bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Deep Brain Stimulation Sites and Networks for Cervical vs. Generalized Dystonia
Authors: Horn Andreas , Reich Martin , Ewert Siobhan , Li Ningfei , Al-Fatly Bassam , Lange Florian , Roothans Jonas , Oxenford Simon , Horn Isabel , Paschen Steffen , Runge Joachim , Wodarg Fritz , Witt Karsten , Nickl Robert C. , Wittstock Matthias , Schneider Gerd-Helge , Mahlknecht Philipp , Poewe Werner , Eisner Wilhelm , Helmers Ann-Kristin , Matthies Cordula , Krauss Joachim K. , Deuschl Günther , Volkmann Jens , Kühn Andrea 
Published: July 2021

AbstractDystonia is a debilitating disease with few conservative treatment options but many types of isolated dystonia can be effectively treated using deep brain stimulation (DBS) to the internal pallidum.While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations between optimal stimulation sites and potential network effects in the two types of dystonia have not been carried out.Here, we retrospectively investigate clinical results following DBS for cervical and generalized dystonia in a multi-center cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce a novel approach to map optimal stimulation sites to anatomical space. Second, we analyse stimulation in context of a detailed pathway model of the subcortex to investigate the modulation of which tracts accounts for optimal clinical improvements. Third, we investigate stimulation in context of a broad-lense whole-brain functional connectome to illustrate potential multisynaptic network effects. Finally, we construct a joint model using local, tract- and network-based effects to explain variance in clinical outcomes in cervical and generalized dystonia.Our results show marked differences in optimal stimulation sites that map to the somatotopic structure of the internal pallidum. We further highlight that modulation of the pallidofugal main axis of the basal ganglia may be optimal for treatment of cervical dystonia, while pallidothalamic bundles account for effects in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in form of connectivity to cerebellum and somatomotor cortex.Our results suggest a multi-level model that could account for effectivity of treatment in cervical and generalized dystonia and could potentially help guide DBS programming and surgery, in the future.
Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes
Authors: Poppelaars Felix , da Costa Mariana Gaya , Faria Bernardo , Eskandari Siawosh K. , Seelen Marc A. , Damman Jeffrey 
Published: July 2021

AbstractIntroductionKidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-α) gene (TNF) polymorphisms on kidney graft survival.MethodsWe performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function (PNF) and death-censored kidney allograft survival in 1,271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands.ResultsThe G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of PNF (odds ratio: 2.05; 95%-CI: 1.06-3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P < 0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05-2.19, P = 0.028).ConclusionKidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-α blockade in improving kidney transplantation outcomes.
Prevalence and Time of Diagnosis of Endometriosis across Racial and Ethnic Groups in the US
Authors: Li Rui , Kreher Donna A , Gubbels Ashley L , Benjamin Amy R 
Published: July 2021

