and the expression of the tight junction protein Claudin‐1 was increased, ultimately promoting the recovery of host health. The treatment of B10 restored gut microbiota dysbiosis and led to a healthy intestinal microbiota structure, significantly improved alpha diversity, suppressing potentially harmful bacteria and restoring other core bacterial species. In conclusion, SMC B10 can effectively treat CDI through modulate gut microbiota and attenuate the inflammatory response.
Recurrent hemichorea in an adolescent with systemic lupus erythematosus and previous ipsilateral cerebral infarction
Authors: Yu Ya‐Wen , Chung Cheng‐Yu , Chiou Yee‐Hsuan , Fang Nai‐Wen
Published: August 2023

Systemic lupus erythematosus (SLE) can present with movement disorders, among which chorea is closely associated with antiphospholipid (aPL) antibodies. Brain imaging results obtained in patients with chorea are generally inconsistent with the clinical manifestation of chorea; moreover, medical tests for hemichorea, which are expected to reveal distinct localization, may show negative findings. Herein, we present a case of a 15‐year‐old girl with SLE who had a history of left cerebral infarction; tests revealed elevated aPL levels, and she developed recurrent left hemichorea 2 years later. Brain magnetic resonance imaging (MRI) results revealed no acute lesions during each episode of involuntary movements, and an MRI perfusion scan failed to provide an explanation for the asymmetric presentation. Although various hypotheses have been proposed regarding the mechanism underlying the occurrence of chorea, some scenarios still remain unexplained. Further investigation on the pathophysiology of chorea in SLE may be warranted to clarify its prognosis.
Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets
Authors: Dang Kai , Zhang Nan , Gao Haiqi , Wang Guifa , Liang Hui , Xue Meilan
Published: August 2023

Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short‐chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.
Health systems appraisal of the response to antimicrobial resistance in low‐ and middle‐income countries in relation to COVID‐19: Application of the WHO building blocks
Authors: Patel Jay , Fernandes Genevie , Mwamelo Ambele Judith , Sridhar Devi
Published: August 2023

COVID‐19 has inflicted both beneficial and damaging effects on health systems responding to antimicrobial resistance (AMR). Data shows that the positive impacts of the pandemic (including enhanced hygiene, mask wearing and widespread use of personal protective equipment), are likely to have been overshadowed by the negative effects: emerging AMR pathogens and mechanisms; further outbreaks and geographic spread of AMR to non‐endemic countries; rising infections from multidrug‐resistant pathogen; an overall higher burden of AMR. The multisectoral complexities of AMR and the totality of health systems challenge our ability to understand the impact of the COVID‐19 pandemic on country responses to AMR. In this analysis, we synthesise international evidence characterising the role of the pandemic on the six key building blocks of health systems in responding to AMR across low‐ and middle‐income countries (LMICs). We apply systems thinking within and between the building blocks to contextualise the impact of one pandemic on another.
AMPAR receptor inhibitors suppress proliferation of human small cell lung cancer cell lines
Authors: Masumoto Nami , Kato Shingo , Aichi Masahiro , Hasegawa Sho , Sahara Kota , Suyama Kumiko , Sano Akane , Miyazaki Tomoyuki , Okudela Koji , Kaneko Takeshi , Takahashi Takuya
Published: August 2023

Background

Small cell lung cancer (SCLC) is a neuroendocrine tumor with poor prognosis. Neuroendocrine tumors possess characteristics of both nerve cells and hormone‐secreting cells; therefore, targeting the neuronal properties of these tumors may lead to the development of new therapeutic options. Among the endogenous signaling pathways in the nervous system, targeting the glutamate pathway may be a useful strategy for glioblastoma treatment. Perampanel, an antagonist of the synaptic glutamate α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptor (AMPAR), has been reported to be effective in patients with glioblastoma. In this study, we aimed to investigate the antitumor effects of AMPAR antagonists in human SCLC cell lines.

