bluuebunny/crossref_metadata_2025 huggingface dataset:
Precise measurement of gene expression changes in mouse brain areas denervated by injury
Authors: Schlaudraff Jessica , Paul Mandy H. , Deller Thomas , Del Turco Domenico
Published: December 2022

Quantitative PCR (qPCR) is a widely used method to study gene expression changes following brain injury. The accuracy of this method depends on the tissue harvested, the time course analyzed and, in particular on the choice of appropriate internal controls, i.e., reference genes (RGs). In the present study we have developed and validated an algorithm for the accurate normalization of qPCR data using laser microdissected tissue from the mouse dentate gyrus after entorhinal denervation at 0, 1, 3, 7, 14 and 28 days postlesion. The expression stabilities of ten candidate RGs were evaluated in the denervated granule cell layer (gcl) and outer molecular layer (oml) of the dentate gyrus. Advanced software algorithms demonstrated differences in stability for single RGs in the two layers at several time points postlesion. In comparison, a normalization index of several stable RGs covered the entire post-lesional time course and showed high stability. Using these RGs, we validated our findings and quantified glial fibrillary acidic protein (Gfap) mRNA and allograft inflammatory factor 1 (Aif1/Iba1) mRNA in the denervated oml. We compared the use of single RGs for normalization with the normalization index and found that single RGs yield variable results. In contrast, the normalization index gave stable results. In sum, our study shows that qPCR can yield precise, reliable, and reproducible datasets even under such complex conditions as brain injury or denervation, provided appropriate RGs for the model are used. The algorithm reported here can easily be adapted and transferred to any other brain injury model.
Deaza-modification of MR1 ligands modulates recognition by MR1-restricted T cells
Authors: Jin Haihong , Ladd Nicole A. , Peev Andrew M. , Swarbrick Gwendolyn M. , Cansler Meghan , Null Megan , Boughter Christopher T. , McMurtrey Curtis , Nilsen Aaron , Dobos Karen M. , Hildebrand William H. , Lewinsohn Deborah A. , Adams Erin J. , Lewinsohn David M. , Harriff Melanie J.
Published: December 2022

MR1-restricted T (MR1T) cells recognize microbial small molecule metabolites presented on the MHC Class I-like molecule MR1 and have been implicated in early effector responses to microbial infection. As a result, there is considerable interest in identifying chemical properties of metabolite ligands that permit recognition by MR1T cells, for consideration in therapeutic or vaccine applications. Here, we made chemical modifications to known MR1 ligands to evaluate the effect on MR1T cell activation. Specifically, we modified 6,7-dimethyl-8-d-ribityllumazine (DMRL) to generate 6,7-dimethyl-8-d-ribityldeazalumazine (DZ), and then further derivatized DZ to determine the requirements for retaining MR1 surface stabilization and agonistic properties. Interestingly, the IFN-γ response toward DZ varied widely across a panel of T cell receptor (TCR)-diverse MR1T cell clones; while one clone was agnostic toward the modification, most displayed either an enhancement or depletion of IFN-γ production when compared with its response to DMRL. To gain insight into a putative mechanism behind this phenomenon, we used in silico molecular docking techniques for DMRL and its derivatives and performed molecular dynamics simulations of the complexes. In assessing the dynamics of each ligand in the MR1 pocket, we found that DMRL and DZ exhibit differential dynamics of both the ribityl moiety and the aromatic backbone, which may contribute to ligand recognition. Together, our results support an emerging hypothesis for flexibility in MR1:ligand-MR1T TCR interactions and enable further exploration of the relationship between MR1:ligand structures and MR1T cell recognition for downstream applications targeting MR1T cells.
A genome-wide association study of tinnitus reveals shared genetic links to neuropsychiatric disorders
Authors: Bhatt Ishan Sunilkumar , Wilson Nicholas , Dias Raquel , Torkamani Ali
Published: December 2022

