bluuebunny/crossref_metadata_2025_split huggingface dataset:
Points2Regions: Fast, interactive clustering of imaging‐based spatial transcriptomics data
Authors: Andersson Axel , Behanova Andrea , Avenel Christophe , Windhager Jonas , Malmberg Filip , Wählby Carolina 
Published: July 2024

AbstractImaging‐based spatial transcriptomics techniques generate data in the form of spatial points belonging to different mRNA classes. A crucial part of analyzing the data involves the identification of regions with similar composition of mRNA classes. These biologically interesting regions can manifest at different spatial scales. For example, the composition of mRNA classes on a cellular scale corresponds to cell types, whereas compositions on a millimeter scale correspond to tissue‐level structures. Traditional techniques for identifying such regions often rely on complementary data, such as pre‐segmented cells, or lengthy optimization. This limits their applicability to tasks on a particular scale, restricting their capabilities in exploratory analysis. This article introduces “Points2Regions,” a computational tool for identifying regions with similar mRNA compositions. The tool's novelty lies in its rapid feature extraction by rasterizing points (representing mRNAs) onto a pyramidal grid and its efficient clustering using a combination of hierarchical and ‐means clustering. This enables fast and efficient region discovery across multiple scales without relying on additional data, making it a valuable resource for exploratory analysis. Points2Regions has demonstrated performance similar to state‐of‐the‐art methods on two simulated datasets, without relying on segmented cells, while being several times faster. Experiments on real‐world datasets show that regions identified by Points2Regions are similar to those identified in other studies, confirming that Points2Regions can be used to extract biologically relevant regions. The tool is shared as a Python package integrated into TissUUmaps and a Napari plugin, offering interactive clustering and visualization, significantly enhancing user experience in data exploration.
Actin cytoskeletal regulation of ciliogenesis in development and disease
Authors: Hufft‐Martinez Brittany M. , Wang Henry H. , Saadi Irfan , Tran Pamela V. 
Published: July 2024

AbstractPrimary cilia are antenna‐like sensory organelles that are evolutionarily conserved in nearly all modern eukaryotes, from the single‐celled green alga, Chlamydomonas reinhardtii, to vertebrates and mammals. Cilia are microtubule‐based cellular projections that have adapted to perform a broad range of species‐specific functions, from cell motility to detection of light and the transduction of extracellular mechanical and chemical signals. These functions render cilia essential for organismal development and survival. The high conservation of cilia has allowed for discoveries in C. reinhardtii to inform our understanding of the basic biology of mammalian primary cilia, and to provide insight into the genetic etiology of ciliopathies. Over the last two decades, a growing number of studies has revealed that multiple aspects of ciliary homeostasis are regulated by the actin cytoskeleton, including centrosome migration and positioning, vesicle transport to the basal body, ectocytosis, and ciliary‐mediated signaling. Here, we review actin regulation of ciliary homeostasis, and highlight conserved and divergent mechanisms in C. reinhardtii and mammalian cells. Further, we compare the disease manifestations of patients with ciliopathies to those with mutations in actin and actin‐associated genes, and propose that primary cilia defects caused by genetic alteration of the actin cytoskeleton may underlie certain birth defects.
Brain structure, amyloid, and behavioral features for predicting clinical progression in subjective cognitive decline
Authors: Liu Siwei , Luo Xiao , Chong Joanna Su Xian , Jiaerken Yeerfan , Youn Shim Hee , Zhang Minming , Zhou Juan Helen ,   Alzheimer's Disease Neuroimaging Initiative
Published: July 2024

