bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of Sexual Assault Services in a Clinic Setting
Authors: Pitcher Michelle , Connerton Charlotte , Bonham Elizabeth 
Published: November 2021

ABSTRACT
Sexual assault services cost Americans more than $420,000,000 annually for medical and mental health services. Personal costs include lost wages, lost quality of life, and victim assistance. Public costs include police work, legal adjudication, and sanctioning (penalties). In 2014, an estimated 284,350 adult women were sexually assaulted in the United States. Sexual assault is significantly underreported by those who are assaulted. Upon determination that sexual assault services in a clinic setting were nonexistent, services for sexual assault were developed and implemented in a clinic setting in a Midwestern state. The purpose of clinic services was to provide support, assessment, and forensic examinations for adult women and to evaluate the number of women receiving services. A quality improvement approach was used to determine how and when sexually assault victims received sexual assault services. Persons who have been sexually assaulted vary in gender and age; however, for the purpose of the pilot project, implementation initially included services to women over 18 years of age. Although the number of female patients receiving care was low in the inaugural clinic during the implementation and evaluation period, the services provision remains a viable option for women who experienced sexual assault in a community that previously had no access to clinic services.
Digit Replantation under Wide-Awake Local Anesthesia
Authors: Huang Hui-Fu , Matschke Jan 
Published: November 2021

Background:
Digit replantation under wide-awake local anesthesia is a challenging method, and there are only a few works of literature on this procedure. This article describes the authors’ clinical experience in finger replantation under wide-awake local anesthesia compared to general anesthesia.

Methods:
Fifty-one patients who received single finger replantation after initial sharp amputation were included in the study, of whom 16 received wide-awake local anesthesia and 35 general anesthesia treatment. The indications for wide-awake local anesthesia were sharp amputation injury, estimated operation time less than 3 hours, and cooperative patients. The wide-awake local anesthesia was performed with 1% or 2% lidocaine infiltrated at the volar midpoint of the metacarpophalangeal joint of the affected digit without sedation medications. Demographic data included surgical outcome, waiting time, operation time, and hospital stay.

Results:
A total of 51 consecutive patients were included in this study. There were significantly shorter waiting times and operation times in the wide-awake local anesthesia group. The other parameters showed no significant differences. The overall success rate was 76.47 percent, with a mean overall operation time of 207 minutes.

Conclusions:
In selected patients, finger replantation can be successfully performed under wide-awake local anesthesia, which has lower anesthesia risk and fewer medical expenses than general anesthesia. The method is feasible for single-digit replantation. Therefore, the finger replantation under wide-awake local anesthesia is a practicable alternative to general anesthesia.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Development and validation of DNA Methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes
Authors: Cheng Yipeng , Gadd Danni A , Gieger Christian , Monterrubio-Gómez Karla , Zhang Yufei , Berta Imrich , Stam Michael J , Szlachetka Natalia , Lobzaev Evgenii , Wrobel Nicola , Murphy Lee , Campbell Archie , Nangle Cliff , Walker Rosie M , Fawns-Ritchie Chloe , Peters Annette , Rathmann Wolfgang , Porteous David J , Evans Kathryn L , McIntosh Andrew M , Cannings Timothy I , Waldenberger Melanie , Ganna Andrea , McCartney Daniel L , Vallejos Catalina A , Marioni Riccardo E 
Published: November 2021

AbstractType 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction and intervention. While standard risk factors have shown good predictive performance, we show that the use of blood-based DNA methylation information leads to a significant improvement in the prediction of 10-year T2D incidence risk.Previous studies have been largely constrained by linear assumptions, the use of CpGs one-at-a-time, and binary outcomes. We present a flexible approach (via an R package, MethylPipeR) based on a range of linear and tree-ensemble models that incorporate time-to-event data for prediction. Using the Generation Scotland cohort (training set ncases=374, ncontrols=9,461; test set ncases=252, ncontrols=4,526) our best-performing model (Area Under the Curve (AUC)=0.872, Precision Recall AUC (PRAUC)=0.302) showed notable improvement in 10-year onset prediction beyond standard risk factors (AUC=0.839, PRAUC=0.227). Replication was observed in the German-based KORA study (n=1,451, ncases = 142, p=1.6×10-5).
Optimizing transcranial direct current stimulation (tDCS) electrode position, size, and distance doubles the on-target cortical electric field: Evidence from 3000 Human Connectome Project models
Authors: Caulfield Kevin A. , George Mark S. 
Published: November 2021