Tinnitus, a phantom perception of sound in the absence of any external sound source, is a prevalent health condition often accompanied by psychiatric comorbidities. Recent genome-wide association studies (GWAS) highlighted a polygenic nature of tinnitus susceptibility. A shared genetic component between tinnitus and psychiatric conditions remains elusive. Here we present a GWAS using the UK Biobank to investigate the genetic processes linked to tinnitus and tinnitus-related distress, followed by gene-set enrichment analyses. The UK Biobank sample comprised 132,438 individuals with tinnitus and genotype data. Among the study sample, 38,525 individuals reported tinnitus, and 26,889 participants mentioned they experienced tinnitus-related distress in daily living. The genome-wide association analyses were conducted on tinnitus and tinnitus-related distress. We conducted enrichment analyses using FUMA to further understand the genetic processes linked to tinnitus and tinnitus-related distress. A genome-wide significant locus (lead SNP: rs71595470) for tinnitus was obtained in the vicinity of GPM6A. Nineteen independent loci reached suggestive association with tinnitus. Fifteen independent loci reached suggestive association with tinnitus-related distress. The enrichment analysis revealed a shared genetic component between tinnitus and psychiatric traits, such as bipolar disorder, feeling worried, cognitive ability, fast beta electroencephalogram, and sensation seeking. Metabolic, cardiovascular, hematological, and pharmacological gene sets revealed a significant association with tinnitus. Anxiety and stress-related gene sets revealed a significant association with tinnitus-related distress. The GWAS signals for tinnitus were enriched in the hippocampus and cortex, and for tinnitus-related distress were enriched in the brain and spinal cord. This study provides novel insights into genetic processes associated with tinnitus and tinnitus-related distress and demonstrates a shared genetic component underlying tinnitus and psychiatric conditions. Further collaborative attempts are necessary to identify genetic components underlying the phenotypic heterogeneity in tinnitus and provide biological insight into the etiology.
Pictograms to aid laypeople in identifying the addictiveness of gambling products (PictoGRRed study)
Authors: Luquiens Amandine , Guillou Morgane , Giustiniani Julie , Barrault Servane , Caillon Julie , Delmas Helena , Achab Sophia , Bento Bruno , Billieux Joël , Brevers Damien , Brody Aymeric , Brunault Paul , Challet-Bouju Gaëlle , Chóliz Mariano , Clark Luke , Cornil Aurélien , Costes Jean-Michel , Devos Gaetan , Díaz Rosa , Estevez Ana , Grassi Giacomo , Hakansson Anders , Khazaal Yasser , King Daniel L. , Labrador Francisco , Lopez-Gonzalez Hibai , Newall Philip , Perales José C. , Ribadier Aurélien , Sescousse Guillaume , Sharman Stephen , Taquet Pierre , Varescon Isabelle , Von Hammerstein Cora , Bonjour Thierry , Romo Lucia , Grall-Bronnec Marie
Published: December 2022

The structural addictive characteristics of gambling products are important targets for prevention, but can be unintuitive to laypeople. In the PictoGRRed (Pictograms for Gambling Risk Reduction) study, we aimed to develop pictograms that illustrate the main addictive characteristics of gambling products and to assess their impact on identifying the addictiveness of gambling products by laypeople. We conducted a three-step study: (1) use of a Delphi consensus method among 56 experts from 13 countries to reach a consensus on the 10 structural addictive characteristics of gambling products to be illustrated by pictograms and their associated definitions, (2) development of 10 pictograms and their definitions, and (3) study in the general population to assess the impact of exposure to the pictograms and their definitions (n = 900). French-speaking experts from the panel assessed the addictiveness of gambling products (n = 25), in which the mean of expert’s ratings was considered as the true value. Participants were randomly provided with the pictograms and their definitions, or with a standard slogan, or with neither (control group). We considered the control group as representing the baseline ability of laypeople to assess the addictiveness of gambling products. Each group and the French-speaking experts rated the addictiveness of 14 gambling products. The judgment criterion was the intraclass coefficients (ICCs) between the mean ratings of each group and the experts, reflecting the level of agreement between each group and the experts. Exposure to the pictograms and their definition doubled the ability of laypeople to assess the addictiveness of gambling products compared with that of the group that read a slogan or the control group (ICC = 0.28 vs. 0.14 (Slogan) and 0.14 (Control)). Laypeople have limited awareness of the addictive characteristics of gambling products. The pictograms developed herein represent an innovative tool for universally empowering prevention and for selective prevention.
The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction
Authors: Kim Jeong-Min , Lee Reeree , Jeong Hae-Bong , Park Kwang-Yeol , Seok Ju Won
Published: December 2022

Positron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60–4.2] versus 0.20 [0.10–0.40], p = 0.021 by Mann–Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke.
Global urban homogenization and the loss of emotions
Authors: Grêt-Regamey Adrienne , Galleguillos-Torres Marcelo
Published: December 2022

Urban expansion is generating unprecedented homogenization of landscapes across the world. This uniformization of urban forms brings along dramatic environmental, social, and health problems. Reverting such processes requires activating people’s sense of place, their feeling of caring for their surroundings, and their community engagement. While emotions are known to have a modulating effect on behavior, their role in urban transformation is unknown. Drawing on large cognitive-psychological experiments in two countries, we demonstrate for the first time that urban homogenization processes lower people’s affective bounds to places and ultimately their intentions to engage with their neighbourhoods. The dulled emotional responses in peri-urban areas compared to urban and rural areas can be explained by lower social cohesion and place attachment. The findings highlight the significance of considering emotions in shaping just, equitable, sustainable, and resilient cities.
Binding affinity estimation from restrained umbrella sampling simulations
Authors: Govind Kumar Vivek , Polasa Adithya , Agrawal Shilpi , Kumar Thallapuranam Krishnaswamy Suresh , Moradi Mahmoud
Published: December 2022

The protein–ligand binding affinity quantifies the binding strength between a protein and its ligand. Computer modeling and simulations can be used to estimate the binding affinity or binding free energy using data- or physics-driven methods or a combination thereof. Here we discuss a purely physics-based sampling approach based on biased molecular dynamics simulations. Our proposed method generalizes and simplifies previously suggested stratification strategies that use umbrella sampling or other enhanced sampling simulations with additional collective-variable-based restraints. The approach presented here uses a flexible scheme that can be easily tailored for any system of interest. We estimate the binding affinity of human fibroblast growth factor 1 to heparin hexasaccharide based on the available crystal structure of the complex as the initial model and four different variations of the proposed method to compare against the experimentally determined binding affinity obtained from isothermal titration calorimetry experiments.
Acyl azide modification of the ubiquitin C-terminus enables DUB capture
Authors: Hua Xiao , Guo Yanyan , Wang Yu , Chu Guo-Chao , Li Pincheng , Shi Jing
Published: December 2022

