bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Financial Validation of the International Study Group for Pancreatic Surgery (ISGPS) Definition of Post-Pancreatectomy Acute Pancreatitis (PPAP)
Authors: Bannone Elisa , Cattelani Alice , Corvino Gaetano , Marchetti Alessio , Andreasi Valentina , Fermi Francesca , Partelli Stefano , Pecorelli Nicolò , Tamburrino Domenico , Esposito Alessandro , Malleo Giuseppe , Bhandare Manish , Gundavda Kaival , Jiang Kuirong , Lu Zipeng , Yin Jie , Lavu Harish , Klotz Rosa , Merz Daniela , Michalski Christoph , Klaiber Ulla , Montorsi Marco , Nappo Gennaro , Ikenaga Naoki , Scornamiglio Pasquale , Andersson Bodil , Jeffery Fraser , Halloran Daniel , Padbury Robert , Siriwardena Ajith K. , Barreto Savio George , Gianotti Luca , Oláh Attila , Halloran Christopher M. , Connor Saxon , Andersson Roland , Izbicki Jakob R. , Nakamura Masafumi , Zerbi Alessandro , Abu Hilal Mohammad , Loos Martin , Yeo Charles J. , Miao Yi , Falconi Massimo , Dervenis Christos , Neoptolemos John P. , Büchler Markus W. , Besselink Marc G. , Ferrone Cristina , Hackert Thilo , Salvia Roberto , Shrikhande Shailesh V. , Strobel Oliver , Werner Jens , Wolfgang Christopher L. , Marchegiani Giovanni ,   for the International Study Group for Pancreatic Surgery (ISGPS)
Published: October 2024

Objective:
To validate the ISGPS definition and grading system of PPAP after pancreatoduodenectomy (PD).

Summary Background Data:
In 2022, the International Study Group for Pancreatic Surgery (ISGPS) defined post-pancreatectomy acute pancreatitis (PPAP) and recommended a prospective validation of its diagnostic criteria and grading system.

Methods:
This was a prospective, international, multicenter study including patients undergoing PD at 17 referral pancreatic centers across Europe, Asia, Oceania, and the United States. PPAP diagnosis required the following three parameters: (1) postoperative serum hyperamylasemia /hyperlipasemia (POH) persisting on postoperative days 1 and 2, (2) radiologic alterations consistent with PPAP, and (3) a clinically relevant deterioration in the patient’s condition. To validate the grading system, clinical and economic parameters were analyzed across all grades.

Results:
Among 2902 patients undergoing PD, 7.5% (n=218) developed PPAP (6.3% grade B and 1.2% grade C). POH occurred in 24.1% of patients. Hospital stay was associated with PPAP grades (No POH/PPAP 10 days (IQR 7-17) days, grade B 22 days (IQR 15-34) days, and grade C 43 days (IQR 27-54) days; P<0.001), as well as intensive care unit admission (No POH/PPAP 5.4%, grade B 12.6%, grade C 82.9%; P<0.010), and hospital readmission rates (No POH/PPAP 7.3%, grade B 16.1%, grade C 18.5%; P<0.05). Costs of grade B and C PPAP were 2 and 11 times greater than uncomplicated clinical course, resp. (P<0.001).

Conclusions:
This first prospective, international validation study of the ISGPS definition and grading system for PPAP highlighted the relevant clinical and financial implications of this condition. These results stress the importance of routine screening for PPAP in patients undergoing PD.
Neuronal TDP-43 aggregation drives changes in microglial morphology prior to immunophenotype in amyotrophic lateral sclerosis
Authors: Swanson Molly E. V. , Mrkela Miran , Turner Clinton , Curtis Maurice A. , Faull Richard L. M. , Walker Adam K. , Scotter Emma L. 
Published: October 2024

