bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression based molecular test proves clinical validity as diagnostic aid for the differential diagnosis of psoriasis and eczema in formalin fixed and paraffin embedded tissue
Authors: Fischer Felix , Roenneberg Sophie , Graner Larissa , Schlenker Franziska , Zengerle Roland , Theis Fabian J. , Schmidt-Weber Carsten B. , Biedermann Tilo , Lauffer Felix , Garzorz-Stark Natalie , Eyerich Stefanie 
Published: May 2022

AbstractHighly specific and efficient drugs have been developed during the last two decades to treat non-communicable chronic inflammatory skin diseases (ncISD). Due to their specificity, these drugs are asking for precise diagnostic measures to attribute the most efficient treatment to each patient. Diagnosis, however, is complicated by the complex pathogenesis of ncISD and their clinical and histological overlap. Especially, precise diagnosis of psoriasis and eczema is difficult in special cases and molecular diagnostic tools need to be developed to support gold standard diagnosis of patients. In this line, we have developed a real-time based molecular classifier to distinguish psoriasis from eczema in RNA-later fixed skin samples. However, this type of skin sample is not regularly used in routine diagnostics. Therefore, we evaluated if the combination of NOS2 and CCL27 expression in lesional skin can be transferred to formalin-fixed paraffin embedded (FFPE) tissue. We present a FFPE-based molecular classifier (MC) that determines the probability for psoriasis with a specificity and sensitivity of 100% and 92%, respectively, and an area under the curve (AUC) of 0.97 delivering comparable results to the RNA-later based MC. The probability for psoriasis as well as the PCR result of NOS2 expression correlated positive with disease hallmarks of psoriasis and negative with eczema hallmarks. This tool now offers broad usage in pathology laboratories and can support diagnostic decision making on a molecular level.
Risk of Plasmodium vivax recurrences follows a 30-70 rule and indicates relapse heterogeneity in the population
Authors: Stadler Eva , Cromer Deborah , Mehra Somya , Adekunle Adeshina I , Flegg Jennifer A , Anstey Nicholas M , Watson James A , Chu Cindy S , Mueller Ivo , Robinson Leanne J , Schlub Timothy E , Davenport Miles P , Khoury David S 
Published: May 2022

AbstractA key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections, immunity, and transmission intensity. Some of these factors may cause temporary changes in hypnozoite activation over time, leading to ‘temporal heterogeneity’ in reactivation risk. In addition, variation in exposure to infection may be a longer-term characteristic of individuals that leads to ‘population heterogeneity’ in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences.
Opposing and emotion-specific frontal alterations during facial emotion processing in generalized anxiety and depression
Authors: Chen Yuanshu , Liu Congcong , Xin Fei , Haocen Zhou , Huang Yulan , Wang Jinyu , Dai Jing , Zou Zhili , Ferraro Stefania , Kendrick Keith M , Zhou Bo , Xu Xiaolei , Becker Benjamin 
Published: May 2022

AbstractBackgroundMajor depression (MDD) and generalized anxiety disorder (GAD) have become one of the leading global causes of disability and both are characterized by marked interpersonal and social impairments. However, despite a high comorbidity and overlapping social-emotional deficits it remains unclear whether MDD and GAD share a common neural basis during interpersonal processing.MethodsThis study combined an emotional face processing paradigm with fMRI and dimensional and categorical analyses in a sample of unmedicated MDD and GAD patients (N = 72) as well as healthy controls (N = 35).ResultsNo group differences were found in categorical analyses. However, the dimensional analyses revealed that dorsolateral prefrontal cortex (dlPFC) reactivity to sad facial expressions was positively associated with depressive, yet negatively associated with GAD symptom load in the entire sample. On the network level depression symptom load was positively associated with functional connectivity between the bilateral amygdala and a widespread network including the anterior cingulate and insular cortex.LimitationsSex differences were not examined in the present study and some patients exhibited depression-GAD comorbidity.ConclusionsTogether, these findings suggest that the dlPFC - engaged in cognitive and emotional processing - exhibits symptom- and emotion-specific alteration during interpersonal processing. Dysregulated communication between amygdala and core regions of the salience network may represent MDD-specific neural dysregulations.
Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease-2019
Authors: Brown Pierre Antoine , McGuinty Michaeline , Argyropoulos Christos , Clark Edward G , Colantonio David , Giguere Pierre , Hiremath Swapnil 
Published: May 2022