A Ub C-terminal acyl azide was synthesized and found to be able to capture DUBs.
Solvent dependent iodide oxidation in metal-halide perovskite precursor solutions
Authors: Radicchi Eros , Quaglia Giulia , Latterini Loredana , De Angelis Filippo
Published: December 2022

Triiodide (I3−) is a species well-known to influence the nature of perovskite materials. Here, we highlight possible and unexpected sources of I3−, i.e. the iodide (I−) salt solutions used for the synthesis of metal-halide perovskites.
Plant-based dietary patterns and their association with mood in healthy individuals
Authors: Ma Xuemei , Li Yong , Xu Yifan , Gibson Rachel , Williams Claire , Lawrence Andrew J. , Nosarti Chiara , Dazzan Paola , Rodriguez-Mateos Ana
Published: December 2022

Original Mediterranean Diet and Altered Mediterranean Diet were associated with positive mood when adjusted for sex and age in healthy people. Plant-based Diet Index was only associated with children’s positive mood.
Nitrogen-doped carbon sponge derived from the self-assembly of poly(amic acid) for high performance oxygen reduction reaction
Authors: Sun Hui , Jin Kai , Li Xiao , Wang Tian , Lai Xiaoyong
Published: December 2022

Nitrogen-doped carbon sponge with high porosity and ultrathin frameworks derived from the self-assembly of poly(amic acid) for high performance ORR.
Overall structure of Au12Ag60(S-c-C6H11)31Br9(Dppp)6: achieving a stronger assembly of icosahedral M13units
Authors: Zhou Manman , Li Kang , Wang Pu , Zhou Huimin , Jin Shan , Pei Yong , Zhu Manzhou
Published: December 2022

[Au12Ag60(S-c-C6H11)31Br9(Dppp)6]Br2has provided a breakthrough in icosahedral assemblies,i.e., achieving a twelve-mer assembly, helping to elucidate the fusion growth of M13-based assembled nanoclusters and their geometric/electronic structure correlations.
Mechanistic insights into the challenges of organocatalytic Beckmann rearrangement reactions
Authors: Tataroğlu Melin , Sungur Fethiye Aylin
Published: December 2022

The Beckmann rearrangement via a Meisenheimer complex is an alternative to the self-propagating pathway under specific experimental conditions.
Two novel Pd thiosemicarbazone complexes as efficient and selective antitumoral drugs
Authors: Hidalgo Tania , Fabra David , Allende Raul , Matesanz Ana I. , Horcajada Patricia , Biver Tarita , Quiroga Adoracion G.
Published: December 2022

Two Palladium complexes are presented as a promising alternative to platinum drugs disadvantages, controlling the speciation and limiting toxicity. Their interaction vs. biological targets and their efficiency are demonstrated, being more specific than the benchmark cisplatin drug.
Recent advances in metal–organic framework based heterogeneous catalysts for furfural hydrogenation reactions
Authors: Fu Qiuju , Jiang Huimin , Wang Yujia , Wang Haiyan , Zhao Xuebo
Published: December 2022

This review summarizes the recent advances in upgrading FFR to high value-added chemicals using MOF-based heterogeneous catalysts.
Recent advances in Ru-based electrocatalysts for oxygen evolution reaction
Authors: Ying Jie , Chen Jiang-Bo , Xiao Yu-Xuan , Cordoba de Torresi Susana I. , Ozoemena Kenneth I. , Yang Xiao-Yu
Published: December 2022

Recently reported ruthenium (Ru)-based catalysts for the oxygen evolution reaction (OER) falling in the Ru metal and Ru compound subclasses are summarized with special emphasis being given to a discussion of activity/stability-enhancing strategies.
Charge modulation over atomically precise metal nanoclusters via non-conjugated polymers for photoelectrochemical water oxidation
Authors: Xiao Yang , Mo Qiao-Ling , Wu Gao , Wang Kun , Ge Xing-Zu , Xu Shu-Ran , Li Jia-Le , Wu Yue , Xiao Fang-Xing
Published: December 2022

Electron tunneling was stimulated over atomically precise metal nanoclusters via insulating polymers for engendering tandem charge transfer towards boosted solar water oxidation.
Clothing CsPbI3 perovskite in a robust phase-pure armor to boost the thermal stability
Authors: Tan Xue , Wang Shubin , Zhang Qixian , Wang Hailiang , Liu Huicong , Li Weiping , Zhu Liqun , Song Tinglu , Cui Zhenhua , Bai Yang , Chen Haining
Published: December 2022

The intermediate treatment (IT) strategy was developed to clothe the CsPbI3 perovskite in a robust phase-pure armor to boost its thermal stability.
A low-power and flexible bioinspired artificial sensory neuron capable of tactile perceptual and associative learning
Authors: Xia Qing , Qin Yuxiang , Zheng Anbo , Qiu Peilun
Published: December 2022

A flexible and low energy consumption artificial tactile neuron was proposed and experimentally demonstrated by integrating a dual network hydrogel-based sensor and a low power memristor.
Fabrication of Pt cluster-loaded In2O3 inverse opal photonic crystals for fast and highly sensitive ethanol sensing
Authors: Li Feihu , Jing Junjie , Li Jinkun , Li Shuni , Cheng Dongliang , Zhang Yeguang , Zhan Zili , Tang Bingtao
Published: December 2022

Pt cluster-loaded In2O3 inverse opal photonic crystals were fabricated, and displayed a significantly improved response to ethanol (Ra/Rg = 103 to 50 ppm) and an ultra-fast response/recovery time (7/9 s).
Speech Error Variability and Phonological Awareness in Preschoolers
Authors: Roepke Elizabeth , Brosseau-Lapré Françoise
Published: December 2022

Purpose:

The purpose of this article was to investigate the relationship between speech error variability and phonological awareness.

