bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interstitial deletions of chromosome 1p: novel 1p31.3p22.2 microdeletion in a newborn with craniosynostosis, coloboma and cleft palate, and review of the genomic and phenotypic profiles
Authors: Serra Gregorio , Antona Vincenzo , Giuffrè Mario , Piro Ettore , Salerno Sergio , Schierz Ingrid Anne Mandy , Corsello Giovanni 
Published: March 2022

AbstractBackgroundRearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynostosis, dysmorphic face, ocular defects, cleft palate, urinary tract anomalies and hand/foot abnormalities.Case presentationHereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype–phenotype correlations.ConclusionsThe results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile.
Prospective preference assessment for the Comparison of Analgesic Regimen Effectiveness and Safety in Surgery (CARES) trial
Authors: Hyung Brian , Bicket Mark C. , Brull Richard , Pazmino-Canizares Janneth , Bozak Didem , Ladha Karim S. 
Published: March 2022

Abstract
Background
Clinical trials face major barriers such as under-enrollment and selective enrollment, which threaten study completion and undermine validity and generalizability. Thus, we conducted a prospective preference assessment (PPA) prior to commencing the Comparison of Analgesic Regimen Effectiveness and Safety in Surgery (CARES) trial—a randomized controlled study comparing the outcomes of managing acute postoperative pain between opioid-sparing and opioid-based therapies. This PPA aimed to (1) determine the patients’ willingness to participate in the CARES trial, (2) identify the areas for improvement, and (3) assess the differences between willing and unwilling patients.

Methods
Patients undergoing elective laparoscopic cholecystectomy were recruited between August 2019 and February 2020 from two academic hospitals. A survey was administered to each patient consisting of (1) a vignette describing the trial, (2) an assessment of the patients’ understanding of the trial, (3) open-ended questions assessing the attitudes towards the trial, and (4) patient-completed questionnaires. Data were analyzed qualitatively with thematic analysis and quantitatively with the Wilcoxon signed-rank and chi-square tests.

Results
Forty-two patients were enrolled and grouped based on the 6-point Likert scale into willing (4–6, 71%) and not willing (1–3, 29%) to participate in the CARES trial. There were no significant differences with respect to all variables: age, education, sex, visible minority status, previous research, previous surgery, regular use of pain medications, surgical concerns, previous discussions on pain management, significant pain within the past 3 months, and significant use of pain medication within the past month. Factors that motivated participation were contributing to scientific research (45%), altruism (29%), and improving personal pain (24%). Common discouraging factors were negative perceptions of opioids (29%), side effects (21%), being blinded to the study medication (21%), and poor pain management (19%).

Conclusions
This PPA revealed that two key discouraging factors for patients were being blinded to the type of pain medication being taken and the potential for poor pain management as a consequence of participation. Modifications to improve patient acceptance of the CARES trial include ensuring sufficient rescue medicine and follow-up visits consistent with current standards of care for all patients, as well as patient education surrounding safe administration and side effects of the study medications.
Methyl-qPCR: a new method to investigate Epstein–Barr virus infection in post-transplant lymphoproliferative diseases
Authors: Borde Chloé , Quignon Frédérique , Amiel Corinne , Gozlan Joël , Marechal Vincent , Brissot Eolia 
Published: March 2022

AbstractEpstein–Barr virus DNA viral load is used as a surrogate marker to start Rituximab in transplant recipients at risk of developing PTLD. However, an elevated EBV DNAemia does not discriminate lymphoproliferation and replication. We designed a new molecular assay (methyl-qPCR) to distinguish methylated versus unmethylated viral genomes. In blood, viral genomes were highly methylated in EBV primary infections, PTLD and 4/5 transplant recipients with high viral load. The only patient with under-methylated EBV genomes did not respond to rituximab. Methyl-qPCR is a convenient method to discriminate between latent and lytic EBV genomes and could be useful in treatment decisions.
Current status of clinical trials assessing mesenchymal stem cell therapy for graft versus host disease: a systematic review
Authors: Li Ying , Hao Jie , Hu Zheng , Yang Yong-Guang , Zhou Qi , Sun Liguang , Wu Jun 
Published: March 2022

Abstract
Background
Graft-versus-host disease (GVHD) is a common fatal complication of hematopoietic stem cell transplantation (HSCT), where steroids are used as a treatment option. However, there are currently no second-line treatments for patients that develop steroid-resistance (SR). Mesenchymal stem cells (MSCs) have immunomodulatory functions and can exert immunosuppressive effects on the inflammatory microenvironment. A large number of in vitro experiments have confirmed that MSCs can significantly inhibit the proliferation or activation of innate and adaptive immune cells. In a mouse model of GVHD, MSCs improved weight loss and increased survival rate. Therefore, there is great promise for the clinical translation of MSCs for the prevention or treatment of GVHD, and several clinical trials have already been conducted to date.