AbstractBackgroundEndometriosis is associated with substantial adverse health and psychosocial consequences. However, the prevalence of endometriosis across different racial and ethnic groups in the US has not been established and to what extent the difference in prevalence might be associated with systemic barriers to receiving the diagnosis is unknown. We aimed to estimate the prevalence of endometriosis across different racial and ethnic groups and examine the association between race/ethnicity and the time of diagnosisMethodsUsing cross-sectional data from the National Health and Nutrition Examination Survey 1999-2006, we estimated race/ethnicity-specific prevalence of self-reported diagnosis of endometriosis among 5,557 women aged 20-54 years. Multivariable generalized linear regression model examined the association between race/ethnicity and the age of endometriosis diagnosis, accounting for socioeconomic indicators, health insurance, lifestyle and reproductive characteristics.ResultsEndometriosis was prevalent in 9.0% overall, 11.1% among non-Hispanic white, 5.8% among non-Hispanic black, 2.7% among Hispanic, and 6.4% among the other racial and ethnic groups combined. The mean age of endometriosis diagnosis was 29.0 years (range 13-52). Compared with non-Hispanic white, non-Hispanic black women were diagnosed on average at 2.6 years older (95% confidence interval [CI], 0.5-4.6), Hispanic women 3.8 years older (95% CI 1.5-6.2), and women in the other group 1.0 years younger (95% CI, -4.6 to 2.5).ConclusionsPrevalence of endometriosis varied across different racial and ethnic groups Among women with a diagnosis of endometriosis, black and Hispanic women were diagnosed at older ages than non-Hispanic white women. Future research is needed to determine whether such age disparity in endometriosis diagnosis persists.
Development and validation of a multimodal neuroimaging biomarker for electroconvulsive therapy outcome in depression: a multicenter machine learning analysis
Authors: Bruin Willem B. , Oltedal Leif , Bartsch Hauke , Abbott Christopher C. , Argyelan Miklos , Barbour Tracy , Camprodon Joan A. , Chowdhury Samadrita , Espinoza Randall , Mulders Peter C. R. , Narr Katherine L. , Oudega Mardien L. , Rhebergen Didi , ten Doesschate Freek , Tendolkar Indira , van Eijndhoven Philip , van Exel Eric , van Verseveld Mike , Wade Benjamin , van Waarde Jeroen , Zhutovsky Paul , Dols Annemiek , van Wingen Guido A. 
Published: July 2021

AbstractBackgroundElectroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, mono-center studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers.ObjectiveTo develop and validate neuroimaging biomarkers for ECT outcome in a multi-center setting.MethodsMultimodal data (i.e., clinical, sMRI and resting-state fMRI) was collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluated which data modalities or combinations thereof could provide the best predictions for treatment response (≥50% symptom reduction) or remission (HAM-D score ≤7) using a support vector machine classifier.ResultsRemission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82-0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers, and remained acceptable when validated using leave-one-site-out cross-validation (0.70-0.73 AUC).ConclusionsThese results show that multimodal neuroimaging data is able to provide good prediction of remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. This suggests that these biomarkers are robust, indicating that future development of a clinical decision support tool applying these biomarkers may be feasible.
Photosensitized Electrospun Nanofibrous Filters for Capturing and Killing Airborne Coronaviruses under Visible Light Irradiation
Authors: Shen Hongchen , Zhou Zhe , Wang Haihuan , Zhang Mengyang , Han Minghao , Shen Yun , Shuai Danmeng 
Published: July 2021

AbstractTo address the challenge of the airborne transmission of SARS-CoV-2, photosensitized electrospun nanofibrous membranes were fabricated to effectively capture and inactivate coronavirus aerosols. With an ultrafine fiber diameter (∼ 200 nm) and a small pore size (∼ 1.5 µm), the optimized membranes caught 99.2% of the aerosols of the murine hepatitis virus A59 (MHV-A59), a coronavirus surrogate for SARS-CoV-2. In addition, rose bengal was used as the photosensitizer for the membranes because of its excellent reactivity in generating virucidal singlet oxygen, and the membranes rapidly inactivated 98.9% of MHV-A59 in virus-laden droplets only after 15 min irradiation of simulated reading light. Singlet oxygen damaged the virus genome and impaired virus binding to host cells, which elucidated the mechanism of disinfection at a molecular level. Membrane robustness was also evaluated, and no efficiency reduction for filtering MHV-A59 aerosols was observed after the membranes being exposed to both indoor light and sunlight for days. Nevertheless, sunlight exposure photobleached the membranes, reduced singlet oxygen production, and compromised the performance of disinfecting MHV-A59 in droplets. In contrast, the membranes after simulated indoor light exposure maintained their excellent disinfection performance. In summary, photosensitized electrospun nanofibrous membranes have been developed to capture and kill airborne environmental pathogens under ambient conditions, and they hold promise for broad applications as personal protective equipment and indoor air filters.SynopsisPhotosensitized electrospun nanofibrous filters with excellent capture-and-kill performance against coronaviruses were designed and implemented to prevent the airborne transmission of COVID-19.Table of Contents
Accuracy verification of low-cost CO2 concentration measuring devices for general use as a countermeasure against COVID-19
Authors: Ishigaki Yo , Enoki Koji , Yokogawa Shinji 
Published: July 2021