Method:

This article begins with a narrative review of the theoretical interpretation of speech error variability. The post hoc exploratory analysis of the relationship between speech error variability and phonological awareness included 40 children: 20 with typical speech and language and 20 with speech sound disorder and typical language. Groups were matched on gender, age, maternal education, receptive and expressive vocabulary, nonverbal intelligence, and expressive morphosyntax. Multiple regression was used to identify the best fit model for the relationship between vocabulary, speech errors, and phonological awareness.

Results:

Segmental variability was associated with poor phonological awareness in preschool-aged children.

Conclusion:

Children with high levels of segmental variability have poor phonological awareness, likely due to unstable phonological representations.
Effects of Target and Masker Fundamental Frequency Contour Depth on School-Age Children's Speech Recognition in a Two-Talker Masker
Authors: Flaherty Mary M. , Buss Emily , Libert Kelsey
Published: December 2022

Purpose:

Maturation of the ability to recognize target speech in the presence of a two-talker speech masker extends into early adolescence. This study evaluated whether children benefit from differences in fundamental frequency (
f
o
) contour depth between the target and masker speech, a cue that has been shown to improve recognition in adults.

Method:

Speech stimuli were recorded from talkers using three speaking styles, with
f
o
contour depths that were Flat, Normal, or Exaggerated. Targets were open-set, declarative sentences produced by a female talker, and maskers were two streams of concatenated sentences produced by a second female talker. Listeners were children (ages 5–17 years) and adults (ages 18–24 years) with normal hearing. Each listener was tested in one of the three masker styles paired with all three target styles. Speech recognition thresholds (SRTs) corresponding to 50% correct were estimated by fitting psychometric functions to adaptive track data.

Results:

For adults, performance did not differ significantly across conditions with matched speaking styles. A mismatch benefit was observed when combining Flat targets with the Exaggerated masker and Exaggerated targets with the Flat masker, and for both Flat and Exaggerated targets paired with the Normal masker. For children, there was a significant effect of age in all conditions. Flat targets in the Flat masker were associated with lower SRTs than the other two matched conditions, and a mismatch benefit was observed for young children only when the target
f
o
contour was less variable than the masker
f
o
contour.

Conclusions:

Whereas child-directed speech often has exaggerated pitch contours, young children were better able to recognize speech with less variable
f
o
. Age effects were observed in the benefit of mismatched speaking styles for some conditions, which could be related to differences in baseline SRTs rather than differences in segregation abilities.
Fatigue-Related Change in Surface Electromyographic Activities of the Perilaryngeal Muscles
Authors: Yiu Edwin M.-L. , Lau Gary W. H. , Wang Feifan
Published: December 2022

Purpose:

This study set out to quantify the fatigue-related changes in surface electromyographic (sEMG) activities of the perilaryngeal muscles following a vocal loading task.

Method:

Thirty-six young healthy participants (
M
age
= 22.4 years) with normal voice performed karaoke singing for at least 100 min. Before the singing task, all participants underwent the sEMG measure and completed a Perceived Vocal Fatigue Score (P-VFS) questionnaire. After the singing task, all participants were immediately measured with the P-VFS again. Half of the participants were then measured for their sEMG immediately after their karaoke singing task, and the other half were given 20 min of rest before undertaking the sEMG measure. The P-VFS and the median frequency (MDF) of the sEMG signals collected from the suprahyoid, infrahyoid, and sternocleidomastoid muscles before and after the singing task were compared using a linear mixed-effects model.

Results:

All participants reported a perceived vocal fatigue after singing, with a significantly increased P-VFS. Compared with the presinging baseline, the MDF of the sEMG signals in perilaryngeal muscles was significantly lower immediately after the singing task. Such a significant difference was also found after 20 min following the singing task.

Conclusions:

The MDF analysis of the sEMG signals could identify and quantify the performance vocal fatigue contributed by perilaryngeal muscles following a vocal loading task. The findings also showed that such fatigue in perilaryngeal muscles, as far as sEMG activities are concerned, can last for at least 20 min.
Multi‐feature fusion attention network for single image super‐resolution
Authors: Chen Jiacheng , Wang Wanliang , Xing Fangsen , Tu Hangyao
Published: December 2022

