bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Dosage on a Mindfulness Intervention With First-Year College Students
Authors: Bambacus Elizabeth S. , Conley Abigail H.
Published: September 2021

While mindfulness intervention research is prevalent, it is limited in (1) relation to college students’ grade point average (GPA) and retention and (2) minimum dosage recommended for the intervention. This repeated-measures quasi-experimental nonequivalent control groups study investigated differences in mindfulness, stress, flourishing, GPA, and retention between students ( n = 248) in first-year experience seminars who received a brief mindfulness intervention and the comparison group ( n = 125) who did not receive the intervention. The intervention consisted of three- to five-minute mindfulness exercises at the beginning of class that met once a week. In contrast to results of previous studies, this study—when controlling for class sections and gender—showed no significant differences in any outcome variable between groups. These results provide important evidence that a mindfulness dosing limit might exist. A post hoc binary logistic regression supported previous findings that GPA predicts retention. Implications are discussed in regard to college administrators, faculty, and student affairs professionals.
Axillary pullout syndrome: A novel approach to managing a devastating complication
Authors: Kugler Nathan W , Lewis Brian D , Malinowski Michael
Published: September 2021

Objectives

Axillary pullout syndrome is a complex, potentially fatal complication following axillary-femoral bypass graft creation. The re-operative nature, in addition to ongoing hemorrhage, makes for a complicated and potentially morbid repair.

Methods

We present the case of a 57-year-old man with history of a previous left axillary-femoral-femoral bypass who presented with acute limb-threatening ischemia as a result of bypass thrombosis managed with a right axillary-femoral bypass for limb salvage. His postoperative course was complicated by an axillary anastomotic dehiscence while recovering in inpatient rehabilitation resulting in acute, life-threatening hemorrhage. He was managed utilizing a novel hybrid approach in which a retrograde stent graft was initially placed across the anastomotic dehiscence for control of hemorrhage. He then underwent exploration, decompression, and interposition graft repair utilizing the newly placed stent graft to reinforce the redo axillary anastomosis.

Results and Conclusion

Compared with a traditional operative approach, the hybrid endovascular and open approach limited ongoing hemorrhage while providing a more stable platform for repair and graft revascularization. A hybrid approach to the management of axillary pullout syndrome provides a safe, effective means to the management of axillary anastomotic dehiscence while minimizing the morbidity of ongoing hemorrhage.
Development of an ergonomic wearable robotic device for assisting manual workers
Authors: Yin Peng , Yang Liang , Qu Shengguan
Published: September 2021

Sometimes the automation equipment cannot solve all the problems for industrial enterprises, and human workers cannot be replaced by machines in production activities. The possibility that the workers develop work-related musculoskeletal disorders, while performing high intensity and repetitive installation and commissioning work over a long period of time, is very high. A mechanical design of a passive upper extremities exoskeleton suit to reduce the muscles effort of upper limbs is proposed in this article. Thereby, a decrease in the work-related musculoskeletal disorders risk is expected. To evaluate the ergonomic contribution of the passive upper extremities exoskeleton suit, both static and dynamic tool lift experiments were designed, in which 10 volunteers were asked to participate in the experiments. The surface electromyography is captured from these volunteers to measure the magnitude of muscle output forces that are applied with and then without passive upper extremities exoskeleton suit assistance during the process of manual handling, and the tests are collected for comparison. Results show that there is a significant decrease in the output force and fatigue in deltoid, biceps brachii, and brachioradiali, especially in biceps brachial which is up to 67.8%. The implementation of passive upper extremities exoskeleton suit is not only a benefit to reduce workers’ upper extremities fatigue but also ultimately increase the work efficiency by minimizing work-related musculoskeletal disorders and safety accidents.
Reliability evaluation of m-consecutive- k, l-out-of-n: F system subjected to shocks
Authors: Özbey Fahrettin
Published: September 2021

