bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isotopologue pattern based data mining for selenium species from HILIC–ESI–Orbitrap–MS-derived spectra
Authors: Bierla Katarzyna , Godin Simon , Ladányi Márta , Dernovics Mihály , Szpunar Joanna 
Published: December 2022

Abstract
Automated and specific picking of selenium-containing molecular entities has not been an obvious option for software tools associated with electrospray high-resolution mass spectrometry (MS). In our study, a comprehensive pattern matching approach based on intra-isotopologue distance and isotopologue ratio data was critically evaluated in terms of reproducibility and selenium isotope selection on three samples, including selenized Torula yeast and the selenium hyperaccumulator plant Cardamine violifolia. Hydrophilic interaction liquid chromatography was applied to provide a one-step separation for water soluble metabolites to put an end to the need for either orthogonal setups or poor retention on reversed phase chromatography. Assistance from inductively coupled plasma–MS was taken only for chromatographic verification purposes, and the involvement of absolute mass defect (MD) data in selenometabolite-specific screening was assessed by multivariate statistical tools. High focus was placed on screening efficiency and on the validation of discovered selenized molecules to avoid reporting of artefacts. From the &gt;1000 molecular entries detected, selenium-containing molecules were picked up with a recovery rate of &gt;88% and a false positive rate of &lt;10%. Isotop(ologu)e pairs of 78Se–80Se and 80Se–82Se proved to be the most performant in the detection. On the basis of accurate mass information and hypothetical deamination processes, elemental composition could be proposed for 72 species out of the 75 selenium species encountered without taking into account selenocompound databases. Absolute MD data were used to significantly differentiate a potentially sample-specific subgroup of false positive molecular entities from non-selenized and selenized entities.
Long-term peridialytic blood pressure changes are related to mortality
Authors: de Roij van Zuijdewijn Camiel L M , Rootjes Paul A , Nubé Menso J , Bots Michiel L , Canaud Bernard , Blankestijn Peter J , van Ittersum Frans J , Maduell Francisco , Morena Marion , Peters Sanne A E , Davenport Andrew , Vernooij Robin W M , Grooteman Muriel P C ,   the HDF Pooling Project investigators, Bots Michiel L , Blankestijn Peter J , Canaud Bernard , Davenport Andrew , Grooteman Muriel P C , Nubé Menso J , Peters Sanne A E , Morena Marion , Maduell Francisco , Torres Ferran , Ok Ercan , Asci Gulay , Locatelli Francesco 
Published: December 2022

ABSTRACT

Background
In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated.

Methods
To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied.

Results
During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P &lt; .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality.

Conclusion
Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.
Rare but persistent asexual reproduction explains the success of planktonic foraminifera in polar oceans
Authors: Meilland Julie , Ezat Mohamed M , Westgård Adele , Manno Clara , Morard Raphaël , Siccha Michael , Kucera Michal 
Published: December 2022

Abstract
The reproductive strategy of planktonic foraminifera, key pelagic calcifiers, has long remained elusive, hampering efforts to understand and model their population dynamics. This is particularly critical in polar oceans where their success relies on rapid population growth after the polar night. Here, we provide field and laboratory observations constraining the reproductive cycle of the dominant polar species Neogloboquadrina pachyderma in Antarctic and Arctic waters. We observe that asexual reproduction is a rare but persistent element of the reproductive strategy and that it is reflected in a dimorphism in proloculus and in the ratio of shell size versus the number of chambers between sexually and asexually produced individuals. This dimorphism in natural populations reveals that asexual reproduction supplies more than 75% of adult individuals. This indicates a multigenerational reproduction strategy, where the majority of the population releases gametes to facilitate recombination, while a minority persistently reproduces asexually, allowing rapid population growth as a prerequisite for success in the polar oceans.
Calanus helgolandicus - more than a guest in the north?
Authors: Schultz Mads , Choquet Marvin , Tverberg Vigdis , Hoarau Galice 
Published: December 2022