AbstractMicroglia are the innate immune cells of the brain with the capacity to react to damage or disease. Microglial reactions can be characterised in post-mortem tissues by assessing their pattern of protein expression, or immunophenotypes, and cell morphologies. We recently demonstrated that microglia have a phagocytic immunophenotype in early-stage ALS but transition to a dysfunctional immunophenotype by end stage, and that these states are driven by TAR DNA-binding protein 43 (TDP-43) aggregation in the human brain. However, it remains unclear how microglial morphologies are changed in ALS. Here we examine the relationship between microglial immunophenotypes and morphologies, and TDP-43 pathology in motor cortex tissue from people with ALS and from a TDP-43-driven ALS mouse model. Post-mortem human brain tissue from 10 control and 10 ALS cases was analysed alongside brain tissue from the bigenicNEFH-tTA/tetO-hTDP-43ΔNLS (rNLS) mouse model of ALS at distinct disease stages. Sections were immunohistochemically labelled for microglial markers (HLA-DR, CD68, and Iba1) and phosphorylated TDP-43 (pTDP-43). Single-cell microglial HLA-DR, CD68, and Iba1 average intensities, and morphological features (cell body area, process number, total outgrowth, and branch number) were measured using custom image analysis pipelines. In human ALS motor cortex, we identified a significant change in microglial morphologies from ramified to hypertrophic, which was associated with increased Iba1 and CD68 levels. In the rNLS mouse motor cortex, the microglial morphological changed from ramified to hypertrophic and increased Iba1 levels occurred in parallel with pTDP-43 aggregation, prior to increases in CD68 levels. Overall, the evidence presented in this study demonstrates that microglia change their morphologies prior to immunophenotype changes. These morphological changes may prime microglia near neurons with pTDP-43 aggregation for phagocytosis, in turn triggering immunophenotype changes; first, to a phagocytic state then to a dysfunctional one.
Deletions Rate-Limit Breast and Ovarian Cancer Initiation
Authors: Houlahan Kathleen E. , Bihie Mahad , Contreras Julián Grandvallet , Fulop Daniel J. , Lopez Gonzalo , Huang Hsin-Hsiung , Van Loo Peter , Curtis Christina , Boutros Paul C. , Huang Kuan-lin 
Published: October 2024

ABSTRACTOptimizing prevention and early detection of cancer requires understanding the number, types and timing of driver mutations. To quantify this, we exploited the elevated cancer incidence and mutation rates in germlineBRCA1andBRCA2 (gBRCA1/2)carriers. Using novel statistical models, we identify genomic deletions as the likely rate-limiting mutational processes, with 1-3 deletions required to initiate breast and ovarian tumors.gBRCA1/2-driven hereditary and sporadic tumors undergo convergent evolution to develop a similar set of driver deletions, and deletions explain the elevated cancer risk ofgBRCA1/2-carriers. Orthogonal mutation timing analysis identifies deletions of chromosome 17 and 13q as early, recurrent events. Single-cell analyses confirmed deletion rate differences ingBRCA1/2vs. non-carrier tumors as well as cells engineered to harborgBRCA1/2. The centrality of deletion-associated chromosomal instability to tumorigenesis shapes interpretation of the somatic evolution of non-malignant tissue and guides strategies for precision prevention and early detection.
The non-hallucinogenic serotonin 1B receptor is necessary for the antidepressant-like effects of psilocybin in mice
Authors: Fleury Sixtine , Nautiyal Katherine M. 
Published: October 2024