Single Image Super‐Resolution algorithms have made enormous progress in recent years. However, many previous Convolution Neural Network (CNN) based Super‐Resolution algorithms only stack uniform convolution layers of fixed kernel size, and frequently ignore inherent multi‐scale properties of the images, resulting in unsatisfactory reconstruction results. Here, a multi‐feature fusion attention network (MFFAN) is proposed for capturing information at diverse scales. MFFAN is composed of multiple efficient sparse residual group (ESRG) modules. Several multi‐scale feature fusion blocks (MSFFB) are constructed using a cascade manner in each ESRG module and it is capable of exploiting various cross scales information. Subsequently, a local‐global spatial attention block (LGSAB) is inserted at the tail of the ESRG module for further improving the interaction of inter‐pixel, which strengths essential features and suppresses irrelevant information. Additionally, owing to the fact that only feeding final output into the reconstruction layer has exacerbated the long‐range dependency problems, an enhanced hierarchy feature fusion block (EHFFB) is designed to fuse low‐level information and high‐level semantic information. Experiment results indicate that the proposed MFFAN is competitive in comparison to several state‐of‐the‐art algorithms.
Infantile Spasms without Hypsarrhythmia and Paroxysmal Eye–Head Movements in an Infant with a Pyridoxine-Dependent Epilepsy due to PLPBP/PLPHP Deficiency
Authors: Kalser Judith , Giuliano Fabienne , Peralta Maria , Plecko Barbara , Bölsterli Bigna K.
Published: December 2022

To describe a new phenotype and the diagnostic workup of a vitamin-B6-dependent epilepsy due to pyridoxal 5′-phosphate-binding protein (PLPBP) deficiency in an infant with early-onset epilepsy at the age of 5 years 6 months. Following immediate and impressive clinical response to treatment with pyridoxine, metabolic screening for vitamin-B6-dependent epilepsies and targeted next-generation sequencing (NGS)-based gene panel analysis were performed. Potentially pathogenic variants were confirmed by Sanger sequencing in the patient, and variants were analyzed in both parents to confirm biallelic inheritance. The clinical phenotype and course of disease were compared to the 44 cases reported in the literature, harboring variants in pyridoxal phosphate homeostasis protein (PLPHP) and with cases of vitamin-B6-dependent epilepsy due to other known causative genes. Levels of alpha-aminoadipic semialdehyde in urine and amino acids were normal. Two inherited pathogenic variations in PLPHP were found in compound heterozygosity, including one novel deletion. We here describe a previously unreported individual harboring biallelic pathogenic PLPHP variants presenting with paroxysmal eye–head movements followed by epileptic spasms and an almost normal interictal electroencephalogram, thus expanding the clinical spectrum of PLPBP deficiency. This warrants consideration of vitamin-B6-dependent epilepsies in patients with early-onset epilepsy, including epileptic spasms, and eye movement disorders also beyond the neonatal period even when metabolic screening for vitamin-B6-dependent epilepsies is negative. PLPHP should be included systematically in NGS epilepsy gene panels.
Forty-Eight Hour Ex Vivo Perfusion and Two-Hour Simulated Reperfusion after a Major Traumatic Upper Extremity Amputation
Authors: Stögner Viola Antonia , Neubert Lavinia , Kaltenborn Alexander , Wiegmann Bettina , Krettek Christian , Vogt Peter Maria , Krezdorn Nicco
Published: December 2022

Background Extremity replantation as well as allotransplantation aim to restore form and function of the amputated limb. Both approaches, however, are clearly limited by the ischemic time. Ex vivo perfusion (EVP), already well-established in the field of solid organ transplantation, represents a promising tool to overcome this restriction.

Methods We have currently established the technical requirements to provide EVP to severed limbs in a clinical hospital setting and hereby report of a 48-hour hypothermic EVP (EVP48) of an upper extremity amputated at the level of the proximal humerus, followed by a 2-hour simulated reperfusion (2SR) with donor blood.

Results Muscle biopsies revealed histopathologically well preserved, vital muscle tissue after EVP24, and partially grouped muscle fiber necrosis with predominantly vital muscle tissue after EVP48 and 2SR. Analyses of perfusate samples showed a marked decline of biochemical muscle damage markers during EVP48. Cytokine analysis disclosed an isolated increase of the proinflammatory cytokines, interleukine-6, monocyte chemotactic protein-1, and interferon-γ, during EVP and 2SR. Magnetic resonance imaging, performed after EVP48, indicated partial muscle necrosis of the intrinsic hand muscles only, while no signs for infection or inflammation were present.

Conclusion Our single case experience shows the general feasibility of an amputated limb ex vivo salvage perfusion setting to allow for delayed replantation up to 24 hours. Nevertheless, an accurate prior planning is crucial to ensure successful implementation of EVP in the acute clinical setting.
Evaluation of an Online Decision Aid for Selection of Contraceptive Methods
Authors: Redman Molly , Brian Jennifer , Wang Dongwen
Published: December 2022

Objectives Knowledge gaps in contraceptives led to their low adoption rates and misuse in young women. The existing online contraception decision aids missed certain decision factors deemed important to college-aged women and did not consistently provide clear and accurate recommendations. To address the needs of young women and the limitations in current tools, we developed a prototype contraception decision aid, My Contraceptive Choice (MCC). This article reports an evaluation study of the MCC tool.

Methods We conducted a mixed methods study: (1) to assess MCC's usefulness and usability through an online survey and a follow-up focus group, and (2) to provide a quantitative examination on the recommendations generated by MCC to match with individual user's needs and preferences through simulated test cases.