AbstractWithin the context of the COVID-19 pandemic, CO2 sensors that measure ventilation conditions and thereby reduce the risk of airborne infection, are gaining increasing attention. We investigated and verified the accuracy of 12 relatively low-cost sensor models that retail for less than $45 and are advertised as infection control measures on a major e-commerce site. Our results indicate that 25% of the tested sensors can be used to identify trends in CO2 concentration, if correctly calibrated. However, 67% of sensors did not respond to the presence of CO2, which suggests that a type of pseudo-technique is used to display the CO2 concentration. We recommend that these sensors are not suitable for infection prevention purposes. We also found that all 67% of the sensors that did not respond to CO2 responded strongly to alcohol. Owing to the widespread use of alcohol in preventing the spread of infectious diseases, sensors that react to alcohol can display inaccurate values, resulting in inappropriate ventilation behavior. Therefore, we strongly recommended that these sensors not be used. Based on our results, we offer practical recommendations to the average consumer, who does not have special measuring equipment, on how to identify inaccurate CO2 sensors.
Epigenetic Divergence during Early Stages of Speciation in an African Crater Lake Cichlid Fish
Authors: Vernaz Grégoire , Hudson Alan G. , Emília Santos M. , Fischer Bettina , Carruthers Madeleine , Shechonge Asilatu H. , Gabagambi Nestory P. , Tyers Alexandra M. , Ngatunga Benjamin P. , Malinsky Milan , Durbin Richard , Turner George F. , Genner Martin J. , Miska Eric A. 
Published: July 2021

AbstractEpigenetic variation can alter transcription and promote phenotypic divergence between populations facing different environmental challenges. Here we assess the epigenetic basis of diversification during the early stages of speciation. We focus on the extent and functional relevance of DNA methylome divergence between two Astatotilapia calliptera ecomorphs in crater Lake Masoko, southern Tanzania. We report extensive genome-wide methylome divergence between populations linked to key biological processes, including transcriptional activity of ecologically-relevant genes. These include genes involved in steroid metabolism, haemoglobin composition and erythropoiesis, consistent with divergent habitat occupancy of the ecomorphs. Using a common garden experiment, we found that global methylation profiles are rapidly remodelled across generations, but ecomorph-specific differences can be inherited. Collectively, our study suggests an epigenetic contribution to early stages of vertebrate speciation.One sentence summaryInheritance and plasticity of epigenetic divergence characterise early stages of speciation in an incipient cichlid species of an African crater lake.
Mice with High FGF21 Serum Levels Had a Reduced Preference for Morphine and an Attenuated Development of Acute Antinociceptive Tolerance and Physical Dependence
Authors: Dorval Louben , Knapp Brian I. , Majekodunmi Olufolake A. , Eliseeva Sophia , Bidlack Jean M. 
Published: July 2021

ABSTRACTBecause of increased opioid misuse, there is a need to identify new targets for minimizing opioid tolerance, and physical and psychological dependence. Previous studies showed that fibroblast growth factor 21 (FGF21) decreased alcohol and sweet preference in mice. In this study, FGF21-transgenic (FGF21-Tg) mice, expressing high FGF21 serum levels, and wildtype (WT) C57BL/6J littermates were treated with morphine and saline to determine if differences exist in their physiological and behavioral responses to opioids. FGF21-Tg mice displayed reduced preference for morphine in the conditioned place preference assay compared to WT littermates. Similarly, FGF21-Tg mice had an attenuation of the magnitude and rate of acute morphine antinociceptive tolerance development, and acute and chronic morphine physical dependence, but exhibited no change in chronic morphine antinociceptive tolerance. The ED50 values for morphine-induced antinociception in the 55°C hot plate and the 55°C warm-water tail withdrawal assays were similar in both strains of mice. Likewise, FGF21-Tg and WT littermates had comparable responses to morphine-induced respiratory depression. Overall, FGF21-Tg mice had a decrease in the development of acute analgesic tolerance, and the development of physical dependence, and morphine preference. FGF21 and its receptor have therapeutic potential for reducing opioid withdrawal symptoms and craving, and augmenting opioid therapeutics for acute pain patients to minimize tolerance development.
Activation of M1muscarinic receptors reduce pathology and slow progression of neurodegenerative disease
Authors: Dwomoh Louis , Rossi Mario , Scarpa Miriam , Khajehali Elham , Molloy Colin , Herzyk Pawel , Mistry Shailesh N. , Bottrill Andrew R. , Sexton Patrick M. , Christopoulos Arthur , Conn P. Jeffery , Lindsley Craig W. , Bradley Sophie J. , Tobin Andrew B. 
Published: July 2021