AbstractTranscranial direct current stimulation (tDCS) is a widely used noninvasive brain stimulation technique with mixed results and no FDA-approved therapeutic indication to date. So far, thousands of published tDCS studies have placed large scalp electrodes directly over the intended brain target and delivered the same stimulation intensity to each person. Inconsistent therapeutic results may be due to insufficient cortical activation in some individuals and the inability to determine an optimal dose. Here, we computed 3000 MRI-based electric field models in 200 Human Connectome Project (HCP) participants, finding that the largely unexamined variables of electrode position, size, and between-electrode distance significantly impact the delivered cortical electric field magnitude. At the same scalp stimulation intensity, smaller electrodes surrounding the neural target deliver more than double the on-target cortical electric field while stimulating only a fraction of the off-target brain regions. This new optimized tDCS method can ensure sufficient cortical activation in each person and could produce larger and more consistent behavioral effects in every prospective research and transdiagnostic clinical application of tDCS.
Uncovering Xenobiotics in the Dark Metabolome using Ion Mobility Spectrometry, Mass Defect Analysis and Machine Learning
Authors: Foster MaKayla , Rainey Markace , Watson Chandler , Dodds James N. , Fernández Facundo M. , Baker Erin S. 
Published: November 2021

AbstractThe identification of xenobiotics in nontargeted metabolomic analyses is a vital step in understanding human exposure. Xenobiotic metabolism, excretion, and co-existence with other endogenous molecules however greatly complicate nontargeted studies. While mass spectrometry (MS)-based platforms are commonly used in metabolomic measurements, deconvoluting endogenous metabolites and xenobiotics is often challenged by the lack of xenobiotic parent and metabolite standards as well as the numerous isomers possible for each small molecule m/z feature. Here, we evaluate the use of ion mobility spectrometry coupled with MS (IMS-MS) and mass defect filtering in a xenobiotic structural annotation workflow to reduce large metabolomic feature lists and uncover potential xenobiotic classes and species detected in the metabolomic studies. To evaluate the workflow, xenobiotics having known high toxicities including per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were examined. Initially, to address the lack of available IMS collision cross section (CCS) values for per- and polyfluoroalkyl substances (PFAS), 88 PFAS standards were evaluated with IMS-MS to both develop a targeted PFAS CCS library and for use in machine learning predictions. The CCS values for biomolecules and xenobiotics were then plotted versus m/z, clearly distinguishing the biomolecules and halogenated xenobiotics. The xenobiotic structural annotation workflow was then used to annotate potential PFAS features in NIST human serum. The workflow reduced the 2,423 detected LC-IMS-MS features to 80 possible PFAS with 17 confidently identified through targeted analyses and 48 additional features correlating with possible CompTox entries.
Nrf2 mediated ER-phagy protects against oxidative damage in intervertebral disc degeneration
Authors: Lin Zhen , Ni Libin , Teng Cheng , Zhang Zhao , Lu Xinlei , Xie Chenglong , Wu Long , Zhou Yifei , Tian Naifeng , Wu Yaosen , Sun Liaojun , Pan Zongyou , Wang Xiangyang , Lin Zhongke , Zhang Xiaolei 
Published: November 2021