Results The survey of 150 college-aged women showed very positive responses (reflecting personal preferences, 75%; helping people learn more about birth control methods, 88%; easy to navigate, 91%). The follow-up focus group of 10 survey participants reconfirmed most findings from the survey and provided detailed feedback on certain system functions, such as the inclusion of an important decision factor of weight gain and the efficient hybrid design to integrate the customized recommendations with the side-by-side comparison of all contraceptive methods. Simulated test cases showed that the MCC tool achieved an accuracy of 72% in addressing user preferences and an accuracy of 72% in satisfying user needs, which were significantly better than the existing Planned Parenthood tool.

Conclusion The initial evaluations suggest that the MCC tool has achieved good levels of usefulness, usability, and appropriate recommendations to address user needs and preferences. Future research is required to assess the performance of the MCC tool in naturalistic settings and to examine the generalizability of the findings to other user populations.
Oncological Outcomes of Nipple-Sparing Mastectomy in an Unselected Population Evaluated in a Single Center
Authors: Cavalcante Francisco Pimentel , Araújo Mirella Macedo Parente , Veras Igor Moreira , Freitas-Junior Ruffo
Published: December 2022

Objective Nipple-sparing mastectomy (NSM) has been traditionally used in selected cases with tumor-to-nipple distance > 2 cm and negative frozen section of the base of the nipple. Recommending NSM in unselected populations remains controversial. The present study evaluated the oncological outcomes of patients submitted to NSM in an unselected population seen at a single center.

Methods This retrospective cohort study included unselected patients with invasive carcinoma or ductal carcinoma in situ (DCIS) who underwent NSM in 2010 to 2020. The endpoints were locoregional recurrence, disease-free survival (DFS), and overall survival (OS), irrespective of tumor size or tumor-to-nipple distance.

Results Seventy-six patients (mean age 46.1 years) (58 invasive carcinomas/18 DCIS) were included. The most invasive carcinomas were hormone-positive (60%) (HER2 overexpression: 24%; triple-negative: 16%), while 39% of DCIS were high-grade. Invasive carcinomas were T2 in 66% of cases, with axillary metastases in 38%. Surgical margins were all negative. All patients with invasive carcinoma received systemic treatment and 38% underwent radiotherapy. After a mean of 34.8 months, 3 patients with invasive carcinoma (5.1%) and 1 with DCIS (5.5%) had local recurrence. Two patients had distant metastasis and died during follow-up. The 5-year OS and DFS rates for invasive carcinoma were 98% and 83%, respectively.

Conclusion In unselected cases, the 5-year oncological outcomes following NSM were found to be acceptable and comparable to previous reports. Further studies are required.
Ischemic stroke with unknown onset of symptoms: current scenario and perspectives for the future
Authors: Lopes Rônney Pinto , Gagliardi Vivian Dias Baptista , Pacheco Felipe Torres , Gagliardi Rubens José
Published: December 2022

Background Stroke is a major cause of disability worldwide and a neurological emergency. Intravenous thrombolysis and mechanical thrombectomy are effective in the reperfusion of the parenchyma in distress, but the impossibility to determine the exact time of onset was an important cause of exclusion from treatment until a few years ago.

Objectives To review the clinical and radiological profile of patients with unknown-onset stroke, the imaging methods to guide the reperfusion treatment, and suggest a protocol for the therapeutic approach.

Methods The different imaging methods were grouped according to current evidence-based treatments.

Results Most studies found no difference between the clinical and imaging characteristics of patients with wake-up stroke and known-onset stroke, suggesting that the ictus, in the first group, occurs just prior to awakening. Regarding the treatment of patients with unknown-onset stroke, four main phase-three trials stand out: WAKE-UP and EXTEND for intravenous thrombolysis, and DAWN and DEFUSE-3 for mechanical thrombectomy. The length of the therapeutic window is based on the diffusion weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) mismatch, core-penumbra mismatch, and clinical core mismatch paradigms. The challenges to approach unknown-onset stroke involve extending the length of the time window, the reproducibility of real-world imaging modalities, and the discovery of new methods and therapies for this condition.

Conclusion The advance in the possibilities for the treatment of ischemic stroke, while guided by imaging concepts, has become evident. New studies in this field are essential and needed to structure the health care services for this new scenario.
Current Postlaunch Implementation of State Mandates of Newborn Screening for Critical Congenital Heart Disease by Pulse Oximetry in U.S. States and Hospitals
Authors: Sakai-Bizmark Rie , Chang Ruey-Kang R. , Martin Gerard R. , Hom Lisa A. , Marr Emily H. , Ko Jamie , Goff Donna A. , Mena Laurie A. , von Kohler Connie , Bedel Lauren E. M. , Murillo Mary , Estevez Dennys , Hays Ron D.
Published: December 2022

Objective Our objective was to gauge adherence to nationally endorsed protocols in implementation of pulse oximetry (POx) screening for critical congenital heart disease (CCHD) in infants after mandate by all states and to assess associated characteristics.

Study Design Between March and October 2019, an online questionnaire was administered to nurse supervisors who oversee personnel conducting POx screening. The questionnaire used eight questions regarding performance and interpretation of screening protocols to measure policy consistency, which is adherence to nationally endorsed protocols for POx screening developed by professional medical societies. Multilevel linear regression models evaluated associations between policy consistency and characteristics of hospitals and individuals, state of hospital location, early versus late mandate adopters, and state reporting requirements.