AbstractMolecular identification of Calanus helgolandicus has revealed a more northern distribution for this boreal species than previously reported. We investigated an Arctic fjord to determine if local reproduction is taking place. Combining time series data from depth stratified sampling with molecular tools for species identification, we found C. helgolandicus from all stages throughout the year including males and females as well as a nauplius. These findings constitute strong evidence that C. helgolandicus is reproducing north of the Arctic Circle and their role in the ecosystem should be investigated further.
Information maximization explains state-dependent synaptic plasticity and memory reorganization during non-rapid eye movement sleep
Authors: Yoshida Kensuke , Toyoizumi Taro 
Published: December 2022

Abstract
Slow waves during the non-rapid eye movement (NREM) sleep reflect the alternating up and down states of cortical neurons; global and local slow waves promote memory consolidation and forgetting, respectively. Furthermore, distinct spike-timing-dependent plasticity (STDP) operates in these up and down states. The contribution of different plasticity rules to neural information coding and memory reorganization remains unknown. Here, we show that optimal synaptic plasticity for information maximization in a cortical neuron model provides a unified explanation for these phenomena. The model indicates that the optimal synaptic plasticity is biased toward depression as the baseline firing rate increases. This property explains the distinct STDP observed in the up and down states. Furthermore, it explains how global and local slow waves predominantly potentiate and depress synapses, respectively, if the background firing rate of excitatory neurons declines with the spatial scale of waves as the model predicts. The model provides a unifying account of the role of NREM sleep, bridging neural information coding, synaptic plasticity, and memory reorganization.
Detection of the 4.4-MeV gamma rays from 16O(ν, ν′)16O(12.97 MeV, 2−) with a water Cherenkov detector in supernova neutrino bursts
Authors: Sakuda Makoto , Suzuki Toshio , Reen Mandeep Singh , Nakazato Ken’ichiro , Suzuki Hideyuki 
Published: December 2022

Abstract
We first discuss and determine the isospin mixing of the two 2− states (12.53 MeV and 12.97 MeV) of the16O nucleus using inelastic electron scattering data. We then evaluate the cross section of 4.4-MeV γ rays produced in the neutrino neutral-current (NC) reaction 16O(ν, ν′)16O(12.97 MeV, 2−) in a water Cherenkov detector at a low energy, below 100 MeV. The detection of γ rays for Eγ &gt; 5 MeV from the NC reaction 16O(ν, ν′)16O(Ex &gt; 16 MeV, T = 1) with a water Cherenkov detector in supernova neutrino bursts has been proposed and discussed by several authors previously. In this article, we discuss a new NC reaction channel from 16O(12.97 MeV, 2−) producing a 4.4-MeV γ ray, the cross section of which is more robust and even larger at low energy (Eν &lt; 25 MeV) than the NC cross section from 16O(Ex &gt; 16 MeV, T = 1). We also evaluate the number of such events induced by neutrinos from supernova explosion which can be observed by the Super-Kamiokande, an Earth-based 32-kton water Cherenkov detector.
Outcomes of LGBTQ culturally sensitive training among civilian and military healthcare personnel
Authors: Oblea Pedro N , Bathan Nicole Q , Gaa Christyn A , Lustik Michael B , Tartavoulle Todd M , Nguyen-Wu Elizabeth D , Siaki Leilani A 
Published: December 2022

Abstract

Background
Lesbian, gay, bisexual, transgender, or queer (LGBTQ) military servicemembers are at higher risk of developing health problems compared to heterosexual peers. To improve outcomes and address negative attitudes, previous literature has recommended education of healthcare personnel. The purpose of our study was to evaluate the knowledge and skill outcomes of an LGBTQ cultural sensitivity training program.

Methods
We used a pretest/posttest design. Participants completed the Ally Identity Measure (AIM) to assess three subscales: knowledge and skills, openness and support, and oppression awareness. Participants included both military and civilian healthcare personnel from multiple disciplines. Descriptive statistics and pairwise analyses were used.