AbstractIntroductionNirmatrelvir/Ritonavir was approved for use in high risk outpatients with coronavirus disease (COVID-19). However, patients with severe chronic kidney disease, including patients on dialysis, were excluded from the phase 3 trial, and currently the drug is not recommended below a glomerular filtration rate of 30 ml/min/1.73m2. Based on available pharmacological data and principles, we developed a modified dose which was lower, and administered at longer intervals.We administered nirmatrelvir/ritonavir as 300/100 mg on day one, followed by 150/100 mg daily from day two to day five. In this case series, we report the initial experience with this modified dose regimen.MethodsThis is a retrospective chart review, conducted after obtaining institutional board approval. Demographic and outcome data was abstracted from the electronic medical record for dialysis patients who developed COVID-19 during the period of study and received nirmatrelvir/ritonavir. The principal outcomes we describe are symptom resolution, and safety data with the modified dose regimen in the dialysis patients.Results19 patients developed COVID-19 during the period of study of whom 15 received nirmatrelvir/ritonavir. 47% of them were female and 67% had diabetes. Most patients had received three doses of the vaccine (80%) while 13% were unvaccinated. Potential drug interactions concerns were common (median 2 drugs per patient) with amlodipine and atorvastatin being the commonest drugs requiring dose modification. Nirmatrelvir/ritonavir use was associated with symptom resolution in all patients, and was well tolerated. One patient had a rebound of symptoms, which improved in 2 more days. There were no COVID-19 related hospitalizations or deaths in any of the patients.ConclusionIn this case series of 15 hemodialysis patients with COVID-19, a modified dose of nirmatrelvir/ritonavir use, with pharmacist support for drug interaction management, was associated with symptom resolution, and was well tolerated with no serious adverse effects.
Changes in immunoglobulin levels during clozapine treatment in schizophrenia
Authors: Griffiths Kira , Mellado Maria Ruiz , Chung Raymond , Lally John , McQueen Grant , Sendt Kyra-Verena , Gillespie Amy , Ibrahim Muhammad , Richter Alex , Shields Adrian , Ponsford Mark , Jolles Stephen , Hodsoll John , Pollak Thomas , Upthegrove Rachel , Egerton Alice , MacCabe James H 
Published: May 2022

ABSTRACTBackgroundClozapine is the only licensed pharmacotherapy for patients with treatment-resistant schizophrenia (TRS), but its use is limited due to adverse effects. Clozapine treatment has been recently associated with reductions in immunoglobulin (Ig) levels cross-sectionally, however prospective studies are required to establish longitudinal effects. This study aimed to determine whether reductions in immunoglobulin levels occur over 6 months after initiating clozapine treatment. An exploratory aim was to investigate relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment.MethodsIn 56 participants with TRS, Ig A, M and G levels were measured in serum using a sandwich immunoassay. Samples for analysis were acquired prior to starting clozapine and at 6, 12 and 24 weeks after initiating clozapine treatment. Clinical symptoms were measured using the positive and negative syndrome scale for schizophrenia (PANSS).ResultsAll three classes of Ig decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: B – 32.7, 95% CI = -61.19, -4.2, p = 0.04; IgG: B – 55.94, 95% CI = -111.03, -0.844, p = 0.05). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: B = -21.73, 95% CI = -37.10, -6.35, p = 0.006; 24 weeks: B = -32.54, 95% CI = -48.89, 16.18, p = 0.0001). Changes in both IgA and IgG were correlated with the percentage change in PANSS total scores over 12 weeks, such that greater reductions in IgA and IgG during clozapine treatment were associated with greater reductions in symptom severity (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.50, p = 0.02)ConclusionsThe observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. The associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.
Are midwives ready to provide quality evidence-based care after pre-service training? Curricula assessment in four countries - Benin, Malawi, Tanzania, and Uganda
Authors: Moller Ann-Beth , Welsh Joanne , Ayebare Elizabeth , Chipeta Effie , Gross Mechthild M , Houngbo Gisele , Hounkpatin Hashim , Kandeya Bianca , Mwilike Beatrice , Nalwadda Gorrette , Petzold Max , Sognonvi Antoinette , Hanson Claudia 
Published: May 2022