AbstractAs a potential preclinical stage of Alzheimer's dementia, subjective cognitive decline (SCD) reveals a higher risk of future cognitive decline and conversion to dementia. However, it has not been clear whether SCD status increases the clinical progression of older adults in the context of amyloid deposition, cerebrovascular disease (CeVD), and psychiatric symptoms. We identified 99 normal controls (NC), 15 SCD individuals who developed mild cognitive impairment in the next 2 years (P‐SCD), and 54 SCD individuals who did not (S‐SCD) from ADNI database with both baseline and 2‐year follow‐up data. Total white matter hyperintensity (WMH), WMH in deep (DWMH) and periventricular (PWMH) regions, and voxel‐wise grey matter volumes were compared among groups. Furthermore, using structural equation modelling method, we constructed path models to explore SCD‐related brain changes longitudinally and to determine whether baseline SCD status, age, and depressive symptoms affect participants' clinical outcomes. Both SCD groups showed higher baseline amyloid PET SUVR, baseline PWMH volumes, and larger increase of PWMH volumes over time than NC. In contrast, only P‐SCD had higher baseline DWMH volumes and larger increase of DWMH volumes over time than NC. No longitudinal differences in grey matter volume and amyloid was observed among NC, S‐SCD, and P‐SCD. Our path models demonstrated that SCD status contributed to future WMH progression. Further, baseline SCD status increases the risk of future cognitive decline, mediated by PWMH; baseline depressive symptoms directly contribute to clinical outcomes. In conclusion, both S‐SCD and P‐SCD exhibited more severe CeVD than NC. The CeVD burden increase was more pronounced in P‐SCD. In contrast with the direct association of depressive symptoms with dementia severity progression, the effects of SCD status on future cognitive decline may manifest via CeVD pathologies. Our work highlights the importance of multi‐modal longitudinal designs in understanding the SCD trajectory heterogeneity, paving the way for stratification and early intervention in the preclinical stage.Practitioner Points
Both S‐SCD and P‐SCD exhibited more severe CeVD at baseline and a larger increase of CeVD burden compared to NC, while the burden was more pronounced in P‐SCD.
Baseline SCD status increases the risk of future PWMH and DWMH volume accumulation, mediated by baseline PWMH and DWMH volumes, respectively.
Baseline SCD status increases the risk of future cognitive decline, mediated by baseline PWMH, while baseline depression status directly contributes to clinical outcome.
A multicenter protocol to assess the prognostic significance of the tumor microenvironment in patients with squamous cell carcinoma of the larynx
Authors: De Luca Pietro , Di Stadio Arianna , Petruzzi Gerardo , de Campora Luca , Fior Milena , Moretti Claudio , Della Peruta Vincenzo , Mazzola Francesco , Costarelli Leopoldo , Covello Renato , Ricciardiello Filippo , Tortoriello Giuseppe , Pellini Raul , Radici Marco , Camaioni Angelo 
Published: July 2024

AbstractBackgroundThe purpose of this multicenter study was to retrospectively investigate the prognostic significance of the tumor microenvironment, in relation to survival in a large cohort of patients with laryngeal squamous cell carcinoma (LSCC), using the method proposed by the International TILs Working Group in breast cancer.MethodsAll consecutive patients with biopsy‐proven LSCC who underwent total laryngectomy (TL) between January 2014 and January 2023 were retrospectively included in the study. A retrospective review of medical records including surgical, pathological and follow‐up reports was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group.ResultsThe study group included 186 patients with LSCC. High TILs were statistically correlated with reduced size and extension of primary tumor (pT stage) with a statistically significant value (S: p = 0.01; P: p = 0.0003) and without needs of salvage therapy (S: p = 0.03; P: p = 0.004). Low TILs were indicative of worse prognosis.ConclusionsOur study confirmed the protective value of TILs and the prognostic role of the tumor microenvironment in LSCC; furthermore, our results showed that the score proposed by the International TILs Working Group for breast cancer can be applied to LSCC.
Personalized dendritic cell vaccine in multimodal individualized combination therapy improves survival in high‐risk pediatric cancer patients
Authors: Kyr Michal , Mudry Peter , Polaskova Kristyna , Dubska Lenka Zdrazilova , Demlova Regina , Kubatova Jana , Hlavackova Eva , Pilatova Katerina Cerna , Mazanek Pavel , Vejmelkova Klara , Dusek Vitezslav , Tinka Pavel , Balaz Martin , Merta Tomas , Kuttnerova Zuzana , Turekova Terezia , Pavelka Zdenek , Pokorna Petra , Palova Hana , Mlnarikova Marie , Jezova Marta , Kellnerova Renata , Kozakova Sarka , Slaby Ondrej , Valik Dalibor , Sterba Jaroslav 
Published: July 2024