In this paper, we propose a shock model for an m-consecutive- k, l-out-of- n: F system. This paper presents a reliability analysis of an m-consecutive- k, l-out-of- n: F system subjected to shocks that destroy a random number of components. One of the main random variables is the number of components affected by successive shocks. Phase-type distributions have been used to model the intervals between successive shocks. The main objective of this study is to show how phase-type distributions can be used to determine the reliability of m-consecutive- k, l-out-of- n: F systems subjected to shocks, which destroy a random number of components. Consideration is given to the optimal replacement time problem, which addresses the minimization of the total long-run average cost per unit time.
Prunin modulates the Expression of Cerebral Serotonin Induced by Anxiety-Like Behavior in Mice
Authors: Guo Feng , Yan Dongtao , Qin Zifu , Bais Souravh
Published: September 2021

Anxiety is a state that becomesa disorder when a person experiences disproportionate levels of anxiety on a regular basis. This disproportion is also accompanied by excessive nervousness and fear. This study aimed to determine the protective effect of prunin using different anxiety models. Three preclinical anxiety models, elevated plus maze, light/dark, and social interaction, were employed in the study. Albino mice were selected and treated with pruninand other drugs for 7 days to determine their anti-anxiety effect. Thereafter, their behavior was examined using the plus maze, light-dark chamber, and other stimulatory parameters, such asimmobility, sniffing, and crawling during experimentation. Two doses (50 mg/kg and 100 mg/kg, p.o.) of prunin were administered to two separate mice groups. Further, fluoxetine (10 mg/kg; p.o.) was administered to one of the mice groups for 7 days. Thereafter, the levels of neurotransmitters, such as serotonin and GABA, in brain samples were determined. Based on the results, prunin significantly improved the behavior and mobility of animals in all three anxiety models. Further, prunin modulated the release of serotonin and GABA, demonstrating the mechanistic approach it employs to interact with cellular receptors to mimic neurotransmission. The mRNA expression levels of tph2 (5-HT synthesizing enzyme) and slc6a4 (5-HT transporter) were also found to be downregulated in both prunin- and fluoxetine-treated mice brains. Collectively, our findings suggest that prunin could be administered to treat anxiety in mice. However, further studies should be carried out to explore its potential for clinical application.
Aggressive primary sinonasal Ewing sarcoma with intraorbital and intracranial extension
Authors: Ahmad Kailani Abdul Azim Al-Abrar , Abdullah Baharudin , Yunus Dahziela , Hussain Faezahtul Arbaeyah , Mohamad Sakinah
Published: September 2021

Ewing sarcoma (ES) of the extraskeletal form is a rare occurrence and even rarer to manifest in the sinonasal tract. We describe a case of an advanced sinonasal ES with orbital and intracranial extension that was managed with chemotherapy and endoscopic surgery. Despite completing chemotherapy and surgical resection, the tumor progressed rapidly even before postoperative radiotherapy, and subsequently, she succumbed to death due to sepsis. We would like to discuss the management challenges, pitfalls, and surgical approach which may improve the outcome of this complicated disease.
Use and performance of machine learning models for type 2 diabetes prediction in clinical and community care settings: Protocol for a systematic review and meta-analysis of predictive modeling studies
Authors: De Silva Kushan , Enticott Joanne , Barton Christopher , Forbes Andrew , Saha Sajal , Nikam Rujuta
Published: September 2021

Objective

Machine learning involves the use of algorithms without explicit instructions. Of late, machine learning models have been widely applied for the prediction of type 2 diabetes. However, no evidence synthesis of the performance of these prediction models of type 2 diabetes is available. We aim to identify machine learning prediction models for type 2 diabetes in clinical and community care settings and determine their predictive performance.

Methods

The systematic review of English language machine learning predictive modeling studies in 12 databases will be conducted. Studies predicting type 2 diabetes in predefined clinical or community settings are eligible. Standard CHARMS and TRIPOD guidelines will guide data extraction. Methodological quality will be assessed using a predefined risk of bias assessment tool. The extent of validation will be categorized by Reilly–Evans levels. Primary outcomes include model performance metrics of discrimination ability, calibration, and classification accuracy. Secondary outcomes include candidate predictors, algorithms used, level of validation, and intended use of models. The random-effects meta-analysis of c-indices will be performed to evaluate discrimination abilities. The c-indices will be pooled per prediction model, per model type, and per algorithm. Publication bias will be assessed through funnel plots and regression tests. Sensitivity analysis will be conducted to estimate the effects of study quality and missing data on primary outcome. The sources of heterogeneity will be assessed through meta-regression. Subgroup analyses will be performed for primary outcomes.