ABSTRACTThe most prevalent types of dementias, including Alzheimer’s disease, are those that are propagated via the spread of“prion-like”misfolded proteins. Despite considerable effort no treatments are available to slow or stop the progression of these dementias. Here we investigate the possibility that activation of the M1-muscarinic receptor (M1-receptor), which is highly expressed in the brain and that shows pro-cognitive properties, might present a novel disease modifying target. We demonstrate that the progression of murine prion disease, which we show here displays many of the pathological, behavioural and biochemical hallmarks of human neurodegenerative disease, is slowed and normal behaviour maintained by the activation of the M1-receptor with a highly tolerated positive allosteric modulator (VU846). This correlates with a reduction in both neuroinflammation and indicators of mitochondrial dysregulation, as well as a normalisation in the expression of markers associated with neurodegeneration and Alzheimer’s disease. Furthermore, VU846 preserves expression of synaptic proteins and post-synaptic signalling components that are altered in disease. We conclude that allosteric regulation of M1-receptors has the potential to reduce the severity of neurodegenerative diseases caused by theprion-likepropagation of misfolded protein in a manner that extends life span and maintains normal behaviour.
Identification and characterization of novel mutants of Nsp13 protein among Indian SARS-CoV-2 isolates
Authors: Kumari Deepa , Kumari Namrata , Kumar Sudhir , Sinha Prabhat Kumar , Shahi Shivendra Kumar , Biswas Nihar Ranjan , Kumar Abhay 
Published: July 2021

ABSTRACTSARS-CoV-2, the causative agent of COVID-19 has mutated rapidly which enabled them to adapt and evade the immune system of the host. Emerging SARS-CoV-2 variants with crucial mutations pose a global challenge in context of therapeutic drugs and vaccines being developed globally. There are currently no specific therapeutics or vaccines available to combat SARS-CoV-2 devastation. In view of this, the current study aimed to identify and characterize the mutations found in the Nsp13 of SARS-CoV-2 in Indian isolates. Non-structural protein, Nsp13 protein sequences from Indian isolates were analyzed by comparing with the first reported Severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) protein sequence from Wuhan, China. Out of 825 Nsp13 protein sequences, a total of 38 mutations were observed among Indian isolates. Our data show that mutations in Nsp13 at various positions (H164Y, A237T, T214I, C309Y, S236I, P419S, V305E, G54S, H290Y, P53S, A308Y, and A308Y) have a significant impact on the protein’s stability and flexibility. Also, the impact of Nsp13 mutations on the protein function were predicted based on PROVEAN score that includes 15 mutants as neutral and 23 mutants as deleterious effect. Furthermore, B-cell epitopes contributed by Nsp13 were identified using various predictive immunoinformatic tools. Immunological Parameters of Nsp13 such as antigenicity, allergenicity and toxicity were evaluated to predict the potential B-cell epitopes. The predicted peptide sequences were correlated with the observed mutants. Our predicted data showed that there are seven high rank linear epitopes as well as 18 discontinuous B-cell epitopes based on immunoinformatic tools. Moreover, it was observed that out of total 38 identified mutations among Indian SARS-CoV-2 Nsp13 protein, four mutant residues at position 142 (E142), 245 (H245), 247 (V247) and 419 (P419) are localised in the predicted B cell epitopic region. Altogether, the results of the present in-silico study might help to understand the impact of the identified mutations in Nsp13 protein on its stability, flexibility and function.
AtpΘ is an inhibitor of F0F1 ATP synthase to arrest ATP hydrolysis during low-energy conditions in cyanobacteria
Authors: Song Kuo , Baumgartner Desirée , Hagemann Martin , Muro-Pastor Alicia M. , Maaß Sandra , Becher Dörte , Hess Wolfgang R. 
Published: July 2021