Main body
In this study, we searched multiple databases and found 79 clinical trials involving the use of MSCs to prevent or treat GVHD and summarized the characteristics of these clinical trials, including study design, phase, status, and locations. We analyzed the results of these clinical trials, including the response and survival rates, to enable researchers to obtain a comprehensive understanding of the field’s progress, challenges, limitations, and future development trends. Additionally, factors that might result in inconsistencies in clinical trial results were discussed.

Conclusion
In this study, we attempted to analyze the clinical trials for MSCs in GVHD, identify the most suitable group of patients for MSC therapy, and provide a new perspective for the design of such trials in the future.
Gender differences in cardiometabolic health and disease in a cross-sectional observational obesity study
Authors: Strack Christina , Behrens Gundula , Sag Sabine , Mohr Margareta , Zeller Judith , Lahmann Claas , Hubauer Ute , Loew Thomas , Maier Lars , Fischer Marcus , Baessler Andrea 
Published: March 2022

Abstract
Background
Beyond the degree of adiposity, the pattern of fat distribution has a profound influence on cardiometabolic risk. It is unclear if sex differences in body fat distribution can potentially explain any sex differences in the prevalence of the metabolic syndrome (MetS) and in individual cardiometabolic risk factors among obese men and women.

Methods
In this cross-sectional analysis, 432 persons from the ongoing Obesity Weight Reduction Study (n = 356 obese, ØBMI 41 ± 8 kg/m2, and 76 non-obese, ØBMI 25 ± 3 kg/m2), were included. The relations of sex to MetS prevalence and selected cardiometabolic risk factors were assessed using univariate and multivariate adjusted regression models.

Results
In crude analyses, %fat mass and the fat mass/lean mass ratio were significantly higher in women than in men, regardless of increasing obesity categories, from normal weight to grade-3-obesity. In contrast, markers of abdominal obesity, such as waist circumference and waist-to-hip ratio were higher in men than in women, despite similar BMI. The prevalence of the MetS was higher in obese men than in women (67.6 vs. 45.0%, p < 0.0001), particularly in younger individuals < 40 years (72.5 vs. 36.8%, p < 0.0001), but “metabolically healthy obesity” (BMI ≥ 30, no other NCEP ATPIII MetS component) was more common in women than in men (15.6 vs. 4.1%, p < 0.0001). After adjusting for age, %body fat and height, sex differences were observed for HDL-cholesterol (p < 0.001), triglycerides (p < 0.001), fasting glucose (p = 0.002), insulin and HOMA-IR levels (p < 0.001), ALAT (p < 0.001), adiponectin (p < 0.001), and sE-selectin (p = 0.005). In contrast, crude sex differences in other variables, such as leptin levels (68 ± 4 in obese women vs. 33 ± 2 µg/L in men, p < 0.0001), disappeared after accounting for differences in %body fat (least-squares means of leptin: 52 ± 4 vs. 55 ± 6 µg /L, p = 0.740). A logistic regression model adjusting for age and lifestyle factors revealed a lower risk of having MetS for women as compared to men (OR = 0.38[0.22–0.60]). That risk estimate did not materially alter after adding BMI to the model. In contrast, no statistically significant association between sex and MetS prevalence was observed after adding waist circumference and adiponectin to the model (OR = 1.41[0.59–3.36]).

Conclusions
Different body fat distribution patterns, particularly abdominal adiposity, adiponectin, and related biomarkers, may contribute to sex differences in cardiometabolic risk factors and to the prevalence of the MetS.
Immune mechanisms associated with sex-based differences in severe COVID-19 clinical outcomes
Authors: Arnold Cosby G. , Libby Anne , Vest Alexis , Hopkinson Andrew , Monte Andrew A. 
Published: March 2022

Abstract
Background
Although biological males and females are equally likely to become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), evidence has mounted that males experience higher severity and fatality compared to females.

Main
The objective of this review is to examine the existing literature on biological mechanisms underlying sex-based differences that could contribute to SARS-CoV-2 infection clinical outcomes. Sex-based differences in immunologic response and hormonal expression help explain the differences in coronavirus disease 2019 (COVID-19) outcomes observed in biological males and females. X inactivation facilitates a robust immune response to COVID-19 in females, who demonstrate a more profound antibody response and faster recovery when compared to males. Low testosterone levels also help explain the dysregulated inflammatory response and poor outcomes observed in some males with COVID-19. Gender differences in health expression and behaviors further compound these observed differences.