AbstractRecent studies highlight the promising use of psychedelic therapies for psychiatric disorders, including depression. The persisting clinical effects of psychedelics such as psilocybin are commonly attributed to activation of the serotonin 2A receptor (5-HT2AR) based on its role in the acute hallucinatory effects. However, the active metabolite of psilocybin binds to many serotonin receptor subtypes, including the serotonin 1B receptor (5-HT1BR). Given the known role of 5-HT1BR in mediating depressive phenotypes and promoting neural plasticity, we hypothesized that it mediates the effects of psilocybin on neural activity and behavior. We first examined the acute neural response to psilocybin in mice lacking 5-HT1BR. We found that 5-HT1BR expression influenced brain-wide activity following psilocybin administration, measured by differences in the patterns of the immediate early gene c-Fos, across regions involved in emotional processing and cognitive function, including the amygdala and prefrontal cortex. Functionally, we demonstrated that 5-HT1BR is necessary for the acute and persisting behavioral effects of psilocybin. Although there was no effect of 5-HT1BR expression on the acute head twitch response, mice lacking 5-HT1BRs had attenuated hypolocomotor responses to psilocybin. We also measured the persisting antidepressant-like effects of psilocybin using transgenic and pharmacological 5-HT1BR loss-of-function models and found that 5-HT1B was required for the decreased anhedonia and reduced anxiety-like behavior. Finally, using a network analysis, we identified neural circuits through which 5-H1BR may modulate the response to psilocybin. Overall, our research implicates the 5-HT1BR, a non-hallucinogenic serotonin receptor, as a critical mediator of the behavioral and neural effects of psilocybin in mice.Significance StatementPsilocybin, the active ingredient of ‘magic mushrooms’ has emerged as a potential fast-acting and long-lasting antidepressant. As a classic psychedelic, it is unclear what mechanisms of actions underlie its antidepressant effects or if the subjective conscious experience is necessary. While 5-HT2AR-mediated effects are most commonly implicated given its role in the hallucinogenic effect, the polypharmacology of psilocybin is likely critical for its complex behavioral effects. Our studies show the necessity of a non-hallucinatory serotonin receptor, 5-HT1BR, in the antidepressant response to psilocybin, and highlight a potential target for the development of effective non-hallucinogenic pharmacotherapies for the treatment of depressive disorders.
Foamy microglia link oxylipins to disease progression in multiple sclerosis
Authors: van der Vliet Daan , Di Xinyu , Shamorkina Tatiana M. , Pavlovic Anto , van der Vliet Iris A.C.M. , Zeng Yingyu , Macnair Will , van Egmond Noëlle , Chen J.Q. Alida , van den Bosch Aletta M.R. , Engelenburg Hendrik J. , Mason Matthew R.J. , Coulon-Bainier Claire , Gagestein Berend , Dusseldorp Elise , van Eijk Marco , Grether Uwe ,   The Netherlands Brain Bank, Harms Amy C. , Hankemeier Thomas , Collin Ludovic , Heck Albert J.R. , Huitinga Inge , van der Stelt Mario 
Published: October 2024

AbstractMultiple sclerosis (MS) is a neuroinflammatory disease characterized by expanding demyelinating lesions, leading to severe and irreversible disability. The mechanisms driving lesion expansion, however, remain poorly understood. Here, using a multi-omics approach, we identified foamy microglia as primary contributors to the molecular profile of lesions and disease progression in secondary progressive MS. Lesions with foamy microglia are marked by the accumulation of cholesterol esters, bismonoacylglycerolphosphates (BMP), and oxylipins, along with high B-cell infiltration, increased levels of immunoglobulin G1, and elevated expression of Fcγ- and complement receptors. Lesions with foamy GPNMB+-microglia display markers of enhanced phagocytosis, lipid metabolism, lysosomal dysfunction, and antigen presentation, but lack classical pro-inflammatory markers. Our data suggest that sustained phagocytosis of myelin overwhelms microglial endo-lysosomal capacity, leading to lipid droplet and oxylipin formation. This microglial phenotype may induce further recruitment of adaptive immune cells, axonal damage, drive lesion expansion and prevent remyelination. Monoacylglycerol lipase, involved in producing oxylipin precursors, was identified as a potential therapeutic target to disrupt this cycle and prevent chronic lesion expansion.
Evolutionary macroecology: Incorporating phylogenetic information more explicitly into process-based, forward time, simulation models
Authors: Culshaw Victoria , Rangel Thiago F.L.V.B. , Sanmartín Isabel 
Published: October 2024