Results Responses from 189 nurse supervisors spanning 38 states were analyzed. Only 17% received maximum points indicating full policy consistency, and 24% selected all four options for potential hypoxia that require a repeat screen. Notably, 33% did not recognize ≤90% SpO2 as an immediate failed screen and 31% responded that an infant with SpO2 of 89% in one extremity will be rescreened by nurses in an hour rather than receiving an immediate physician referral. Lower policy consistency was associated with lack of state reporting mandates (beta = –1.23 p = 0.01) and early adoption by states (beta = –1.01, p < 0.01).

Conclusion When presented with SpO2 screening values on a questionnaire, a low percentage of nurse supervisors selected responses that demonstrated adherence to nationally endorsed protocols for CCHD screening. Most notably, almost one-third of respondents did not recognize ≤90% SpO2 as a failed screen that requires immediate physician follow-up. In addition, states without reporting mandates and early adopter states were associated with low policy consistency. Implementing state reporting requirements might increase policy consistency, but some inconsistency may be the result of unique protocols in early adopter states that differ from nationally endorsed protocols.

Key Points
Urinary Tract Infections in Low Birth Weight Neonates
Authors: Janardhan Shruthi , Kim Sharon , Cukovic Blerim , Demissie Seleshi , Roth Philip , Blau Jonathan
Published: December 2022

Objective Our objective was to evaluate the incidence of urinary tract infections (UTIs) in low birth weight (LBW) neonates and to evaluate the compliance of neonatal intensive care unit (NICU) providers in performing urine cultures as a part of late-onset sepsis (LOS) evaluations following an educational intervention.

Study Design A retrospective chart review for all LBW infants undergoing LOS evaluations was performed. An educational intervention was conducted to encourage NICU providers to perform urine cultures in LOS evaluations. Prospective chart reviews were conducted following the intervention to assess compliance with the urine culture directive and the incidence of UTIs before and after the intervention.

Results Rate of UTIs among LBW neonates was 1.3% for the entire study period and typical uropathogens were the cause. UTIs were found concurrently with bacteremia in only 33.3% of cases and showed a predilection for male infants when analyzing based on the number of infections. Urine cultures were performed in 20% of LOS evaluations prior to our educational intervention and increased to 57% (p < 0.0001) postintervention.

Conclusion An educational intervention is effective at increasing the rate of obtaining urine cultures with LOS evaluations. Performing these cultures reveals that UTIs in LBW neonates are common without bacteremia and can be missed if they are omitted from LOS evaluations.

Key Points
A Comprehensive Review on Phytochemistry and Pharmacology of Homoeopathic Medicine Rhus Toxicodendron
Authors: Goswami Abanti , Saka Vara Prasad , GV Narasimha Kumar , Biswas Bibaswan
Published: December 2022

Background Rhus toxicodendron is a homoeopathic medicine introduced into the homoeopathic system by Hahnemann in 1816, and ever since, it has been used to relieve arthritis, rheumatism and skin disorders.

Aim This review aimed to search the literature for the phytochemical and pharmacological investigations of homeopathic medicine Rhus tox. The assembled data of Rhus tox could be beneficial in helping researchers concentrate on the most pivotal aspects that still need to be examined.

Discussion In the Homoeopathic Pharmacopoeia of India, Toxicodendron pubescens P. Mill (Atlantic poison oak) and Toxicodendron radicans (poison ivy) have been mentioned as synonyms of Rhus toxicodendron Linn. The allergic contact dermatitis caused by touching the leaves of the Toxicodendron plants is believed to give the plant its specific name. Available literature illustrated the medicinal and pharmacological potential against various inflammatory diseases, including arthritis, showing immunomodulatory and anti-neoplastic activity.

Conclusion There is a need to establish evidence for the activities mentioned in the literature. The detailed knowledge regarding the mechanism of Rhus toxicodendron Linn. would help the scientific community understand the field of homeopathic medicine more closely.
Chronic inflammatory demyelinating polyneurophaty: assessment of the cognitive function and quality of life
Authors: Kozow Larissa , Pupe Camila , Nascimento Osvaldo J. M.
Published: December 2022

Background Studies were carried out with the objective of evaluating the quality of life (QoL) of patients affected by chronic inflammatory demyelinating polyradiculopathy (CIDP). However, the cognitive issue is still little addressed.

Objectives To assess the QoL and cognitive impairment of patients with CIDP and to analyze whether there is a correlation between these parameters.

Methods Seven patients with CIDP and seven paired controls were subjected to: mini-mental state examination (MMSE); Montreal cognitive assessment (MoCA); digit symbol replacement/symbol copy test (DSST); fatigue severity scale (FSS); Beck depressive inventory-I (BDI-I), and a short-form of health survey (SF-36).

Results The mean age of the participants was 50 years (71.4% male). The MMSE and MoCA had no statistical difference between the groups. Patients showed superior results in the memory domain in the MoCA (5 vs. 2, p = 0.013). In the DSST, we observed a tendency for patients to be slower. There was a strong negative correlation between fatigue levels and vitality domain (SF-36). There was no significant correlation between depression levels and QoL, and there was no correlation between depression and the results obtained in the cognitive tests. The patients presented higher levels of depression (15.28 vs. 3.42, p < 0.001). A total of 57% had severe fatigue, 28.8% self-reported pain, and 57.1% complained of cramps.