Methods

We performed to examine the expression of AMPAR using Western blot and immunohistochemical analysis. The antitumor effects of AMPAR antagonists on human SCLC cell lines were investigated in vitro and in vivo. We also analyzed the signaling pathway of AMPAR antagonists in SCLC cell lines. Statistical analysis was performed by the GraphPad Prism 6 software.

Results

We first examined the expression of endogenous AMPAR in six human SCLC cell lines, detecting AMPAR proteins in all of them. Next, we tested the anti−proliferative effect of two AMPAR antagonists, talampanel and cyanquixaline, using SCLC cells in vitro and in vivo. Both AMPAR antagonists inhibited cell proliferation and mitogen‐activated protein kinase (MAPK) phosphorylation in SCLC cells in vitro. Further, we observed reduced proliferation of implanted cell lines in an in vivo setting, assessed by Ki‐67 immunohistochemistry. Additionally, using immunohistochemical analysis we confirmed AMPAR protein expression in human SCLC samples.

Conclusion

AMPAR may be a potential therapeutic target for SCLC.
Inferring time of infection from field data using dynamic models of antibody decay
Authors: Borremans Benny , Mummah Riley O. , Guglielmino Angela H. , Galloway Renee L. , Hens Niel , Prager K. C. , Lloyd‐Smith James O.
Published: August 2023

Studies of infectious disease ecology would benefit greatly from knowing when individuals were infected, but estimating this time of infection can be challenging, especially in wildlife. Time of infection can be estimated from various types of data, with antibody‐level data being one of the most promising sources of information. The use of antibody levels to back‐calculate infection time requires the development of a host‐pathogen system‐specific model of antibody dynamics, and a leading challenge in such quantitative serology approaches is how to model antibody dynamics in the absence of experimental infection data.

We present a way to model antibody dynamics in a Bayesian framework that facilitates the incorporation of all available information about potential infection times and apply the model to estimate infection times of Channel Island foxes infected withLeptospira interrogans.

Using simulated data, we show that the approach works well across a broad range of parameter settings and can lead to major improvements in infection time estimates that depend on system characteristics such as antibody decay rate and variation in peak antibody levels after exposure. When applied to field data we saw reductions up to 83% in the window of possible infection times.

The method substantially simplifies the challenge of modelling antibody dynamics in the absence of individuals with known infection times, opens up new opportunities in wildlife disease ecology and can even be applied to cross‐sectional data once the model is trained.
Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians
Authors: Zhu Yizhou , Ryu Seungjin , Tare Archana , Barzilai Nir , Atzmon Gil , Suh Yousin
Published: August 2023

Genome‐wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age‐related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non‐risk genotypes are linked to two distinct low‐frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age‐related diseases in the 9p21.3 locus.
Cooperative effects of SIRT1 and SIRT2 on APP acetylation
Authors: Li Na , Bai Ning , Zhao Xiong , Cheng Rong , Wu Xuan , Jiang Bo , Li Xiaoman , Xue Mingli , Xu Hongde , Guo Qiqiang , Guo Wendong , Ma Mengtao , Cao Sunrun , Feng Yanling , Song Xiaoyu , Wang Zhuo , Zhang Xiaoyu , Zou Yu , Wang Difei , Liu Hua , Cao Liu
Published: August 2023

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by amyloid‐β (Aβ) deposition and neurofibrillary tangles. Although the NAD+‐dependent deacetylases SIRT1 and SIRT2 play pivotal roles in age‐related diseases, their cooperative effects in AD have not yet been elucidated. Here, we report that the SIRT2:SIRT1 ratio is elevated in the brains of aging mice and in the AD mouse models. In HT22 mouse hippocampal neuronal cells, Aβ challenge correlates with decreased SIRT1 expression, while SIRT2 expression is increased. Overexpression of SIRT1 prevents Aβ‐induced neurotoxicity. We find that SIRT1 impedes SIRT2‐mediated APP deacetylation by inhibiting the binding of SIRT2 to APP. Deletion of SIRT1 reduces APP recycling back to the cell surface and promotes APP transiting toward the endosome, thus contributing to the amyloidogenic processing of APP. Our findings define a mechanism for neuroprotection by SIRT1 through suppression of SIRT2 deacetylation, and provide a promising avenue for therapeutic intervention of AD.
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

Objective

Mendelian 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.