AbstractA conceptual and mechanistic approach for bridging the fields of macroecology (ecological biogeography) and historical biogeography has been a long-term aim in Evolutionary Biology. Such a bridge could increase our understanding on the processes governing the spatial and temporal generation of biodiversity distribution patterns. This aim has been recently approached from the perspective of evolutionary biogeographic inferential statistical models, within a maximum likelihood or Bayesian framework, which incorporates the contribution of environmental factors as scaling parameters. Here, we describe a new approach that builds on a spatially-explicit, forward-time, computer simulation (“automat”) model. The model sets a series of rules by which speciation, extinction, and dispersal of lineages are governed within an environmentally heterogeneous, two-dimensional gridded landscape. Unlike some previous approaches, niche conservatism is assumed but the model allows for environmental conditions to vary both spatially and temporally, by letting the model run over three time-series of actual palaeoclimate data, spanning the last 20 million years of geological history. Speciation is governed by a global speciation rate, whereas the background extinction rate is made dependent on abiotic (palaeoenvironmental conditions) and biotic (species density per grid cell) factors, hence giving a local background extinction rate. Also, we propose a novel mechanistic approach in which species are not the result of unique, independent events but linked through evolutionary history from a single evolutionary origin. We set different rules to generate the resulting phylogenies to test different factors (time, environment) that govern the inheritance of range distributions. Dispersal follows a simple Poisson kernel model, with higher probability of migration to contiguous grid cells and rare long-distance movements to distant cells. We also describe ways in which the presence of temporal dispersal barriers could modify the resultant spatial patterns. Evaluation of model accuracy and fit is based on comparison of simulated spatial patterns with observed, empirical ones. We use statistic dependent variables such as the spatial distribution of species in the landscape, species’ geographic range size and location, and the shape of the resultant phylogenies. Finally, we propose that this spatially-explicit simulation model could be used to evaluate the role played by niche conservatism, ecological vicariance and climatic-driven extinction in the generation of disjunct continental patterns, such as the presence of sister-lineages in numerous families of angiosperms forming a ring in the continental margins of the African continent, the Rand Flora pattern.
Simulated climate warming scenarios lead to earlier emergence and increased weight loss but have no effect on overwintering survival in solitary bees
Authors: Möllmann Jannik S. , Lörchner Liv , Hodapp Dean , Knuf Ina , Xu Hongfei , Colgan Thomas J. 
Published: October 2024

AbstractInsect pollination is critical for both wildflower stability and agricultural yields, with solitary bees being a group of pollinators of fundamental importance. However, documented declines in populations, exacerbated by environmental pressures, including climate change, pose significant threats to the provision of ecosystem services. Exposure to elevated temperatures during periods of dormancy, such as overwintering, is predicted to lead to phenological shifts, changes in condition, and impacts on survival. However, we currently lack studies that inform how such aspects are affected in future climate change scenarios. Using simulated temperature regimes informed by predictions of the Intergovernmental Panel on Climate Change, we exposed overwintering mason bees (Osmiaspecies) to three field-relevant temperature profiles based on either present-day overwintering temperatures or future temperatures predicted under two major climate warming scenarios (SSP2-4.5 and SSP5-8.5) and measured how temperature exposure affected emergence timing, weight loss and survival. We found that exposure to temperatures under intermediate and worst-case climate warming scenarios led to earlier emergence by approximately three and six weeks, respectively, with increasing divergences in timing of emergence between the sexes ofOsmia bicornis, which may lead to intraspecific phenological mismatches. While we found no effect of temperature on overwintering survival rates, we observed increased weight loss prior to emergence but found that in contrast to other studies, it only mildly mediated shifts in emergence timing brought about by temperature exposure, suggesting that weight loss is unlikely to play a major role as a trigger of emergence timing in mason bees. Our study contributes to the growing literature highlighting the impact that temperatures under climate change models will have on the timing of key life events for essential pollinators, which may have consequences at the population and community levels.
Inducible, but not constitutive, pancreaticREG/Regisoforms are regulated by intestinal microbiota and pancreatic diseases
Authors: Zhou Yixuan , Komnick Macy R. , Sepulveda Fabiola , Liu Grace , Nieves-Ortiz Elida , Meador Kelsey , Ndatabaye Ornella , Fatkhullina Aliia , Wu-Woods Natalie J. , Naydenkov Paulina M. , Kent Johnathan , Christiansen Nathaniel , Madariaga Maria L , Witkowski Piotr , Ismagilov Rustem F. , Esterházy Daria 
Published: October 2024