Conclusion
Understanding the biology of sex-based differences in COVID-19 severity and mortality could help inform preventative measures, treatment decisions, and development of personalized, sex-specific therapies.
Combined utilization of metabolic inhibitors to prevent synergistic multi-species biofilm formation
Authors: Kang Dingrong , Liu Wenzheng , Kakahi Fatemeh Bajoul , Delvigne Frank 
Published: March 2022

AbstractBiofilm is ubiquitous in industrial water systems, causing biofouling and leading to heat transfer efficiency decreases. In particular, multi-species living in biofilms could boost biomass production and enhance treatment resistance. In this study, a total of 37 bacterial strains were isolated from a cooling tower biofilm where acetic acid and propionic acid were detected as the main carbon sources. These isolates mainly belonged to Proteobacteria and Firmicutes, which occupied more than 80% of the total strains according to the 16S rRNA gene amplicon sequencing. Four species (Acinetobacter sp. CTS3, Corynebacterium sp. CTS5, Providencia sp. CTS12, and Pseudomonas sp. CTS17) were observed co-existing in the synthetic medium. Quantitative comparison of biofilm biomass from mono- and multi-species showed a synergistic effect towards biofilm formation among these four species. Three metabolic inhibitors (sulfathiazole, 3-bromopyruvic acid, and 3-nitropropionic acid) were employed to prevent biofilm formation based on their inhibitory effect on corresponding metabolic pathways. All of them displayed evident inhibition profiles to biofilm formation. Notably, combining these three inhibitors possessed a remarkable ability to block the multi-species biofilm development with lower concentrations, suggesting an enhanced effect appeared in simultaneous use. This study demonstrates that combined utilization of metabolic inhibitors is an alternative strategy to prevent multi-species biofilm formation.
Enhancing financial performance of the banks: the role of customer response and operations management
Authors: Enad Osama Mohamed Ahmed , Gerinda Salah Murtada Abdelrahman 
Published: March 2022

AbstractThe current study investigates the relations between the following variables customer response, operations management, and financial performance. The questionnaires were distributed among the board of upper management, middle management, and first-line management in Al-Tadamon Islamic bank in Sudan. Then, the feedbacks were analyzed using SPSS, and the response rate was 77%. The outcomes displayed that, the customer response effect positively operations management and financial performance. Similarly, operations management influences financial performance, but operations management does not mediate the relations between customer response and financial performance.
Client-therapist dyads and therapy outcome: Does sex matching matters? A cross-sectional study
Authors: Schmalbach Ileana , Albani Cornelia , Petrowski Katja , Brähler Elmar 
Published: March 2022

AbstractMatching clients and therapist based on demographic variables might enhance therapeutic outcomes. Even so, research in this field is still inconclusive and not much is known about same-gender client therapist dyads in the context of cognitive behavioral (CBT) and psychodynamic methods. For this purpose, we studied the therapy outcomes of N = 1.212 participants that had received therapy (3 months–6 years) in Germany. The results showed a trend for same-gender client therapist dyads in terms of symptom reduction and quality of life specific to psychodynamic approaches. The latter applied specifically to female client-therapist dyads. On the other hand, this trend was not fully evident for CBT-based therapies. In conclusion, despite the robust sample and observed trends, it is not clear whether matching same gender dyads is advantageous with regards to symptom reduction and quality of life. Regardless, these results are preliminary and further studies are needed in order to find out whether same gender client-therapist dyads enhance therapy outcomes or not.
Subjective perception of life stress events affects long-term pain: the role of resilience
Authors: Kascakova Natalia , Furstova Jana , Trnka Radek , Hasto Jozef , Geckova Andrea Madarasova , Tavel Peter 
Published: March 2022

Abstract
Objective
There is evidence that experiencing childhood trauma and life stressors across the lifespan together with lower resilience is associated with chronic pain-related conditions. The aim of this study was to explore the potential mediating role of resilience in the relationship between childhood trauma and long-term pain and to explore a possible moderating role of serious life stressors in the last year.

Methods
The participants, drawn from a representative sample of citizens of the Czech Republic (n = 1800, mean age: 46.6 years, 48.7% male), were asked to report various long-term pain conditions, childhood trauma (Childhood Trauma Questionnaire, CTQ), life stressors (Life Stressor Checklist Revised, LSC-R) and resilience (Brief Resilience Scale, BRS) in a cross-sectional face-to-face study conducted in 2016. A conditional process SEM model of moderated mediation was performed.

Results
The occurrence of life stress events affecting the participant’s last year moderated the relationship between childhood trauma, resilience and health. In the group of participants who experienced at least one life stress event affecting their last year, resilience fully mediated the effect of past childhood trauma on long-term pain. In participants who did not experience life stressors with an impact on the last year, the direct path from childhood trauma to health through resilience lost its significance.