AbstractIntervertebral disc degeneration (IDD) increases the risk of low back pain (LBP). Oxidative stress may induce cellular damage and contribute to various diseases including IDD. Endoplasmic reticulum autophagy (ER-phagy) is a specific type of autophagy, its role in oxidative stress induced damage as well as in IDD is unknown. This study explores the role of ER-phagy in oxidative damage in intervertebral disc nucleus pulposus cells (NPCs), as well as the Nrf2/FAM134B axis in ER-phagy regulation and IDD therapy. We found ER-phagy was decreased in NPCs during oxidative stress; while FAM134B may promote ER-phagy and alleviate oxidative stress induced ER-stress and apoptosis. In addition, the nuclear transcription factor Nrf2 may promote the expression of FAM134B as well as ER-phagy, and suppress ER-stress and apoptosis in NPCs. Furthermore, overexpression of FAM134B and Nrf2 could effectively attenuate the progression of IDD in rats in vivo. These results suggest Nrf2/FAM134B mediated ER-phagy may combat oxidative damage in cells; meanwhile, ER-phagy as well as Nrf2 could be potential therapeutic targets for IDD.Graphical abstract
Heat stress prevented the biomass and yield stimulation caused by elevated CO2 in two well-watered wheat cultivars
Authors: Chavan Sachin G. , Duursma Remko A. , Tausz Michael , Ghannoum Oula 
Published: November 2021

AbstractTo investigate the interactive effects of elevated CO2 and heat stress (HS), we grew two contrasting wheat cultivars, early-maturing Scout and high-tillering Yitpi, under non-limiting water and nutrients at ambient (aCO2, 450 ppm) or elevated (eCO2, 650 ppm) CO2 and 22°C in the glasshouse. Plants were exposed to two 3-day HS cycles at the vegetative (38.1°C) and/or flowering (33.5°C) stage.At aCO2, both wheat cultivars showed similar responses of photosynthesis and mesophyll conductance to temperature and produced similar grain yield. Relative to aCO2, eCO2 enhanced photosynthesis rate and reduced stomatal conductance and maximal carboxylation rate (Vcmax). During HS, high temperature stimulated photosynthesis at eCO2 in both cultivars, while eCO2 stimulated photosynthesis in Scout. Electron transport rate (Jmax) was unaffected by any treatment. eCO2 equally enhanced biomass and grain yield of both cultivars in control, but not HS, plants. HS reduced biomass and yield of Scout at eCO2. Yitpi, the cultivar with higher grain nitrogen, underwent a trade-off between grain yield and nitrogen. In conclusion, eCO2 improved photosynthesis of control and HS wheat, and improved biomass and grain yield of control plants only. Under well-watered conditions, HS was not detrimental to photosynthesis or growth but precluded a yield response to eCO2.Key messageHigh temperatures increased photosynthetic rates only at eCO2 and photosynthesis was upregulated after recovery from heat stress at eCO2 in Scout suggesting that eCO2 increased optimum temperature of photosynthesis.
Post-translational modification patterns on β-myosin heavy chain are altered in ischemic and non-ischemic human hearts
Authors: Landim-Vieira Maicon , Childers Matthew C. , Wacker Amanda L. , Garcia Michelle Rodriguez , He Huan , Singh Rakesh , Brundage Elizabeth A. , Johnston Jamie R. , Whitson Bryan A. , Chase P. Bryant , Janssen Paul M.L. , Regnier Michael , Biesiadecki Brandon J. , Pinto J. Renato , Parvatiyar Michelle S. 
Published: November 2021

AbstractPhosphorylation and acetylation of sarcomeric proteins are important for fine-tuning myocardial contractility. Here, we used bottom-up proteomics and label-free quantification to identify novel post-translational modifications (PTMs) on beta-myosin heavy chain (β-MHC) in normal and failing human heart tissues. We report six acetylated lysines and two phosphorylated residues: K34-Ac, K58-Ac, S210-P, K213-Ac, T215-P, K429-Ac, K951-Ac, and K1195-Ac. K951-Ac was significantly reduced in both ischemic and non-ischemic failing hearts compared to non-diseased hearts. Molecular dynamics simulations show that K951-Ac may impact stability of thick filament tail interactions and ultimately myosin head positioning. K58-Ac altered the solvent exposed SH3 domain surface – known for protein-protein interactions – but did not appreciably change motor domain conformation or dynamics under conditions studied. Together, K213-Ac/T215-P altered loop 1’s structure and dynamics – known to regulate ADP-release, ATPase activity, and sliding velocity. Our study suggests that β-MHC acetylation levels may be influenced more by the PTM location than the type of heart disease since less protected acetylation sites are reduced in both heart failure groups. Additionally, these PTMs have potential to modulate interactions between β-MHC and other regulatory sarcomeric proteins, ADP-release rate of myosin, flexibility of the S2 region, and cardiac myofilament contractility in normal and heart failure hearts.
Ploidy variation and its implications for reproduction and population dynamics in two sympatric Hawaiian coral species
Authors: Stephens Timothy G. , Strand Emma L. , Putnam Hollie M. , Bhattacharya Debashish 
Published: November 2021