Results
A total of 101 participants answered both pretest and posttest. Across all AIM subscales, posttest scores demonstrated statistically significant (P &lt; 0.001) increases from mean pretest scores. Completion rates for the pretest and posttest were 99% and 93%, respectively. The majority of participants were female (75%) and non-Hispanic (87%), composed of Caucasians (39%) and Asians (33%). Over one-third (39%) of participants were aged 30–39. Fifty percent were active-duty military and more than half (58%) of all participants did not have prior training in LGBTQ patient care. Statistically significant differences were found between the pretest and posttest scores for the knowledge and skills subscale (M = 2.64–3.70). The most significant increases were observed in Item 12 and Item 15 (M = 2.72–3.70) regarding awareness of theories and skill development to provide proper support, respectively.

Conclusion
These significant findings contribute to the currently limited research exploring LGBTQ cultural sensitivity training in both civilian and military settings. To our knowledge, this is the first time a cultural sensitivity training of this depth has been provided to active-duty servicemembers. Further research and development of similar educational programs integrating interactive participation can potentially aid in the delivery of improved care and military readiness for all servicemembers.
Location, location, location: does providing public health services from community pharmacies contribute to tackling health inequalities?
Authors: Evans Andrew , Mantzourani Efi , Gillespie David , Hughes Louise , Sharpe Georgia , Yip Nicola 
Published: December 2022

Abstract

Background
Community pharmacies have long been advocated as an accessible source of advice on health improvement in communities. This cross-sectional study explored the association between provision of pharmacy public health services and factors that might influence the extent to which pharmacies contribute to tackling inequalities.

Methods
Publically available data were used to explore the association between pharmacy public health service provision and pharmacy characteristics (socioeconomic deprivation, urbanity, opening hours and workload). Regression models were fitted to the number of service consultations. The association between the number of services provided and the mean number of consultations across each service was investigated using regression models.

Results
Pharmacies showed a propensity for being situated in areas of higher socioeconomic deprivation. There was no association between socioeconomic deprivation and number of service consultations a pharmacy provided. Clustering of pharmacies in less affluent areas led to over half of all public health service consultations being in the two most deprived quintiles.

Conclusions
Providing healthcare services from pharmacies in more deprived areas does not mean the public use them or that pharmacies will prioritize their delivery. The higher prevalence of pharmacies in disadvantaged communities is an important factor in ensuring pharmacy services support reducing inequalities.
The EU financial collateral directive: the distinguishing features of a security financial collateral arrangement?
Authors: Ezike Obiora 
Published: December 2022

Abstract
The first part of this article considers whether a system-neutral meaning of a title transfer financial collateral arrangement (TTFSA) can be identified in the EU Collateral Directive. This part looks at a similar issue—it considers whether system-neutral meaning of a security financial collateral arrangement (SFCA) can be identified in the Financial Collateral Arrangement Directive. It is argued that the definition of a SFCA in the Directive is based on the assumption that there is a specific organizing principle or concept that makes it easy to clearly identify, and demarcate, SFCAs from other types of security arrangements (particularly TTFCAs). While this assumption fits well within the model of Civil law systems, which may have a clear concept of ‘security right’, it does not fit in well within the common law. The arguments in this article call for a careful approach in the system-neutral definition of a SFCA in the Directive.
Learning the Drug-Target Interaction Lexicon
Authors: Singh Rohit , Sledzieski Samuel , Cowen Lenore , Berger Bonnie 
Published: December 2022