Methods

We 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.

Results

The 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.

Conclusion

Since 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

Objective

GP 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.

Setting

NT, Australia.

Participants

Ten senior medical students, 6 junior doctors, 11 GP registrars, 11 GP supervisors and 31 stakeholders.

Design

Mixed 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.

Results

Highly 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.

Conclusion

Multifaceted 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

Ecofeminists, 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

Background

One 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.

Aims

To 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.

Methods

We conducted a PubMed literature search without restriction using search terms such as ‘external controls’ and ‘historical controls’ to identify relevant articles.

Results

External 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.

Conclusions

While 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

Based 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

Objective

To 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 Methods

Data 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.

Results

The 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.

Conclusions

Performing 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

We 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

Introduction

Despite 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.

Methods

This 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.

Results

Four 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.

Conclusion

OR 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

ART‐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

Background

Pancreatic 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.

Methods

In this retrospective case series of five hospitals, biopsy specimens of cutaneous lesions of pancreatic panniculitis were reviewed. Clinical information was obtained through medical records.

Results

A 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.

Conclusions

We 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

The 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

Brain 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

To 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.
Sartre and Frankfurt: Bad faith as evidence for three levels of volitional consciousness
Authors: Davenport John J.
Published: August 2023

This essay argues for a new conception of bad faith based partly on Harry Frankfurt's famous account of personal autonomy in terms of higher‐order volitions and caring, and based partly on Sartre's insights concerning tacit or pre‐thetic attitudes and “transcendent” freedom. Although Sartre and Frankfurt have rarely been connected, Frankfurt's concepts of volitional “wantonness” and “bullshit” (wantonness about truth) are similar in certain revealing respects to Sartre's account of bad faith. However, Sartre leaves no room for Frankfurt's central point that people can volitionally commit themselves to develop certain motives and reduce others, thereby shaping an authentic identity through volitional “identification” and “alienation” of motives. Frankfurt in turn minimizes the role that a sense of liberty to form and alter higher‐order volitions plays in experiences of autonomy, which Sartre recognizes in the transcendence of the “for‐itself.” When these points are combined, we get a tri‐level theory of intrasubjective volitional stances that explains Sartre's cases better than his own theory can, and also clarifies how sincere or procedurally autonomous self‐relation is possible.
Spatial heterogeneity of biomass turnover has contrasting effects on synchrony and stability in trophic metacommunities
Authors: Quévreux Pierre , Haegeman Bart , Loreau Michel
Published: August 2023

Spatial heterogeneity is a fundamental feature of ecosystems, and ecologists have identified it as a factor promoting the stability of population dynamics. In particular, differences in interaction strengths and resource supply between patches generate an asymmetry of biomass turnover with a fast and a slow patch coupled by a mobile predator. Here, we demonstrate that asymmetry leads to opposite stability patterns in metacommunities receiving localized perturbations depending on the characteristics of the perturbed patch. Perturbing prey in the fast patch synchronizes the dynamics of prey biomass between the two patches and destabilizes predator dynamics by increasing the predator's temporal variability. Conversely, perturbing prey in the slow patch decreases the synchrony of the prey's dynamics and stabilizes predator dynamics. Our results have implications for conservation ecology and suggest reinforcing protection policies in fast patches to dampen the effects of perturbations and promote the stability of population dynamics at the regional scale.
The role of neuronal antibodies in cryptogenic new onset refractory status epilepticus
Authors: Eisele Amanda , Schwager Matthias , Bögli Stefan Yu , Reichen Ina , Dargvainiene Justina , Wandinger Klaus‐Peter , Imbach Lukas , Haeberlin Marcellina , Keller Emanuela , Jelcic Ilijas , Galovic Marian , Brandi Giovanna
Published: August 2023