SummaryBiological processes in all living cells are powered by ATP, a nearly universal molecule of energy transfer. ATP synthases produce ATP utilizing proton gradients that are usually generated by either respiration or photosynthesis. However, cyanobacteria are unique in combining photosynthetic and respiratory electron transport chains in the same membrane system, the thylakoids. How cyanobacteria prevent the futile reverse operation of ATP synthase under unfavorable conditions pumping protons while hydrolyzing ATP is mostly unclear. Here, we provide evidence that the small protein AtpΘ, which is widely conserved in cyanobacteria, is mainly fulfilling this task. The expression of AtpΘ becomes induced under conditions such as darkness or heat shock, which can lead to a weakening of the proton gradient. Translational fusions of AtpΘ to the green fluorescent protein revealed targeting to the thylakoid membrane. Immunoprecipitation assays followed by mass spectrometry and far Western blots identified subunits of ATP synthase as interacting partners of AtpΘ. ATP hydrolysis assays with isolated membrane fractions as well as purified ATP synthase complexes demonstrated that AtpΘ inhibits ATPase activity in a dose-dependent manner similar to the F0F1-ATP synthase inhibitor N,N-dicyclohexylcarbodimide. The results show that, even in a well-investigated process, crucial new players can be discovered if small proteins are taken into consideration and indicate that ATP synthase activity can be controlled in surprisingly different ways.
Lipid flippase dysfunction as a novel therapeutic target for endosomal anomalies in Alzheimer’s disease
Authors: Kaneshiro Nanaka , Komai Masato , Imaoka Ryosuke , Ikeda Atsuya , Kamikubo Yuji , Hashimoto Tadafumi , Iwatsubo Takeshi , Sakurai Takashi , Uehara Takashi , Takasugi Nobumasa 
Published: July 2021

Abstractβ-amyloid precursor protein (APP) and their metabolites are deeply involved in the development of Alzheimer’s disease (AD). Upon the upregulation of β-site APP cleaving enzyme 1 (BACE1), its product, the β-carboxyl-terminal fragment of APP (βCTF), is accumulated in the early stage of sporadic AD brains. βCTF accumulation is currently considered the trigger for endosomal anomalies to form enlarged endosomes, one of the earliest pathologies in AD. However, the details of the underlying mechanism remain largely unclear. In this study, using BACE1 stably-overexpressing cells, we describe that lipid flippase subcomponent TMEM30A interacts with accumulated βCTF. Among the lipid flippases in endosomes, those composed of TMEM30A and active subcomponent ATP8A1 transports phospholipid, phosphatidylserine (PS), to the cytosolic side of the endosomes. The lipid flippase activity and cytosolic PS distribution are critical for membrane fission and vesicle transport. Intriguingly, accumulated βCTF in model cells impaired lipid flippase physiological formation and activity, along with endosome enlargement. Moreover, in the brains of AD model mice before the amyloid-β (Aβ) deposition, the TMEM30A/βCTF complex formation occurred, followed by lipid flippase dysfunction. Importantly, our novel Aβ/βCTF interacting TMEM30A-derived peptide “T-RAP” improved endosome enlargement and reduced βCTF levels. These T-RAP effects could result from the recovery of lipid flippase activity. Therefore, we propose lipid flippase dysfunction as a key pathogenic event and a novel therapeutic target for AD.