Ethics and dissemination

No ethics approval is required, as no primary or personal data are collected. Findings will be disseminated through scientific sessions and peer-reviewed journals.

PROSPERO registration number

CRD42019130886
Becoming Your “Authentic” Self: How Social Media Influences Youth’s Visual Transitions
Authors: Gorea Michelle
Published: September 2021

By focusing attention on the ways that the media manifold fosters visual practices of presentational work for Generation Z, this article examines the active and relational nature of youth’s engagement with visual self-images during the transition between high school and university. Drawing on in-depth interviews with 35 youth between the ages of 15–22, the analysis examines how the relational contexts of family, school, and peers, alongside the socioeconomic and gendered dimensions of young people’s everyday lives work to shape the different ways that youth engage in visual processes of becoming; in terms of becoming who they are and who they want themselves to be. Findings reveal that although youth’s visual self-performances parallel contemporary theorizations of mediatization, self-identity, and visuality, I argue that more attention should be paid to the nuances of transitional moments among young people, and the precise ways in which they navigate practices of “looking,” which are tightly bound up with heightened expectations around visual performance and projection of the self.
Sharing and Commenting Facilitate Political Learning on Facebook: Evidence From a Two-Wave Panel Study
Authors: Kim Dam Hee , Weeks Brian E. , Lane Daniel S. , Hahn Lauren B. , Kwak Nojin
Published: September 2021

Social media, as sources of political news and sites of political discussion, may be novel environments for political learning. Many early reports, however, failed to find that social media use promotes gains in political knowledge. Prior research has not yet fully explored the possibility based on the communication mediation model that exposure to political information on social media facilitates political expression, which may subsequently encourage political learning. We find support for this mediation model in the context of Facebook by analyzing a two-wave survey prior to the 2016 U.S. presidential election. In particular, sharing and commenting, not liking or opinion posting, may facilitate political knowledge gains.
Analysis of the Maturity Level of Business Processes for Science and Technology Parks
Authors: Correia Ana Maria Magalhães , Veiga Claudimar Pereira da , Senff Carlos Otávio , Duclós Luiz Carlos
Published: September 2021

This research analyzes the maturity level of business processes with the application of the Process and Enterprise Maturity Model (PEMM) in the light of Enterprise Architecture (EA). This is qualitative research, cross-sectional, and in the form of a multiple case study performed in science and technology parks in Brazil. A questionnaire conducted by semi-structured interviews, non-participant observations, and document analysis to gather information on the processes was applied to achieve the proposed objective. The finding revealed that 75% of the analyzed parks show signs that processes’ maturity results in optimal performance (Level 3) and can be integrated with other internal processes, maximizing the performance of these parks. Only one park was at Level 2, indicating that business processes led to better results when implemented from one organization. This study shows that even when enterprise capability is at Level 3, this does not help the process enablers rise from Level 2 to Level 3. This study’s originality lies in its showed that the maturity level of the analyzed parks and in making comparisons to identify discrepancies and future actions, considering their responsibility to transfer knowledge from science and technology institutions to the public and private sector.
Defining Grammatical Difficulty to Make Better Choices about Corrective Feedback: A Meta-Analysis of Persian EFL Learners
Authors: Schenck Andrew
Published: September 2021

Past experimental studies of corrective feedback (CF) have isolated factors like grammatical complexity, learner proficiency, and L1 one by one, carefully designing experiments that eliminate the influence of “extraneous” factors. Because each factor is actually codependent, more holistic study is needed. Eleven studies, all of which had English as a Foreign Language (EFL) learners with a Persian L1 and productive measures of speech or writing, were selected for meta-analytic examination. Results suggest that type of grammatical feature, as well as associated learner variables such as L1 similarity or proficiency, collectively influence the efficacy of different CF types. As variables jointly add to the difficulty of a grammatical feature, CF providing a kind of scaffold, in the form of a written or oral reformulation from the teacher, appears to be the most effective. As grammatical difficulty decreases, learners appear to benefit from CF in which the learner is compelled to self-repair.
The Impact of Social Capital on Residents’ Supportive Attitude to Tourism Development: The Mediation Role of Perception of Justice
Authors: Zhu Lantao , Li Xi , Wang YingChuan
Published: September 2021