Conclusion
The subjective meaning of stress events on one’s life has an impact on the trajectory between childhood trauma and health and acts as a moderator. Resilience may buffer the negative effect of trauma on later long-term pain.
Mutational status may supersede tumor size in predicting the presence of aggressive pathologic features in well differentiated thyroid cancer
Authors: Semsar-Kazerooni Koorosh , Morand Grégoire B. , Payne Alexandra E. , da Silva Sabrina D. , Forest Véronique-Isabelle , Hier Michael P. , Pusztaszeri Marc P. , Tamilia Michael , Payne Richard J. 
Published: March 2022

Background In clinical practice, thyroid tumor size plays a critical role in the staging of thyroid malignancies and in the selection of nodules that should undergo ultrasound-guided fine-needle aspiration. Thyroid tumor size is influenced by the elapsed time since the beginning of oncogenesis and by the presence of somatic mutations driving growth, such as BRAF V600E mutations, associated with aggressive phenotypes, and RAS-like mutations, associated with more indolent behavior. Although large nodules are often considered to be more alarming, the true impact of tumor size on prognosis remains controversial. The aim of this study was to assess the relationship between mutational status, tumor size and aggressiveness, with emphasis on BRAF V600E and RAS-like mutations. Method We conducted a multicentric retrospective chart review in Montréal, Canada, of all patients who underwent thyroid surgery between January 2016 and December 2020, with well-differentiated thyroid cancer on final pathology, and who had undergone molecular testing revealing the presence of BRAF V600E mutations or RAS-like mutations ( NRAS, HRAS or KRAS). Results We included 214 cases. There were 117 (54.7%) cases of BRAF V600E and 97 (45.3%) cases of RAS-like mutations. The BRAF V600E group was statistically associated with a smaller mean tumor size when compared with the RAS group of 1.55 cm and 2.04 cm, respectively. In a multivariate model, tumors with BRAF V600E mutations were also more likely to display aggressive pathological features, including extra-thyroidal extension, lymph node metastasis, columnar cell features, tall cell histology, or hobnail histology (OR 26.69; 95% CI 11.15–70.81). In contrast, tumor size was not associated with pathologic aggressive features on multivariate analysis (OR 0.81; 95% CI 0.54–1.22). Conclusion This study demonstrates that thyroid tumors expressing BRAF V600E mutations correlate with aggressive pathologic features more than tumors expressing RAS-like mutations. When comparing tumors with BRAF V600E and RAS-like mutations, the former were found to be smaller. As a result of this finding, this study suggests that molecular alterations may better predict aggressive pathologic features than the size of the tumor. Graphical Abstract
Inhibition of CK2 mitigates Alzheimer’s tau pathology by preventing NR2B synaptic mislocalization
Authors: Marshall Courtney A. , McBride Jennifer D. , Changolkar Lakshmi , Riddle Dawn M. , Trojanowski John Q. , Lee Virginia M.-Y. 
Published: March 2022

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder that exhibits pathological changes in both tau and synaptic function. AD patients display increases in hyperphosphorylated tau and synaptic activity. Previous studies have individually identified the role of NR2B subunit-containing NMDA receptors in AD related synaptic dysfunction and aggregated tau without reconciling the conflicting differences and implications of NR2B expression. Inhibition of extrasynaptically located NR2B mitigates tau pathology in AD models, whereas the inhibition of synaptic NR2B replicates tau-associated hyperactivity. This suggests that a simultaneous increase in extrasynaptic NR2B and decrease in synaptic NR2B may be responsible for tau pathology and synaptic dysfunction, respectively. The synaptic location of NR2B is regulated by casein kinase 2 (CK2), which is highly expressed in AD patients. Here, we used patient brains diagnosed with AD, corticobasal degeneration, progressive supranuclear palsy or Pick’s disease to characterize CK2 expression across these diverse tauopathies. Human derived material was also utilized in conjunction with cultured hippocampal neurons in order to investigate AD-induced changes in NR2B location. We further assessed the therapeutic effect of CK2 inhibition on NR2B synaptic distribution and tau pathology. We found that aberrant expression of CK2, and synaptically translocated NR2B, is unique to AD patients compared to other tauopathies. Increased CK2 was also observed in AD-tau treated neurons in addition to the mislocalization of NR2B receptors. Tau burden was alleviated in vitro by correcting synaptic:extrasynaptic NR2B function. Restoring NR2B physiological expression patterns with CK2 inhibition and inhibiting the function of excessive extrasynaptic NR2B with Memantine both mitigated tau accumulation in vitro. However, the combined pharmacological treatment promoted the aggregation of tau. Our data suggests that the synaptic:extrasynaptic balance of NR2B function regulates AD-tau pathogenesis, and that the inhibition of CK2, and concomitant prevention of NR2B mislocalization, may be a useful therapeutic tool for AD patients.