AbstractThis research sought to map midwifery pre-service training curricula as part of the Action Leveraging Evidence to Reduce perinatal morTality and morbidity in sub-Saharan Africa (ALERT) project conducted in Benin, Malawi, Tanzania, and Uganda.We conducted the review in two phases. In the first phase, online interviews were performed with the lead project midwives in all four study countries to get an overview of midwifery care providers’ pre-service training courses, registration, and licensing requirements. We performed a mapping review of midwifery care providers’ pre-service training curricula from different training institutions in the four study countries during the second phase.Curricula were reviewed and mapped against the International Confederation of Midwives (ICM) Essential Competencies framework to assess whether these curricula included the minimum essential training components described in the ICM framework.We identified 10 different professional titles for midwifery care providers. The number of years spent in pre-service training varied from one and a half to four years.Ten pre-service curricula were obtained and the assessment revealed that none of the curricula included all ICM competencies. Main gaps identified in all curricula related to women-centred care, inclusion of women in decision making, provision of care to women with unintended or mistimed pregnancy, fundamental human rights of individuals and evidence-based learning.This review suggests that there are skills, knowledge and behaviour gaps in pre-service training curricula for midwifery care providers when mapped to the ICM Essential Competencies framework. These gaps are similar among the different training courses in participating countries. The review also draws attention to the plethora of professional titles and different pre-service training curricula within countries.
Prevalence and demographic distribution associated with pre-eclampsia among pregnant women at a local Teaching Hospital in Ghana
Authors: Adwoa Nyarko , Kunfah Joshua A. , Akayuure Collins Adombine , Kappiah Jamilatu , Kampo Sylvanus 
Published: May 2022

AbstractBackgroundIn sub-Saharan Africa, pre-eclampsia remains a major health problem contributing to high rates of maternal mortality. Despite this condition having adverse effects on maternal and child health, its prevalence and associated risk factors are still significant, especially in developing countries including Ghana. This study aimed to assess the prevalence and demographic distributions associated with pre-eclampsia among pregnant women at the Ho Teaching Hospital.MethodsA facility-based retrospective study was conducted by reviewing available data or hospital records of pregnant mothers who were admitted to the labour and maternity wards from January 2018 to December 2020. The data were collected using a structured checklist.ResultsA total of 5,609 deliveries were recorded from 2018 to 2020. Out of the 5,609 deliveries, 314 pre-eclampsia cases were recorded giving an overall prevalence of 5.6 %. The yearly prevalence for 2018, 2019, and 2020 were 4.6 %, 5.6 %, and 6.6 %, respectively. The most recorded pre-eclampsia cases were seen among women within the age group of 18-24 years. The data showed that 112 (35.7 %) of the mothers who had pre-eclampsia were nulliparous. Pre-eclampsia associated maternal and fetal complications were; preterm delivery 221 (70.4 %), intrauterine fetal death 62 (19.7 %), eclampsia 9 (2.9 %), HELLP syndrome 5 (1.6 %) and maternal death 17 (5.4 %). Associated factors of pre-eclampsia were parity, level of education, and occupation (p=<0.05).ConclusionThe findings of this study showed a rising trend in the incidence of pre-eclampsia over the years at the Ho Teaching Hospital. Parity, level of education, and occupation were found to be associated with developing pre-eclampsia.
The expression of cancer stem cells and its effects on the propensity for recurrence and metastasis in bladder cancer: a systematic review
Authors: Hamid Agus Rizal Ardy Hariandy , Syadza Yasmina Zahra , Yausep Oliver Emmanuel , Indy Christanto Roberto Bagaskara , Muharia Bayu Hernawan Rahmat , Mochtar Chaidir Arif 
Published: May 2022

