bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organ weights and length anthropometry measures at autopsy for sudden infant death syndrome cases and other infant deaths in the Chicago infant mortality study
Authors: Mychaleckyj Josyf C. , Normeshie Cornelius , Keene Keith L. , Hauck Fern R. 
Published: July 2024

AbstractOrgan weights are a possible diagnostic or pathophysiological clue to distinguishing sudden infant death syndrome (SIDS) cases from other infant deaths but suffer from major confounding. Using autopsy data from the Chicago Infant Mortality Study, a majority African‐American case–control study of deceased infants under 1 year conducted 1993–96, we assessed differences in the weights of brain, thymus, kidneys, lungs, liver, spleen, total body, and four length anthropometry measures in SIDS‐diagnosed infants compared to controls. Using exact and coarsened matching, we ran Bayesian linear models with these anthropometry outcomes and repeated the analyses substituting the corresponding fitted allometrically‐scaled organ weight indices to account for body size. After detailed analysis and adjustment for potential confounders, we found that matched SIDS infants were generally bigger than controls, with higher mean brain, liver, spleen, thymus, lung, and total body weights, and higher mean head and chest circumference, crown‐heel, crown‐rump lengths. SIDS infants also had higher mean thymus, liver, spleen, lung and total body weight indices. The association with thymus weight was proportionately greater in magnitude than any other outcome measure and independent of body size. The results of these more detailed analyses are consistent with recent findings from other studies with differing racial compositions, and substantially confirm the primary organ sites for more detailed mechanistic research into the biological dysregulation contributing to underlying pathophysiology of SIDS.
Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis
Authors: Pingree Graham , Bentan Mihai , Fitzpatrick Thomas , Schuman Theodore 
Published: July 2024

AbstractBackgroundElexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear.MethodsThe TriNetX Analytics Research Network, consisting of 120 million global de‐identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA‐approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF‐related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS.ResultsETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5–2.75; p‐value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54–5.85; p‐value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non‐CFTR modulator groups, except for reduced CF‐related pulmonary exacerbations from 0 to 6 months post‐FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators.ConclusionsIn a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.
The role of revision sinus surgery in the initiation of dupilumab therapy: A real‐world study of molecular and cellular features
Authors: Gaffar Abigail , Alenezi Abdul Rahman , Kelly Kathleen M. , Kulaga Heather M. , Keng Hsin‐Tzu , Smith Amy , Lane Andrew P. 
Published: July 2024

Key points
A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab.
Revision sinus surgery immediately prior to dupilumab reduces long‐term interleukin (IL)‐4/IL‐13 tissue mRNA.
Pre‐dupilumab revision surgery is associated with reduced tissue eosinophils and GATA‐3+ cells.
Nanoscale flow cytometry‐based quantification of blood‐based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease
Authors: Dayarathna Thamara , Roseborough Austyn D. , Gomes Janice , Khazaee Reza , Silveira Carolina R. A. , Borron Kathy , Yu Soojung , Coleman Kristy , Jesso Sarah , Finger Elizabeth , MacDonald Penny , Borrie Michael , Wells Jennie , Bartha Robert , Zou Guangyong , Whitehead Shawn N. , Leong Hon S. , Pasternak Stephen H. 
Published: July 2024

AbstractINTRODUCTIONAccurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure.METHODSWe developed a nanoscale flow cytometry (nFC)‐based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls.RESULTSCirculating amyloid beta (Aβ), tau, phosphorylated tau (p‐tau)181, p‐tau231, p‐tau217, p‐tauS235, ubiquitin, and lysosomal‐associated membrane protein 1–positive EVs distinguished AD samples. p‐tau181, p‐tau217, p‐tauS235, and ubiquitin‐positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p‐tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p‐tauS235.DISCUSSIONThis nFC‐based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC‐based measurements in larger populations and comparison to “gold standard” biomarkers is an exciting next step for developing AD diagnostic tools.HIGHLIGHTS
Extracellular vesicles represent promising biomarkers of Alzheimer's disease (AD) that can be measured in the peripheral circulation.
This study demonstrates the utility of nanoscale flow cytometry for the measurement of circulating extracellular vesicles (EVs) in AD blood samples.
Multiple markers including amyloid beta, tau, phosphorylated tau (p‐tau)181, p‐tau231, p‐tau217, and p‐tauS235 accurately distinguished AD samples from healthy controls.
Future studies should expand blood and cerebrospinal fluid–based EV biomarker development using nanoflow cytometry approaches.
Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review
Authors: Zhu Zihan , Deng Xinyi , Xie Wenqing , Li Hengzhen , Li Yusheng , Deng Zhenhan 
Published: July 2024