AbstractA lot of hope for high‐risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single‐agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high‐risk solid tumors using the N‐of‐1 approach in real‐world scenario. A total of 160 evaluable events occurred in 48 patients during the 4‐year follow‐up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check‐point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.
Head‐to‐head comparison of treatment sequences in advanced pancreatic cancer—Real‐world data from the prospective German TPK clinical cohort study
Authors: Marschner Norbert , Haug Nina , Hegewisch‐Becker Susanna , Reiser Marcel , Dörfel Steffen , Lerchenmüller Christian , Linde Hartmut , Wolf Thomas , Hof Anna , Kaiser‐Osterhues Anja , Potthoff Karin , Jänicke Martina ,   the TPK‐Group (Tumour Registry Pancreatic Cancer)
Published: July 2024

AbstractThere are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head‐to‐head phase III randomised trials are missing. We assess real‐world effectiveness of three common sequential treatment strategies by emulating a hypothetical randomised trial. This analysis included 1551 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer receiving FOLFIRINOX (n = 613) or gemcitabine/nab‐paclitaxel (GEMNAB; n = 938) as palliative first‐line treatment. We used marginal structural modelling to compare overall survival (OS) and time to deterioration (TTD) of health‐related quality of life (HRQoL) between three common first‐ to second‐line treatment sequences, adjusting for time‐varying potential confounding. The sequences were: FOLFIRINOX→GEMNAB, GEMNAB→FOLFOX/OFF and GEMNAB→nanoliposomal irinotecan (NALIRI) + 5‐fluorouracil. Outcome was also calculated stratified by patients' prognostic risk according to the Pancreatic Cancer Score. Median OS and TTD of HRQoL independent of risk were 10.7 [8.9, 11.9] and 6.4 [4.8, 7.7] months for FOLFIRINOX→GEMNAB, 8.4 [7.4, 9.7] and 5.8 [4.6, 7.1] months for GEMNAB→FOLFOX/OFF and 8.9 [7.8, 10.4] and 4.6 [4.1, 6.1] months for GEMNAB→NALIRI+5‐fluorouracil. Compared to FOLFIRINOX→GEMNAB, OS and TTD were worse for poor‐risk patients with GEMNAB→FOLFOX/OFF (OS: HR 2.09 [1.47, 2.98]; TTD: HR 1.97 [1.19, 3.27]) and those with GEMNAB→NALIRI+5‐fluorouracil (OS: HR 1.35, [0.76, 2.39]; TTD: HR 2.62 [1.56, 4.42]). Brackets denote 95%‐confidence intervals. The estimated real‐world effectiveness of the three treatment sequences evaluated were largely comparable. Poor‐risk patients might benefit from intensified treatment with FOLFIRINOX→GEMNAB in terms of clinical and patient‐reported outcomes. Future randomised trials on sequential treatments in advanced pancreatic cancer are warranted.
A cross‐sectional study of anterior cutaneous nerve entrapment syndrome at a Japanese emergency department
Authors: Kano Yasuhiro , Komagamine Junpei , Murata Kengo 
Published: July 2024

AbstractBackgroundAnterior cutaneous nerve entrapment syndrome (ACNES) is the most common cause of abdominal wall pain. This study aimed to clarify the proportion of ACNES cases among those of abdominal pain and the clinical characteristics and prognosis of the disease in an emergency department (ED) of a Japanese general hospital.MethodsThe medical records of patients from January 2014 to December 2023 were reviewed, and patients aged 15 years or older with abdominal pain with positivity for Carnett's sign, a good response to trigger point injection (TPI), and an ACNES diagnosis were included. The proportion of ACNES cases among the complaints related to abdominal pain in the ED between 2020 and 2023 was then determined. The recurrence rate was also determined using data from the medical records and telephone follow‐ups.ResultsTwenty‐one patients were included. Their median age was 50 years (range: 16–83 years), 13 (62%) were female, and 11 (52%) had acute‐onset pain. Follow‐up data were available for 11 patients (52%), seven (64%) of whom had recurrent pain for a median period of 1 week after the index visit. The proportion of ACNES cases among those of abdominal pain was 0.11%.ConclusionACNES might be uncommon among patients with abdominal pain in the ED setting although underdiagnosis of this condition might have led to an underestimation of the proportion of cases. Moreover, given the high recurrence rate of abdominal pain associated with ACNES, following up these patients is very important.
Weight loss and dysgeusia in relapsed/refractory multiple myeloma patients treated with talquetamab
Authors: Naqvi Syed , Shrestha Asis , Alzubi Marah , Alrawabdeh Jawad , Thanendrarajan Sharmilan , Zangari Maurizio , van Rhee Frits , Schinke Carolina , Al Hadidi Samer 
Published: July 2024