Sequence-based prediction of drug-target interactions has the potential to accelerate drug discovery by complementing experimental screens. Such computational prediction needs to be generalizable and scalable while remaining sensitive to subtle variations in the inputs. However, current computational techniques fail to simultaneously meet these goals, often sacrificing performance on one to achieve the others. We develop a deep learning model, ConPLex, successfully leveraging the advances in pre-trained protein language models (“PLex”) and employing a novel protein-anchored contrastive co-embedding (“Con”) to outperform state-of-the-art approaches. ConPLex achieves high accuracy, broad adaptivity to unseen data, and specificity against decoy compounds. It makes predictions of binding based on the distance between learned representations, enabling predictions at the scale of massive compound libraries and the human proteome. Furthermore, ConPLex is interpretable, which enables us to visualize the drug-target lexicon and use embeddings to characterize the function of human cell-surface proteins. We anticipate ConPLex will facilitate novel drug discovery by making highly sensitive and interpretable in-silico drug screening feasible at genome scale. Con-PLex is available open-source athttps://github.com/samsledje/ConPLex.Significance StatementIn time and money, one of the most expensive steps of the drug discovery pipeline is the experimental screening of small molecules to see which will bind to a protein target of interest. Therefore, accurate high-throughput computational prediction of drug-target interactions would unlock significant value, guiding and prioritizing promising candidates for experimental screening. We introduce ConPLex, a machine learning method for predicting drug-target binding which achieves state-of-the-art accuracy on many types of targets by using a pre-trained protein language model. The approach co-locates the proteins and the potential drug molecules in a shared feature space while learning to contrast true drugs from similar non-binding “decoy” molecules. ConPLex is extremely fast, which allows it to rapidly shortlist candidates for deeper investigation.
Plasma protein biomarkers predict both the development of persistent autoantibodies and type 1 diabetes 6 months prior to the onset of autoimmunity: the TEDDY Study
Authors: Nakayasu Ernesto S. , Bramer Lisa M. , Ansong Charles , Schepmoes Athena A. , Fillmore Thomas L. , Gritsenko Marina A. , Clauss Therese R. , Gao Yuqian , Piehowski Paul D. , Stanfill Bryan A. , Engel Dave W. , Orton Daniel J. , Moore Ronald J. , Qian Wei-Jun , Sechi Salvatore , Frohnert Brigitte I. , Toppari Jorma , Ziegler Anette-G. , Lernmark Åke , Hagopian William , Akolkar Beena , Smith Richard D. , Rewers Marian J. , Webb-Robertson Bobbie-Jo M. , Metz Thomas O. 
Published: December 2022

AbstractType 1 diabetes (T1D) results from an autoimmune destruction of pancreatic β cells. A significant gap in understanding the disease cause is the lack of predictive biomarkers for each of its developmental stages. Here, we conducted a blinded, two-phase case-control plasma proteomics analysis of children enrolled in the TEDDY study to identify biomarkers predictive of autoimmunity and T1D development. First, we performed untargeted proteomics analyses of 2,252 samples from 184 individuals and identified 376 regulated proteins. Complement/coagulation, inflammatory signaling and metabolic proteins were regulated even prior to autoimmunity onset. Extracellular matrix proteins and antigen presentation were differentially regulated in individuals with autoimmunity who progressed to T1D versus those who maintained normoglycemia. We then performed targeted proteomics measurements of 167 proteins in 6,426 samples from 990 individuals and validated 83 biomarkers. A machine learning analysis predicted both the development of persistent autoantibodies and T1D onset 6 months before autoimmunity initiation, with an area under the receiver operating characteristic curve of 0.871 and 0.918, respectively. Our study identified and validated biomarkers highlighting pathways affected in different stages of T1D development.
Composition efficacy of Unsaturated Arachidonic acid, Diterpenoids, Malvin (C29H35ClO17), and Bergenin to neutralise venom from different venomous snake species
Authors: Al-Tobi Lujaina N. H. , Albusaidi Juma.Z.K , Ajabri Ali.A , Idris Mohammed A. , Hasson Sidgi S. A A. 
Published: December 2022