AbstractThis review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G‐90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti‐inflammatory, analgesic, antioxidant, wound‐healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid‐modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G‐90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well‐developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.
Pfadunabhängiges mit sichtbarem Licht adressierbares orthogonales Photoschalten für Anwendungen in multi‐photochromomen Polymeren und molekularen Computern
Authors: Köttner Laura , Dube Henry 
Published: July 2024

AbstractSynthetische molekulare Photoschalter sind als hochpräzise Werkzeuge zur Einführung von Lichtadressierbarkeit auf kleinster Ebene in den Mittelpunkt der Forschung gerückt. Heute sind sie in allen Bereichen der angewandten Chemie zu finden, sei es in der Materialforschung, chemischen Biologie, Katalyse oder Nanotechnologie. Für einen nächsten Schritt in der Anwendbarkeit ist vollständig orthogonales Photoschalten besonders wünschenswert, aber bis heute ist eine solche unabhängige Adressierbarkeit verschiedener Photoschalter eine große Herausforderung. In dieser Arbeit präsentieren wir das erste Beispiel für ein vollständig durch sichtbares Licht adressierbares und pfadunabhängiges orthogonales Photoschalten. Durch die Kombination von zwei kürzlich entwickelten indigoiden Photoschaltern – ein peri‐Anthracenthioindigo und ein auf Rhodanin‐basiertes Chromophor – wird ein Schaltsystem mit vier Zuständen geschaffen, wobei jeder Zustand in hoher Ausbeute völlig unabhängig und ausnahmslos mit sichtbarem Licht angesteuert werden kann. Die vier Zustände führen zu vier verschiedenen Farben, die auf eine feste Polymermatrix übertragen werden können, wodurch ein vielseitiges photochromes Material mit multiplen Zuständen entsteht. Darüber hinaus wird die Kombination mit einem Fluoreszenzfarbstoff als dritter Komponente gezeigt, was die Anwendbarkeit dieses orthogonalen Photoschaltersystems in der molekularen Logik und Informationsverarbeitung ermöglicht.
Asymmetric Paired Electrolysis: Enantioselective Alkylation of Sulfonylimines via C(sp3)−H Functionalization
Authors: Tao Yongsheng , Ma Wan , Sun Rui , Huang Cheng , Lu Qingquan 
Published: July 2024

AbstractEnantioselective transformation of ubiquitous C(sp3)−H bonds into three‐dimensional chiral scaffolds is of longstanding interest to synthetic chemists. Herein, an asymmetric paired electrolysis enables a highly efficient and sustainable approach to the enantioselective alkylation of sulfonylimines via C(sp3)−H functionalization. In this protocol, anodic oxidation for benzylic radical formation and Lewis acid‐catalyzed sulfonylimine reduction on the cathode were seamlessly cross‐coupled (up to 88 % yield). Enantioenriched chiral amines containing a tetrasubstituted carbon stereocenter are accessed with high enantioselectivity (up to 96 % ee). Mechanistic studies suggest that the amine generated in situ could serve as a base to deprotonate phenols and decrease the oxidation potential of the reaction, allowing phenols with lower potentials to be preferentially oxidized.
A Modified Arbuzov‐Michalis Reaction for Selective Alkylation of Nucleophiles
Authors: Wang Jia‐Xi , Chen Mu‐Qiu , Zhang Yang , Han Bo , Mou Ze‐Dong , Feng Xitong , Zhang Xia , Niu Dawen 
Published: July 2024