AbstractBladder cancer is one of the most frequent cancers of the urinary tract, associated with high recurrence rates and metastasis. Cancer stem cells (CSCs) are a subpopulation of cancer cells characterized by high self-renewal and differentiation capacities, resulting in increased cancer recurrence, larger tumor size, higher rates of metastasis, higher resistance to treatment, and overall poorer prognosis. This study aimed to evaluate the role of CSCs as a prognostic tool to predict the risks of metastasis and recurrence in bladder cancer. A literature search was conducted across seven databases from January 2000 to February 2022 for clinical studies investigating the use of CSCs to determine the prognosis of bladder cancer. The following keywords were used: (“Bladder Cancer” OR “Transitional Cell Carcinoma” OR “Urothelial Carcinoma”) AND (“Stem Cell” OR “Stem Gene”) AND (“Metastasis” OR “Recurrence”). A total of 12 studies were deemed eligible for inclusion. SOX2, IGF1R, SOX4, ALDH1, CD44, Cripto-1, OCT4, ARRB1, ARRB2, p-TFCP2L1, CDK1, DCLK1, and NANOG, which were all identified as CSC markers, have been implicated in the recurrence and metastasis of tumor in bladder cancer, which played a role as prognostic factor of bladder cancer. Given the pluripotent and highly proliferative properties of CSCs. CSCs may play a role in the complex biological behavior of bladder cancer, including, but not limited to, its high rates of recurrence, metastasis, and resistance to treatment. The detection of cancer stem cell markers offers a promising approach in determining the prognosis of bladder cancer. Further studies in this area are thus warranted and may contribute significantly to the overall management of bladder cancer.
SARS-CoV-2 infection in vaccinated individuals induces virus-specific nasal resident CD8 and CD4 T cells of broad specificity
Authors: Er Lim Joey Ming , Tan Anthony T. , Le Bert Nina , Hang Shou Kit , Hong Low Jenny Guek , Bertoletti Antonio 
Published: May 2022

AbstractRapid recognition of SARS-CoV-2-infected cells by T cells resident in the upper airway might provide an important layer of protection against COVID-19. Whether parenchymal SARS-CoV-2 vaccination or infection induce nasal resident T cells specific for distinct SARS-CoV-2 proteins is unknown. We collected T cells from the nasal secretion of COVID-19 vaccinees, who either experienced SARS-CoV-2 infection after vaccination (n=20) or not (n=15) and analyzed their phenotype, SARS-CoV-2 specificity and function. Nasal-resident IFN-γ producing SARS-CoV-2-specific CD8 and CD4 T cells were detected exclusively in vaccinees who experienced SARS-CoV-2 breakthrough infection. Importantly, the vaccine priming of Spike-specific T cells does not suppress the induction of CD8 and CD4 T cells specific for different SARS-CoV-2 proteins (i.e. NP and NSP-12) that persisted in the nasal cavity up to 3 months after infection. These data highlight the importance of viral nasal challenge in the formation of SARS-CoV-2 specific antiviral immunity at the site of primary infection and further define the immunological features of SARS-CoV-2 hybrid immunity.
Rapid estimation of cortical neuron activation thresholds by transcranial magnetic stimulation using convolutional neural networks
Authors: Aberra Aman S. , Lopez Adrian , Grill Warren M. , Peterchev Angel V. 
Published: May 2022

AbstractBackgroundTranscranial magnetic stimulation (TMS) can modulate neural activity by evoking action potentials in subpopulations of cortical neurons. The TMS-induced electric field (E-field) can be simulated in subject-specific head models derived from MR images, but the spatial distribution of the E-field alone does not predict the physiological response. Coupling E-field models to populations of biophysically realistic neuron models yields insights into the activation mechanisms of TMS, but the significant computational cost associated with these models limits their use and eventual translation to clinically relevant applications.ObjectiveThe objective was to develop computationally efficient estimators of the activation thresholds of multi-compartmental cortical neuron models in response to TMS-induced E-field distributions.MethodsMulti-scale models combining anatomically accurate finite element method (FEM) simulations of the TMS E-field with layer-specific representations of cortical neurons were used to generate a large dataset of activation thresholds. 3D convolutional neural networks (CNNs) were trained on these data to predict the activation threshold of specific model neurons given the local E-field distribution. Using training and test data from different head models, the CNN estimator was compared to an approach using the uniform E-field approximation to estimate thresholds in the non-uniform TMS-induced E-field.ResultsThe 3D CNNs were more accurate than the uniform E-field approach, with mean absolute percent error (MAPE) on the test dataset below 2.5% compared to 5.9 – 9.8% with the uniform E-field approach. Further, there was a strong correlation between the CNN predicted and actual thresholds for all cell types (R2 > 0.96) compared to the uniform E-field approach (R2 = 0.62 – 0.91). The CNNs estimate thresholds with a 2 – 4 orders of magnitude reduction in the computational cost of the multi-compartmental neuron models.Conclusion3D CNNs can estimate rapidly and accurately the TMS activation thresholds of biophysically realistic neuron models using sparse samples of the local E-field, enabling simulating responses of large neuron populations or parameter space exploration on a personal computer.
Extended practice improves the accuracy and efficiency of goal-directed reaching guided by supplemental kinesthetic vibrotactile feedback
Authors: Shah Valay A , Thomas Ashiya , Mrotek Leigh A , Casadio Maura , Scheidt Robert A 
Published: May 2022