AbstractTalquetamab is an approved therapy for relapsed multiple myeloma. This study examined dysgeusia and weight loss occurrences, alongside investigating symptom reversibility post‐treatment cessation. Dysgeusia was prevalent, persisting in 15% of patients. On average, patients lost 6% of their weight during treatment, with weight loss persisting in about half of the patients post‐discontinuation. Weight loss and dysgeusia are important adverse events to consider while on talquetamab treatment. Extending dose intervals can potentially prevent such adverse events and should be studied in future prospective clinical trials.
The recent increasing frequency of strong cooling event in Southwest China in February
Authors: Chang Sun , Zi‐Niu Xiao 
Published: July 2024

AbstractA strong cooling event refers to a sharp change in the average temperature over a short period. The rapid change of temperature has important effect on human health and is highly concerned recent years. Based on the observed temperature data set from stations in Southwest China (SWC) from 1979 to 2017, this paper analyses the characteristics of the strong cooling event (SCE). The result shows that SCE occurs with the highest frequency during the time from February to May. Among them, the frequency of SCE in February exhibits an abrupt change before and after 2005 with a significant increase. Further study reveals that the change of SCE frequency in February is associated with the large‐scale background circulation patterns. After 2005, there is a cyclonic circulation anomaly in Northeast Asia and an anticyclonic circulation anomaly in the Tibet Plateau (TP). This pattern provides a favourable condition for the southward movement of cold air mass, thereby increasing the frequency of SCE in SWC. Furthermore, it is revealed that there is a strong correlation between the variation of SCE frequency in February and sea surface temperatures (SST) in the Northwest Pacific in January before 2005. The cold SST anomaly could favour the occurrence of extreme TD events in SWC through vertical circulation. After 2005, the correlation between SCE and Northwest Pacific SST is not significant. The sea ice in the northern Barents Sea and Kara Sea becomes the dominant impact factor. The abnormally low sea ice concentration is conducive to strengthen the meridional circulation over East Asia, leading to an increasing frequency of SCE in SWC.
Synthesis and Viscoelastic Properties of Polycaprolactone/Polyvinylidene Fluoride/Nanohydroxyapatite Composite Scaffolds
Authors: Yeganeh Kari Ali , Nezhadfard Mahla Sadat , Montazeri Arash , Pishvaei Malihe 
Published: July 2024

AbstractObtaining a polymer nanocomposite with optimum viscoelastic, thermal, and biocompatibility properties is the main objective when designing nanocomposite systems with potential applications in tissue engineering. For this purpose, a blend of Polycaprolactone (PCL) and Polyvinylidene fluoride (PVDF) in an 85/15 weight ratio, along with a nanocomposite reinforced by nanohydroxyapatite (nHA) particles, is fabricated using a solution casting method in a mold. The impact of nHA content on crystallinity, viscoelastic properties, thermal stability, and the properties–structure relationship of nanocomposites is evaluated using scanning electron microscopy (SEM). Dynamic mechanical thermal (DMTA) analysis is used to determine the William–Landel–Ferry (WLF) constants and the effect of nHA on the nanocomposite's viscoelastic behavior. The PCL/15PVDF/0.5 wt% nHA exhibits the maximum thermal stability (40% residual char value) and 95% increase in storage modulus at 90 °C (rubbery region) in comparison with PCL/15PVDF blend. Water contact angle (WCA) and biocompatibility tests are conducted on the PCL/15PVDF blend and nanocomposite scaffolds to design appropriate nanocomposite systems with potential applications in tissue engineering. The high hydrophilic properties are assigned to PCL/15PVDF/0.5 wt% nHA with a WCA of 67.5°. Finally, in vitro cell culture confirmed 0.5 wt% nHA significantly improves cell adhesion and cytotoxicity with MG‐63 cells.
Best Ulam constants for two‐dimensional nonautonomous linear differential systems
Authors: Anderson Douglas R. , Onitsuka Masakazu , O'Regan Donal 
Published: July 2024