Based on social capital theory and fairness theory, the study proposes a residents’ supportive attitudes influencing model, with social capital as the antecedent variable, and the perception of justice as mediator. An empirical research was conducted on residents of three well-known island tourist destinations in Zhejiang Province, China, a total of 620 questionnaires were distributed in the three regions. The results of data analysis show that the perception of distributive justice and procedural justice is positively influenced by social capital; it has a positive impact on distributive fairness and residents’ support. Distributive justice has a positive impact on the supportive attitudes of residents. In addition, the mediation effect of distributive justice and procedural justice between social capital and the supportive attitude of residents has been supported. The theoretical contribution and practical value of this research have also been discussed.
Return-to-Play Times and Player Performance After Medial Collateral Ligament Injury in Elite-Level European Soccer Players
Authors: Lavoie-Gagne Ophelie Z. , Retzky Julia , Diaz Connor C. , Mehta Nabil , Korrapati Avinaash , Forlenza Enrico M. , Knapik Derrick M. , Forsythe Brian
Published: September 2021

Background:

Participation in elite-level soccer predisposes athletes to injuries of the medial collateral ligament (MCL), resulting in variable durations of time lost from sport.

Purpose:

To (1) determine the rate of return to play (RTP) and timing after MCL injuries, (2) investigate MCL reinjury incidence after RTP, and (3) evaluate the long-term effects of MCL injury on future performance.

Study Design:

Descriptive epidemiology study.

Methods:

Using publicly available records, we identified athletes who had sustained MCL injury between 2000 and 2016 across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A). Injured athletes were matched to controls using demographic characteristics and performance metrics from the season before injury. We recorded injury severity, RTP rate, reinjury incidence, player characteristics associated with RTP within 2 seasons of injury, player availability, field time, and performance metrics during the 4 seasons after injury.

Results:

A total of 59 athletes sustained 61 MCL injuries, with 86% (51/59) of injuries classified as moderate to severe and surgical intervention performed in 14% (8/59) of athletes. After injury, athletes missed a median of 33 days (range, 3-259 days) and 4 games (range, 1-30 games). Overall, 71% (42/59) of athletes returned successfully at the same level, with multivariable regression demonstrating no athlete characteristic predictive of RTP. MCL reinjury was reported in 3% (2/59) of athletes. Midfielders demonstrated decreased field time after RTP when compared with controls ( P < .05). No significant differences in player performance for any position were identified out to 4 seasons after injury. Injured athletes had a significantly higher rate of long-term retention ( P < .001).

Conclusion:

MCL injuries resulted in a median loss of 33 days in elite European soccer athletes, with the majority of injuries treated nonoperatively. RTP remained high, and few athletes experienced reinjury. While midfielders demonstrated a significant decrease in field time after RTP, player performance and long-term retention were not compromised. Future studies are warranted to better understand athlete-specific and external variables predictive of MCL injury and reinjury, while evaluating treatment and rehabilitation protocols to minimize time lost and to optimize athlete safety and health.
Educating Pharmacists on the Risks of Strong Opioids With Descriptive and Simulated Experience Risk Formats: A Randomized Controlled Trial
Authors: Wegwarth Odette , Wind Stefan , Goebel Eva , Spies Claudia , Meerpohl Joerg J. , Schmucker Christine , Schulte Erika , Neugebauer Edmund , Hertwig Ralph
Published: September 2021