AbstractPrior studies have shown that providing task-specific vibrotactile feedback (VTF) during reaching and stabilizing with the arm can immediately improve the accuracy and efficiency. However, such studies typically evaluate performance after less than 1 hour of practice using VTF. Here we tested the effects of extended practice using supplemental kinesthetic VTF on goal-directed reaching with the arm. Healthy young adults performed a primary reaching task and a secondary choice reaction task individually and as a dual-task. The reaching task was performed under three feedback conditions: visual feedback, proprioceptive feedback, and with supplemental kinesthetic VTF applied to the non-moving arm. We compared performances before, during, and after approximately 10 hours of practice on the VTF-guided reaching task, distributed across 20 practice sessions. Upon initial exposure to VTF-guided reaching, participants were immediately able to use the VTF to improve reaching accuracy. Performance improvements were retained from one practice session to the next. After 10 hours of practice, the accuracy and temporal efficiency of VTF-guided reaching were equivalent to or better than reaching performed without vision or VTF. However, hand paths during VTF-guided reaching exhibited a persistent strategy whereby movements were decomposed into discrete sub-movements along the cardinal axes of the VTF interface. Dual-tasking capability also improved, such that the primary and secondary tasks we performed more concurrently after extended practice. Our results demonstrate that extended practice on VTF-guided reaching can yield performance improvements that accrue in a manner increasingly resistant to dual-task interference.
Developmental Coordination Disorder: What Can We Learn From Recombinant Inbred Mice Using Motor Learning Tasks and Quantitative Trait Locus Analysis
Authors: Gill Kamaldeep , Rajan Soundara Rajan Jeffy , Chow Eric , Ashbrook David G. , Williams Robert W. , Zwicker Jill G. , Goldowitz Daniel 
Published: May 2022

AbstractDevelopmental Coordination Disorder (DCD) is a motor skills disorder that affects 5-6% of all school-aged children. There is an indication that DCD has an underlying genetic component due to its high heritability. Therefore, we we have explored the use of a recombinant inbred family of mice known as the BXD panel to understand the genetic basis of complex traits (i.e., motor learning) through identification of Quantitative Trait Loci (QTLs). The overall aim of this study was to utilize the QTL approach to evaluate the genome-to-phenome correlation in BXD strains of mice in order to to better understanding the human presentation of DCD. Results in this current study indicate there is a spectrum of motor learning in the pre-selected BXD strains of mice with a spectrum between high and low learning capabilities. Five lines – BXD15, BXD27, BXD28, BXD75, and BXD86 – exhibited the most DCD-like phenotype, when compared to other BXD lines of interest. The results indicate that BXD15 and BXD75 struggled primarily with gross motor skills, BXD28 primarily had difficulties with fine motor skills, and BXD27 and BXD28 lines struggled with both fine and gross motor skills. The functional roles of significant QTL genes were assessed in relation to DCD-like behavior. Only Rab3a (Ras-related protein Rab-3A) emerged as a best candidate gene for the horizontal ladder rung task. This gene is found to be associated with brain and skeletal muscle development. This is the first study to specifically examine the genetic linkage of DCD using BXD lines of mice.