AbstractThe alkylation of nucleophiles is among the most fundamental and well‐developed transformations in chemistry. However, to achieve selective alkylation of complex substrates remains a nontrivial task. We report herein a general and selective alkylation method without using strong acids, bases, or metals. In this method, the readily available phosphinites/phosphites, in combination with ethyl acrylate, function as effective alkylating agents. Various nucleophilic groups, including alcohols, phenols, carboxylic acids, imides, and thiols can be alkylated. This method can be applied in the late‐stage alkylation of natural products and pharmaceutical agents, achieving chemo‐ and site‐selective modification of complex substrates. Experimental studies indicate the relative reactivity of a nucleophile depends on its acidity and its steric environment. Mechanistic studies suggest the reaction pathway resembles that of the Arbuzov‐Michalis reaction.
A polyurethane elastomer combining high strength and excellent self‐healing properties for waterproofing coatings
Authors: Liu Zhen , Xu Heng , Fan Zhijie , Zhang Xiandie , Cui Xuxu , Ji Jie , Li Haozhe , Guo Xiaode 
Published: July 2024

AbstractSelf‐healing materials have not been able to solve the problem of the coexistence of mechanical strength and self‐healing function. Despite years of research, high‐strength self‐healing materials still require external factors to accelerate their self‐healing process. For this reason, in this study, two kinds of chain extenders were inserted into the hard segment to design the molecular structure of polyurethane. The introduction of two chain extenders not only provided multiple binding modes for hydrogen bond recombination, but also formed more types of hydrogen bonds. Based on the design, a polyurethane elastomer PUGI‐D3B2 with high strength and excellent self‐healing properties was synthesized. Data such as FTIR and 1H NMR spectra clearly demonstrate the successful synthesis of PUGI‐D3B2. The mechanical strength of PUGI‐D3B2 is 15.34 MPa, and its surface scratches can completely disappear after self‐healing at 60°C for 10 h，and 98.02% of the mechanical strength is restored after 12 h of heal. Therefore, combining the excellent self‐healing properties of PUGI‐D3B2, we prepared a multifunctional superhydrophobic material (SHN‐SiO2/PUGI‐D3B2). It can be used in a wide range of applications such as waterproof coatings, biomedicine and flexible electronics, which provides a new idea for the future direction of multifunctional materials.
Fluorogenic Monitoring of α‐Amylase in Human Urine for Straightforward Diagnosis of Pancreatic Diseases
Authors: Choi Haemin , Kim Seoyun , Park Taemin , Lee Seoung Ho 
Published: July 2024

AbstractIn this study, we developed a sensitive method for monitoring α‐amylase using a fluorogenic approach based on the host‐guest complexation between an amphiphilic pyrenyl derivative (1) and γ‐cyclodextrins (γ‐CDs). The compound 1 self‐assembles into nanofibrils in aqueous solutions. Upon the introduction of γ‐CD, compound 1 forms an inclusion complex with it. This complex then participates in the formation of a 2 : 2 complex with another complex, leading to strong excimer fluorescence. Upon interaction with α‐amylase, γ‐CD undergoes hydrolysis, leading to the regeneration of nanofibrils, which is accompanied by a decrease in excimer fluorescence and an increase in monomeric fluorescence. This ratiometric fluorescence color change enables the sensitive detection of low levels of α‐amylase in human urine, offering a practical approach for early screening of pancreatic‐related diseases.
Additional treatment after primary conservative treatment in patients with chronic subdural hematoma—A retrospective study
Authors: Fakhry Rahman , Dirven Clemens M. F. , Moudrous Walid , Droger S. Mirjam , Asahaad Nabil , de Brabander Christiaan , Lingsma Hester F. , van der Gaag Niels A. , Hertog Heleen M. den , Jacobs Bram , Jellema Korné , Dammers Ruben , Holl Dana C. 
Published: July 2024

AbstractObjectiveChronic subdural hematoma (CSDH) is a common neurological condition and is typically treated with burr hole craniostomy. Nevertheless, conservative treatment may lead to spontaneous hematoma resolution in some patients. This study aims to describe the characteristics of patients who were treated conservatively without the eventual need for additional treatment.MethodsData were retrospectively collected from patients who were primarily treated conservatively in three hospitals in the Netherlands from 2008 to 2018. The Primary outcome was the nonnecessity of additional treatment within 3 months after the initial CSDH diagnosis. We used univariable and multivariable logistic regression analyses to identify factors associated with not receiving additional treatment.ResultsIn this study, 83 patients were included and 61 patients (73%) did not receive additional treatment within 3 months. Upon first presentation, the patients had a Markwalder Grading Scale score (MGS) of 0 (n = 5, 6%), 1 (n = 43, 52%), and 2 (n = 35, 42%). Additional treatment was less often received by patients with smaller hematoma volumes (adjusted odds ratio [aOR] 0.78 per 10 mL; 95% confidence interval [CI] 0.64–0.92). Patients using antithrombotic medication also received less additional treatment, but this association was not significant (aOR 2.02; 95% CI 0.61–6.69).ConclusionsThree quarters of the initially conservatively treated CSDH patients do not receive additional management. Typically, these patients have smaller hematoma volumes. Further, prospective research is needed to distinguish which patients require surgical intervention and in whom primary conservative treatment suffices.
The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models
Authors: Lyu Zhimai , Xiao Guodong , Xie Dingyi , Huang Dandan , Chen Yanjun , Wu Chunmei , Lai Yanwei , Song Zitan , Huang Lijuan , Ming Hui , Jiang Yichen , Wang Jinwei , Chen Rixin , Luo Weifeng 
Published: July 2024