Conclusion There was no cognitive impairment in these patients. However, there was a tendency of slower processing speed. To better evaluate the alterations found, a study with a larger number of individuals would be necessary. Chronic inflammatory demyelinating polyradiculopathy affects the QoL of patients in different ways.
Risk of perioperative stroke and cerebral autoregulation monitoring: a systematic review
Authors: Santos Daniel Paes de Almeida dos , Thirumala Parthasarathy Deenadayalan , Reddy Gautama , Barros Daniel Ferreira de , Faria Vinicius Naves Rezende , Shandal Varun , Kurtz Pedro
Published: December 2022

Background Perioperative stroke, delirium, and cognitive impairment could be related to management and to variations in blood pressure control, cerebral hypoperfusion and raised blood volume. Cerebral autoregulation (CAR) is a mechanism to maintain cerebral perfusion through the control of the vascular tone and hemodynamic reactions in the circulation.

Objective The present systematic review addresses the relationship between impaired CAR and perioperative stroke by evaluating the rate of neurological complications after surgery in studies in which perioperative CAR was tested or monitored.

Methods We included randomized clinical trials and prospective observational studies. All studies had adjusted the relative risk, hazard ratio or 95% confidence interval (95%CI) values. These estimation effects were tested using random-effects models. Heterogeneity among the selected studies was assessed using the Higgins and Thompson I2 statistics.

Results The Web of Science, PubMed and EMBASE electronic databases were searched to retrieve articles. A total of 4,476 studies published between 1983 and 2019 were analyzed, but only 5 qualified for the data extraction and were included in the final analysis. The combined study cohort comprised 941 patients who underwent CAR monitoring during surgical procedures. All studies provided information about perioperative stroke, which equated to 16% (158 of 941) of the overall patient population.

Conclusion The present meta-analysis showed evidence of the impact of CAR impairment in the risk of perioperative stroke. On the pooled analysis, blood fluctuations or other brain insults large enough to compromise CAR were associated with the outcome of stroke (odds ratio [OR]: 2.26; 95%CI: 1.54–2.98; p < 0.0001).
Patient Satisfaction with Pisiform Excision for Pisotriquetral Instability or Arthritis: A Prospective Review
Authors: Peters Mikaela J. , Mazor Avi , Glaris Zafeiria , Goetz Thomas Joseph
Published: December 2022

Background Pisotriquetral pain and instability is an elusive cause of ulnar-sided wrist pain. Initial treatment of chronic pisotriquetral pathology should involve a trial of nonoperative therapy such as neutral wrist splint, anti-inflammatories, and intra-articular steroid injections. The mainstay of surgical management of pisotriquetral pain is pisiform excision.

Purpose This prospective study seeks to understand patient satisfaction after pisiform excision in patients with isolated pisotriquetral pathology.

Patients and Methods A consecutive series of nine cases of pisiform excision was performed by the senior surgeon. The primary outcome measure was determined a priori to be the Patient-Rated Wrist Evaluation (PRWE) score. Wrist range of motion, grip strength, and QuickDASH (shortened version of Disabilities of the Arm, Shoulder and Hand) scores were also collected preoperatively and at 3 and 12 months postoperatively as secondary outcome measures.

Results There was a very rapid improvement in the PRWE by 3 months, which was maintained at 12 months. The QuickDASH score was slower to improve, with a significant improvement by 12 months. There was no change in grip strength or wrist range of motion at any time point.

Conclusion Pisiform excision results in a very rapid improvement of symptoms and should be considered in cases of pisotriquetral instability or arthritis that fail conservative management.

Level of Evidence Level IV, case series.
Storage and purification adaptations for the isolation of total RNA from the dura mater
Authors: Ferreira Maria Rosana de Souza , Galvão André Pukey Oliveira , Valença Marcelo Moraes , Martins Danyelly Bruneska Gondim
Published: December 2022

Background RNA extraction is a step that precedes several molecular techniques. The fibrous tissue, more specifically the dura mater, has several limitations in routine protocols, and lacks optimization protocols to overcome these problems.

Objective To test stock reagents and purification kits, optimizing commercial kit protocols for RNA extraction from the dura mater.

Methods Dura mater samples were obtained from eight Wistar rats and maintained in two different stabilizers. The samples were purified using four different protocols, and the RNA was evaluated for the yield and purity in NanoDrop 2000 (Thermo Scientific, Wilmington, DE, United States). Beta-actin gene was used for analyzing gene expression, since is one of the most used reference genes.

Results The RNA preservation was similar in both stabilizers. The addition of an incubation step prior the purification protocols allowed better tissue digestion and RNA recovery. The RNA purified using the protocols membrane-based showed higher quality than liquid-liquid purification. This impact was observed in the 3-week evaluation using RT-qPCR.

Conclusion Stabilizers are efficient for RNA preservation and membrane-based purification protocols are more suitable for RNA recovery from dura mater tissue, allowing the evaluation of gene expression in this type of tissue. Adaptations in the dura mater RNA extraction protocol differ from the pre-established protocols because it takes into account the peculiarity of fibrous tissue and low cellularity. In addition to providing a low-cost mechanism, based on techniques that are part of the laboratory routine, it is possible to improve the quality of the extracted material, ensuring greater efficiency in the use of subsequent techniques.