Most cases with new onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic workup. The aim of this study was to analyze the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic, and outcome parameters were characterized. We performed post hoc screening for known or potentially novel autoantibodies including immunohistochemistry (IHC) on rat brain with cerebrospinal fluid (CSF) and serum samples of cNORSE. Twenty patients with NORSE were identified. Etiologies included infections (n = 4), Creutzfeldt–Jakob disease (n = 1), CASPR2 autoimmune encephalitis (n = 1), and carotid artery stenosis with recurrent perfusion deficit (n = 1). Thirteen cases (65%) were cryptogenic despite detailed evaluation. A posteriori IHC for neuronal autoantibodies yielded negative results in all available serum (n = 11) and CSF (n = 9) samples of cNORSE. Our results suggest that neuronal antibodies are unlikely to play a major role in the pathogenesis of cNORSE. Future studies should rather focus on other—especially T‐cell‐ and cytokine‐mediated—mechanisms of autoinflammation in this devastating disease, which is far too poorly understood so far.
Genome‐wide diversity evaluation and core germplasm extraction in ex situ conservation: A case of golden Camellia tunghinensis
Authors: Zhu Xianliang , Zou Rong , Qin Huizhen , Chai Shengfeng , Tang Jianmin , Li Yingying , Wei Xiao
Published: August 2023

Whether ex situ populations constructed in the limited nursery resources of botanical gardens can preserve enough genetic diversity of endangered plants in the wild remains uncertain. Here, a case study was conducted with Camellia tunghinensis, which is one of the species with the lowest natural distribution area in the sect. Chrysantha (golden camellia) of the family Theaceae. We investigated the genetic diversity and population structure of 229 samples from wild and ex situ populations using genotyping by sequencing (GBS). Core germplasm was constructed from these samples. The results showed that wild C. tunghinensis exhibited high genetic diversity, with observed heterozygosity of 0.257–0.293 and expected heterozygosity of 0.247–0.262. Compared with wild populations, the genetic diversity of ex situ populations established by transplanting wild seedlings was close to or even higher. However, the genetic diversity of those established by seed or cuttings of a few superior trees was lower. The Admixture analysis revealed that the structure of the ex situ populations derived from seeds and cuttings was relatively simple compared with the ex situ populations derived from transplanted wild seedlings and wild populations. These results suggested that direct transplanting of wild seedlings was more conducive to preserving the genetic diversity of endangered plants in the wild. In addition, wild populations demonstrated a small differentiation (mean FST = 0.044) among themselves, possibly due to long‐term and frequent gene flow between the wild populations. In contrast, moderate differentiation (mean FST > 0.05) was detected among ex situ populations and between ex situ and wild populations. This may be the combined result of the absence of gene flow pathways and strong selection pressure in various ex situ environments. Finally, 77 core germplasms were extracted from 229, likely representing the genetic diversity of C. tunghinensis. This study provides future strategies for the ex situ conservation and management of the golden camellia species and other rare and endangered plants.
The relatives of people with depression: A systematic review and methodological critique of qualitative studies
Authors: Buus Niels , Petersen Alan , McPherson Susan , Meadows Graham , Brand Gabrielle , Ong Ben
Published: August 2023