AbstractTheREG/Reggene locus encodes for a conserved family of potent antimicrobial but also pancreatitis-associated proteins. Here we investigated whetherREG/Regfamily members differ in their baseline expression levels and abilities to be regulated in the pancreas and gut upon perturbations. We found, in human and mouse, pancreas and gut differed inREG/Regisoform levels and preferences, with duodenum most resembling the pancreas. Pancreatic acinar cells and intestinal enterocytes were the dominant REG producers. Intestinal symbiotic microbes regulated the expression of the same, selectRegmembers in gut and pancreas. TheseRegmembers had the most STAT3-binding sites close to the transcription start sites and were partially IL-22 dependent. We thus categorized them as “inducible” and others as “constitutive”. Indeed, also in models of pancreatic-ductal adenocarcinoma and pancreatitis, only inducibleRegmembers were upregulated in pancreas. While intestinalRegexpression remained unchanged upon pancreatic perturbation, pancreatitis altered the microbial composition of the duodenum and feces shortly after disease onset. Our study reveals differential usage and regulation ofREG/Regisoforms as a mechanism for tissue-specific innate immunity, highlights the intimate connection of pancreas and duodenum, and implies a gut-to-pancreas communication axis resulting in a coordinatedRegresponse.
Deficiency of Hv1 Proton Channel Enhances Macrophage Antigen Presentation and Anti-Tumor Responses in Glioma
Authors: Zheng Jiaying , Wang Lingxiao , Zhao Shunyi , Ayasoufi Katayoun , Goddery Emma , Strege Peter R. , Wan Yushan , Zhang Wenjing , Xie Manling , Beyder Arthur , Johnson Aaron J. , Wu Long-Jun 
Published: October 2024

ABSTRACTIn the tumor microenvironment of glioblastoma, myeloid cells act as a double-edged sword—they are a major cellular component modulating the immune response while presenting a potential therapeutic target. Our study highlights the voltage-gated proton channel Hv1, predominantly expressed in myeloid cells, as a crucial regulator of their physiological functions. We discovered a strong correlation between increased Hv1 expression and poor prognosis in glioblastoma patients. Depleting Hv1 significantly extended survival in a mouse model of glioma. Employing multiple novel transgenic mouse lines, we demonstrated that Hv1 is upregulated in response to tumor presence, with glioma-associated macrophages as the principal contributors. Specifically, we identified that Hv1 in infiltrating macrophages as the major driver of survival phenotype differences. Through a combination ofin vivotwo-photon imaging, spectral flow cytometry, and spatial transcriptomic sequencing, we found that Hv1 depletion leads to reduced macrophage infiltration and enhanced antigen presentation, ultimately fostering a stronger adaptive immune response. These findings establish the Hv1 channel as a crucial new immune regulator within the brain tumor milieu, offering a promising target for reprogramming macrophage function to combat glioblastoma.
Associations between Psychological Factors and Long-Term Dizziness Handicap in Vestibular Schwannoma Patients: A Cross-Sectional Study
Authors: Rutenkröger M. , Scheer M. , Rampp S. , Strauss C. , Schönfeld R. , Leplow B. 
Published: October 2024

AbstractBackgroundVestibular schwannoma (VS) often results in persistent dizziness that negatively impacts quality of life (QoL). While physical effects are well-documented, the influence of psychological factors on dizziness severity is less studied. This study investigates how psychological characteristics affect dizziness in VS patients.MethodsIn this cross-sectional study, 93 VS patients were analyzed, with 77 (82.8%) reporting postoperative dizziness. Psychological factors, including premorbid disorders, personality traits, somatization, and current depression and anxiety levels, were assessed using self-report questionnaires. Correlations between these factors and dizziness severity, measured by the Dizziness Handicap Inventory (DHI), were examined.ResultsPatients with postoperative dizziness had higher depression levels and a greater prevalence of preoperative dizziness compared to those without postoperative dizziness. Significant correlations were found between dizziness severity and psychological factors: conscientiousness (r = .30, p = .03), social support (r = .32, p = .03), and the HADS total score (r = .36, p = .01). Emotional aspects of dizziness (DHI-E) were correlated with somatization (r = .27, p = .04) and anxiety (r = .40, p = .01). Functional aspects (DHI-F) were linked to conscientiousness (r = .31, p = .03) and depression (r = .26, p = .06).ConclusionPsychological factors significantly impact dizziness severity in VS patients. Incorporating psychological assessments and interventions, such as cognitive-behavioral therapy and combined vestibular and psychological rehabilitation, may improve treatment outcomes and QoL. Further research is needed to assess the effectiveness of these approaches and their impact on the relationship between psychological factors and dizziness.