AbstractSnakebite envenomation is a serious problem in tropical and subtropical countries. Antivenom is the only treatment used to treat snake envenomation, however it is unable to neutralise local haemorrhage. Therefore, this study’s aim is to evaluate the efficacy ofP. dulceleaf extract to neutralise local haemorrhage induced by three clinically important snake species,B. jararaca, C. atroxandE. carinatus. Moreover, to determine the active components which are responsible for this activity. The plant leaves were extracted using different solvents, however, only E/e extract showed the best neutralizing capacity. The increasing doses, DF-1:2; 1:4, of E/e extract allowed better neutralizing ability s.c. In contrast, the oral/ i.p. acute toxicity test revealed that the optimal doses for the administration of E/e were 1 and 8 mg/kg. In addition to that, E/e was tested for its anti-lathality of LD50usingB. jararacavenom (1.1mg/kg) i.p., where the higher doses of 16 and 24 mg/kg killed 75% of BALB/C mice. Consequently, the different components of E/e extract were isolated with HPLC. The different components were grouped and tested to uncover the active ones. The results revealed that only three fractions were active, Frc11, Frc13, and Frc14. The active fractions showed a disparity in neutralizing the individual venoms, however, the best neutralising capacity was scored for Frc11. When the same fractions were pooled together, they showed a complete neutralizing ability against individual venoms as well as the pooled venoms. That was confirmed with the anti-gelatinase activity test, where pooled fraction inhibited the SVMP enzyme which is responsible for gelatinase activity. The phytochemical characterisation showed that the active fractions consist mainly of secondary metabolites such as tannins and polyphenols. MALDI-TOF MS confirmed the presence of secondary metabolites in the active fractions. The same fractions were tested for their anti-lethal activity using the pooled venoms (LD100), the results were statistically not significant, as all mice died including the positive controls. Nevertheless, the active fractions showed a noticeable increasing in survival time period especially Frc13 with an average survival time of 37 minutes. The positive control, IAV, scored the longest survival period with a gap of 11 minutes from Frc13.
A framework for deriving analytic long-term behavior of biochemical reaction networks
Authors: Hernandez Bryan S. , Lubenia Patrick Vincent N. , Johnston Matthew D. , Kim Jae Kyoung 
Published: December 2022

AbstractThe long-term behaviors of biochemical systems are described by their steady states. Deriving these states directly for complex networks arising from real-world applications, however, is often challenging. Recent work has consequently focused on network-based approaches. Specifically, biochemical reaction networks are transformed into weakly reversible and deficiency zero networks, which allows the derivation of their analytic steady states. Identifying this transformation, however, can be challenging for large and complex networks. In this paper, we address this difficulty by breaking the complex network into smaller independent subnetworks and then transforming the subnetworks to derive the analytic steady states of each subnetwork. We show that stitching these solutions together leads to the the analytic steady states of the original network. To facilitate this process, we develop a user-friendly and publicly available package, COMPILES (COMPutIng anaLytic stEady States). With COMPILES, we can easily test the presence of bistability of a CRISPRi toggle switch model, which was previously investigated via tremendous number of numerical simulations and within a limited range of parameters. Furthermore, COMPILES can be used to identify absolute concentration robustness (ACR), the property of a system that maintains the concentration of particular species at a steady state regardless of any initial concentrations. Specifically, our approach completely identifies all the species with and without ACR in a complex insulin model. Our method provides an effective approach to analyzing and understanding complex biochemical systems.Author summarySteady states describe the long-term behaviors of biochemical systems, which are typically based on ordinary differential equations. To derive a steady state analytically, significant attention has been given in recent years to network-based approaches. While this approach allows a steady state to be derived as long as a network has a special structure, complex and large networks rarely have this structural property. We address this difficulty by breaking the network into smaller and more manageable independent subnetworks, and then use the network-based approach to derive the analytic steady state of each subnetwork. Stitching these solutions together allows us to derive the analytic steady state of the original network. To facilitate this process, we develop a user-friendly and publicly available package, COMPILES. COMPILES identifies critical biochemical properties such as the presence of bistability in a genetic toggle switch model and absolute concentration robustness in a complex insulin signaling pathway model.