AbstractBackgroundHigh‐frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS.ObjectiveThe current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high‐frequency rTMS) and explore the optimal high‐frequency rTMS on an animal PD model.MethodsFollowing high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid‐induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored.ResultsWe found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain‐derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT‐2) and the suppression of TNF‐α and IL‐1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest.ConclusionsCombined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.
The integration of circular economy and digital transformation as a catalyst for small and medium enterprise innovation
Authors: Arroyabe Marta F. , Arranz Carlos F. A. , de Arroyabe Juan Carlos Fernandez 
Published: July 2024

AbstractThis study examines the integration of digital and circular economy (CE) strategies in small and medium enterprises (SMEs) and their impact on innovation. The research uses data from the Eurobarometer survey conducted by the European Commission, which includes a sample of 16,365 SMEs. Using a combination of regression analysis and machine learning tools, the results indicate that a high degree of digitalisation within SMEs enhances the integration of a CE orientation. However, it is not necessary for SMEs with advanced CE orientations to have high levels of digitalisation. Additionally, the study finds variability in the integration of digital and CE orientations among SMEs, identifying four distinct groups of companies with differing levels of compatibility. Moreover, SMEs that successfully integrate both digital and CE orientations are more likely to innovate, whereas those with poor integration exhibit a lower probability of innovation. These findings offer crucial insights for managers and policymakers aiming to bolster SME innovation, digitalisation and sustainability. The research underscores the need for a balanced integration of digital and CE orientations to enhance innovation and environmental impact in SMEs.
CNS Drug Discovery in Academia: Where Basic Research Meets Innovation
Authors: Gertsch Jürg , Chicca Andrea 
Published: July 2024

AbstractThe involvement of academic research in drug discovery is consistently growing. However, academic projects seldom advance to clinical trials. Here, we assess the landscape of drug discovery within the National Centre of Competence in Research (NCCR) TransCure launched by the Swiss National Science Foundation to foster basic research and early‐stage drug discovery on membrane transporters. This included transporters in central nervous system (CNS) disorders, which represent a huge unmet medical need. While idea championship, sustainable funding, collaborations between disciplines at the interface of academia and industry are important for translational research, Popperian falsifiability, strong intellectual property and a motivated startup team are key elements for innovation. This is exemplified by the NCCR TransCure spin‐off company Synendos Therapeutics, a clinical stage biotech company developing the first selective endocannabinoid reuptake inhibitors (SERIs) as novel treatment for neuropsychiatric disorders. We provide a perspective on the challenges related to entering an uncharted druggable space and bridging the often mentioned “valley of death”. The high attrition rate of drug discovery projects in the CNS field within academia is often due to the lack of meaningful animal models that can provide pharmacological proof‐of‐concept for potentially disruptive technologies at the earliest stages, and the absence of solid intellectual property.
Radical total pelvic exenteration with concomitant right nephrectomy in the management of recurrent endometrioid ovarian adenocarcinoma: A case report and literature review
Authors: Ramachandran Raghavskandhan , Nistor Sabina , Gietzmann William , Symons Nicholas , Soleymani majd Hooman 
Published: July 2024

Key Clinical MessageEndometrioid ovarian adenocarcinoma is a common subtype of epithelial ovarian cancer that can arise on a background of endometriosis. Maximal cytoreductive effort with an aim to remove all macroscopic disease (achieve R0) is the single independent prognostic factor for survival. Complex multidisciplinary surgeries may be required in order to achieve this.