AbstractStanding genetic variation is a major driver of fitness and resilience, and therefore of fundamental importance for threatened species such as stony corals. We analyzed RNA- seq data generated from 132Montipora capitataand 119Pocillopora acutacoral colonies collected from Kāneʻohe Bay, Oʻahu, Hawaiʻi. Our goals were to determine the extent of colony genetic variation and to study reproductive strategies in these two sympatric species. Surprisingly, we found that 63% of theP. acutacolonies were triploid, with putative independent origins of the different triploid clades. These corals have spread primarilyviaasexual reproduction and are descended from a small number of genotypes, whose diploid ancestor invaded the bay. In contrast, allM. capitatacolonies are diploid, outbreeding, with almost all colonies genetically distinct. Only two cases of asexual reproduction, likelyviafragmentation, were identified in this species. We report two distinct strategies in sympatric coral species that inhabit the largest sheltered body of water in the main Hawaiian Islands. These data highlight divergence in reproductive behavior and genome biology, both of which contribute to coral resilience and persistence.Significance StatementGiven the threat posed to coral reef ecosystems by human caused climate change, there is a growing focus on developing strategies for the protection and restoration of these critical marine habitats. These efforts are however limited by our understanding of the diversity of coral survival and reproductive strategies. Our analysis of data from two coral species inhabiting the same Hawaiian bay found that one is a strict sexual outbreeder, whereas the other reproduces predominantly asexually (i.e., clonally) and includes both diploids and triploids. These results broaden our understanding of coral biology, adaptability, and evolution, and underpin future research into the mechanisms of coral resilience that can inform restoration activities.
A corticothalamic circuit trades off speed for safety during decision-making under motivational conflict
Authors: Choi Eun A , Husić Medina , Millan E. Zayra , Jean Richard dit Bressel Philip , McNally Gavan P. 
Published: November 2021

SummaryDecisions to act while pursuing goals in the presence of danger must be made quickly but safely. Premature decisions risk injury or death whereas postponing decisions risk goal loss. Here we show how mice resolve these competing demands. Using microstructural behavioral analyses, we identified the spatiotemporal dynamics of approach-avoidance decisions under motivational conflict. Then we used cognitive modelling to show that these dynamics reflect the speeded decision-making mechanisms used by humans and non-human primates, with mice trading off decision speed for safety of choice when danger loomed. Using calcium imaging and functional circuit analyses, we show that this speed-safety trade off occurs because increases in paraventricular thalamus (PVT) activity increase decision caution, thereby increasing approach-avoid decision times in the presence of danger. Our findings demonstrate that a discrete brain circuit involving the PVT and its prefrontal cortical input dynamically adjusts decision caution during motivational conflict, trading off decision speed for decision safety when danger is close. They identify the corticothalamic pathway as central to cognitive control during decision-making under conflict.
Simple and efficient differentiation of human iPSCs into contractible skeletal muscles for muscular disease modeling
Authors: Rashid Muhammad Irfanur , Ito Takuji , Shimojo Daisuke , Arimoto Kanae , Onodera Kazunari , Okada Rina , Nagashima Takunori , Yamamoto Kazuki , Khatun Zohora , Okano Hideyuki , Sakurai Hidetoshi , Shimizu Kazunori , Doyu Manabu , Okada Yohei 
Published: November 2021