AbstractThis study deals with the Ulam stability of nonautonomous linear differential systems without assuming the condition that they admit an exponential dichotomy. In particular, the best (minimal) Ulam constants for two‐dimensional nonautonomous linear differential systems with generalized Jordan normal forms are derived. The obtained results are applicable not only to systems with solutions that exist globally on , but also to systems with solutions that blow up in finite time. New results are included even for constant coefficients. A wealth of examples are presented, and approximations of node, saddle, and focus are proposed. In addition, this is the first study to derive the best Ulam constants for nonautonomous systems other than periodic systems.
Single‐cell transcriptome dissecting the microenvironment remodeled by PD1 blockade combined with photodynamic therapy in a mouse model of oral carcinogenesis
Authors: Dong Yunmei , Zeng Kan , Ai Ruixue , Zhang Chengli , Mao Fei , Dan Hongxia , Zeng Xin , Ji Ning , Li Jing , Jin Xin , Chen Qianming , Zhou Yu , Li Taiwen 
Published: July 2024

AbstractOral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4‐nitroquinoline 1‐oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single‐cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor‐promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor‐promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment‐associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.
Management from a multidisciplinary perspective of phlebitis related to peripheral venous catheter insertion: An international Delphi study
Authors: Torné‐Ruiz Alba , Sanromà‐Ortiz Montse , Corral‐Nuñez Alex , Medel Daniel , Roca Judith , García‐Expósito Judith 
Published: July 2024

AbstractAimTo determine the consensus and importance of care practices related to the management of peripheral venous catheter (PVC)‐related phlebitis in hospitalized patients through the views of experts from different disciplines.BackgroundPVCs are commonly used in hospitals but are associated with complications such as phlebitis. Their management differs widely, and studies are heterogeneous.DesignDelphi method.MethodsFour stages: problem area (with Web of Science bibliometric review in July 2022), panel members, two Delphi rounds and closing criteria. In the Delphi survey, experts answered an online questionnaire based on assessment, treatment and follow‐up dimensions (September 2022–February 2023). Statistical analyses were conducted of frequencies, percentages, measures of central tendency and levels of dispersion (QD). A space for comments was created, and a thematic analysis conducted of them.ResultsEighteen experts (nurses, doctors and pharmacists) participated in the Delphi rounds. Forty‐five activities were identified: 19 in assessment, 15 in treatment and 11 in follow‐up. A high consensus level (QD ≤ 0.6) was found in five activities (11.12%), moderate level (0.6 < QD < 1.0) in 19 (42.22%) and low level (QD > 1.0) in 21 (46.66%). Seven themes were determined (patient perspective, lack of consensus, low evidence‐based practices, stage‐based treatments, prevention activities, high variability in practice and specialist teams and interdisciplinary work).ConclusionThe importance of systematic assessment scales is highlighted together with consensus on signs and symptoms (pain, redness, inflammation, palpable cord and induration). Treatment according to severity and daily visual recording and monitoring are emphasized along with the need for patient participation and healthcare literacy. A high level of consensus was obtained in 11% of the activities, showing the large variability of criteria and interventions for phlebitis management. Highlighted needs include working in a team, the use of specialist teams and promoting evidence‐ and prevention‐based activities.Relevance to Clinical PracticeClinical variability is noted and, therefore, the importance of consensus on standardized care for PVC phlebitis and evidence‐based practice.Reporting MethodDelphi studies (CREDES).Patient or Public ContributionExperts contribution.