Being a close relative of a person with depression can take a heavy toll on the former, but these relatives are increasingly made responsible for taking on extensive carer roles. Research on relatives of people with depression is currently dominated by a focus on “carer burden” and although such a focus can explain many relatives' experiences and daily lives, it provides very limited insight into the everyday life of a person living with someone with depression. Therefore, we scoped qualitative research on people who are relatives of people living with depression and identified knowledge gaps caused by explicit or implicit theoretical or methodological assumptions. We conducted an exhaustive literature search in CINAHL, PubMed, PsycINFO, Sociological Abstracts, and Eric. In total, 34 publications were included, their quality evaluated and their findings mapped and summarized. We identified four interrelated and overlapping themes that dominated the findings of the publications: (a) recognition of “depression”, (b) emotional responses, (c) interruptions of relationships, and (d) a staged psychosocial process. The vast majority of studies presented de‐contextualized and underinterpreted analyses assuming a homogeneity of (illness) experiences and disregarded the important influence of social contributors to social relationships, connectedness, and mental health problems.
Comparison of carbon and nitrogen accumulation rate between bog and fen phases in a pristine peatland with the fen‐bog transition
Authors: Yang Qiannan , Liu Ziping , Bai Edith
Published: August 2023

Long‐term carbon and nitrogen dynamics in peatlands are affected by both vegetation production and decomposition processes. Here, we examined the carbon accumulation rate (CAR), nitrogen accumulation rate (NAR) and δ13C, δ15N of plant residuals in a peat core dated back to ~8500 cal year BP in a temperate peatland in Northeast China. Impacted by the tephra during 1160 and 789 cal year BP and climate change, the peatland changed from a fen dominated by vascular plants to a bog dominated by Sphagnum mosses. We used the Clymo model to quantify peat addition rate and decay constant for acrotelm and catotelm layers during both bog and fen phases. Our studied peatland was dominated by Sphagnum fuscum during the bog phase (789 to −59 cal year BP) and lower accumulation rates in the acrotelm layer was found during this phase, suggesting the dominant role of volcanic eruption in the CAR of the peat core. Both mean CAR and NAR were higher during the bog phase than during the fen phase in our study, consistent with the results of the only one similar study in the literature. Because the input rate of organic matter was considered to be lower during the bog phase, the decomposition process must have been much lower during the bog phase than during the fen phase and potentially controlled CAR and NAR. During the fen phase, CAR was also lower under higher temperature and summer insolation, conditions beneficial for decomposition. δ15N of Sphagnum hinted that nitrogen fixation had a positive effect on nitrogen accumulation, particular in recent decades. Our study suggested that decomposition is more important for carbon and nitrogen sequestration than production in peatlands in most conditions and if future climate changes or human disturbance increase decomposition rate, carbon sequestration in peatlands will be jeopardized.
Variations of seed size and seed number per spikelet and their effects on seed germination in hulled oats
Authors: Yuan Zhan , Gislum René , Jing Zhang , Zhifeng Jia , Xiang Ma , Haicong Liu , Rongming Guo , Wei Zhang , Jiaqi Fang , Zhou Qingping , Hui Wang
Published: August 2023

Seed yield components and ear characteristics are critical parameters for seed yield improvement of cereal crops. In this study, 23 hulled oat (Avena sativa) cultivars were planted in four experimental sites during 2018–2020. We determined the ear parameters including the number of four spikelet types, the ear length, the seed weight per ear, and the size of the left and the right seed in the double‐seed spikelet. In addition, five oat cultivars with the highest percentage of the triple‐seed spikelet were selected to evaluate the germination performance of the left, the middle, and the right seed. The results showed that the double‐seed spikelet was present in 73% of the ear, occupying the highest proportion than other spikelet types. The negative correlation showed the trade‐off between total seed number per ear and average seed weight. According to the pathway analysis, the number of double‐seed spikelet had the significantly highest direct effect on the seed weight per ear with the path coefficient of 0.93. In the double‐seed spikelet, the length and the thickness both had significantly positive correlations to the seed weight of the left and the right seeds. The middle seed, which had the smallest seed size, had the lowest germination rate, germination index, vigour index, seedling weight, and length than the right and left seed among three seed positions in the triple‐seed spikelet. We conclude that the double‐seed spikelet number is a key ear characteristic when breeding high‐yielding cultivars.