ABSTRACTPathophysiological analysis and drug discovery targeting human diseases require disease models that suitably recapitulate patients’ pathology. Disease-specific human induced pluripotent stem cells (hiPSCs) can potentially recapitulate disease pathology more accurately than existing disease models when differentiated into affected cell types. Thus, successful modeling of muscular diseases requires efficient differentiation of hiPSCs into skeletal muscles. hiPSCs transduced with doxycycline-inducible MYOD1 (MYOD1-hiPSCs) have been widely used; however, they require time- and labor-consuming clonal selection procedures, and clonal variations must be overcome. Moreover, their functionality to exhibit muscular contraction has never been reported. Here, we demonstrated that bulk MYOD1- hiPSCs established with puromycin selection, but not with G418 selection, showed high differentiation efficiency, generating more than 80% Myogenin (MyoG)+ and Myosin heavy chain (MHC)+ muscle cells within seven days. Interestingly, bulk MYOD1-hiPSCs exhibited average differentiation properties compared with those of clonally established MYOD1- hiPSCs, suggesting that the bulk method may minimize the effects of clonal variations. Finally, three-dimensional muscle tissues were fabricated from bulk MYOD1-hiPSCs, which exhibited contractile force upon electrical pulse stimulation, indicating their functionality. Together, the findings indicate that our bulk differentiation requires less time and labor than existing methods, efficiently generates contractible skeletal muscles, and facilitates the generation of muscular disease models.Graphical Abstract
Multimodal Gradient Mapping of Rodent Hippocampus
Authors: Gunnarsdóttir Brynja , Zerbi Valerio , Kelly Clare 
Published: November 2021

AbstractThe hippocampus plays a central role in supporting our coherent and enduring sense of self and our place in the world. Understanding its functional organisation is central to understanding this complex role. Previous studies suggest function varies along a long hippocampal axis, but there is disagreement about the presence of sharp discontinuities or gradual change along that axis. Other open questions relate to the underlying drivers of this variation and the conservation of organisational principles across species. Here, we delineate the primary organisational principles underlying patterns of hippocampal functional connectivity (FC) in the mouse using gradient analysis on resting state fMRI data. We further applied gradient analysis to mouse gene co-expression data to examine the relationship between variation in genomic anatomy and functional organisation. Two principal FC gradients along a hippocampal axis were revealed. The principal gradient exhibited a sharp discontinuity that divided the hippocampus into dorsal and ventral compartments. The second, more continuous, gradient followed the long axis of the ventral compartment. Dorsal regions were more strongly connected to areas involved in spatial navigation while ventral regions were more strongly connected to areas involved in emotion, recapitulating patterns seen in humans. In contrast, gene co-expression gradients showed a more segregated and discrete organisation. Our findings suggest that hippocampal functional organisation exhibits both sharp and gradual transitions and that hippocampal genomic anatomy exerts a subtle influence on this organisation.
Two decades of suspect evidence for adaptive molecular evolution – Negative selection confounding positive selection signals
Authors: Chen Qipian , Yang Hao , Feng Xiao , Chen Qingjian , Shi Suhua , Wu Chung-I , He Ziwen 
Published: November 2021

AbstractThere is a large literature in the last two decades affirming adaptive DNA sequences evolution between species. The main lines of evidence are from i) the McDonald-Kreitman (MK) test, which compares divergence and polymorphism data, and ii) the PAML test, which analyzes multi-species divergence data. Here, we apply these two tests concurrently on the genomic data ofDrosophilaandArabidopsis. To our surprise, the >100 genes identified by the two tests do not overlap beyond random expectation. Because the non-concordance could be due to low powers leading to high false-negatives, we merge every 20 - 30 genes into a “supergene”. At the supergene level, the power of detection is large but the calls still do not overlap. We rule out methodological reasons for the non-concordance. In particular, extensive simulations fail to find scenarios whereby positive selection can only be detected by either MK or PAML, but not both. Since molecular evolution is governed by positive and negative selection concurrently, a fundamental assumption for estimating one (say, positive selection) is that the other is constant. However, in a broad survey of primates, birds,DrosophilaandArabidopsis, we found that negative selection rarely stays constant for long in evolution. As a consequence, the variation in negative selection is often mis-construed as signals of positive selection. In conclusion, MK, PAML or any method that examines genomic sequence evolution has to explicitly address the variation in negative selection before estimating positive selection. In a companion study, we propose a possible path forward in two stages – first, by mapping out the changes in negative selection and then using this map to estimate positive selection. For now, the large literature on positive selection between species has to await the re-assessment.