Objectives. High opioid prescription rates in the United States and Europe suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Findings from cognitive decision science suggest that risk perceptions and behaviors can differ depending on whether people learn about risks by experience or description. This study investigated effects of a descriptive versus an experience-based risk education format on pharmacists’ risk perceptions and counseling behavior in the long-term administration of strong opioids to patients with chronic noncancer pain. Methods. In an exploratory, randomized controlled online trial, 300 German pharmacists were randomly assigned to either a descriptive format (fact box) or a simulated experience format (interactive simulation). Primary Outcome Measures. 1) Objective risk perception, 2) subjective risk perception, and 3) intended and 4) actual counseling behavior. Results. Both risk formats significantly improved pharmacists’ objective risk perception, but pharmacists exposed to the fact box estimated the benefit-harm ratio more accurately than those exposed to the simulation. Both formats proved equally effective in adjusting pharmacists’ subjective risk perception toward a better recognition of opioids’ harms; however, pharmacists receiving the simulation showed a greater change in their actual counseling behavior and higher consistency between their intended and actual counseling than pharmacists receiving the fact box. Conclusion. The simulated experience format was less effective than the descriptive format in improving pharmacists’ objective risk perception, equally effective in motivating pharmacists to counsel patients on less risky treatment alternatives and more effective in changing the reported actual counseling behavior. Implications. These exploratory findings provide important insights into the relevance of the description-experience gap for drug safety and raise questions for future research regarding the specific mechanisms at work.
PEG10 amplification at 7q21.3 potentiates large-cell transformation in cutaneous T-cell lymphoma
Authors: Liu Fengjie , Gao Yumei , Xu Bufang , Xiong Shan , Yi Shengguo , Sun Jingru , Chen Zhuojing , Liu Xiangjun , Li Yingyi , Lin Yuchieh , Wen Yujie , Qin Yao , Yang Shuxia , Li Hang , Tejasvi Trilokraj , Tsoi Lam , Tu Ping , Ren Xianwen , Wang Yang
Published: September 2021

Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, undergo large-cell transformation (LCT) in the late stage, manifesting aggressive behavior, resistance to treatments, and poor prognosis, but the mechanisms involved remain unclear. To identify the molecular driver of LCT, we collected tumor samples from 133 MF patients and performed whole-transcriptome sequencing on 49 advanced-stage MF patients, followed by integrated copy number inference and genomic hybridization. Tumors with LCT showed unique transcriptional programs and enriched expressions of genes at chr7q. Paternally expressed gene 10 (PEG10), an imprinted gene at 7q21.3, was ectopically expressed in malignant T cells from LCT, driven by 7q21.3 amplification. Mechanistically, aberrant PEG10 expression increased cell size, promoted cell proliferation, and conferred treatment resistance by a PEG10/KLF2/NF-κB axis in in vitro and in vivo models. Pharmacologically targeting PEG10 reversed the phenotypes of proliferation and treatment resistance in LCT. Our findings reveal new molecular mechanisms underlying LCT and suggest that PEG10 inhibition may serve as a promising therapeutic approach in late-stage aggressive T-cell lymphoma.
American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation
Authors: Kanter Julie , Liem Robert I. , Bernaudin Françoise , Bolaños-Meade Javier , Fitzhugh Courtney D. , Hankins Jane S. , Murad M. Hassan , Panepinto Julie A. , Rondelli Damiano , Shenoy Shalini , Wagner John , Walters Mark C. , Woolford Teonna , Meerpohl Joerg J. , Tisdale John
Published: September 2021

Background: Sickle cell disease (SCD) is a life-limiting inherited hemoglobinopathy that results in significant complications and affects quality of life. Hematopoietic stem cell transplantation (HSCT) is currently the only curative intervention for SCD; however, guidelines are needed to inform how to apply HSCT in clinical practice.

Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and health professionals in their decisions about HSCT for SCD.

Methods: The multidisciplinary guideline panel formed by ASH included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews (through 2019). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.

Results: The panel agreed on 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT.

Conclusions: The evidence review yielded no randomized controlled clinical trials for HSCT in SCD; therefore, all recommendations are based on very low certainty in the evidence. Key recommendations include considering HSCT for those with neurologic injury or recurrent acute chest syndrome at an early age and to improve nonmyeloablative regimens. Future research should include the development of a robust SCD registry to serve as a comparator for HSCT studies.
Peritransplantation ruxolitinib administration is safe and effective in patients with myelofibrosis: a pilot open-label study
Authors: Ali Haris , Tsai Ni-Chun , Synold Timothy , Mokhtari Sally , Tsia Weimin , Palmer Joycelynne , Stiller Tracey , Al Malki Monzr , Aldoss Ibrahim , Salhotra Amandeep , Rahmanuddin Syed , Pullarkat Vinod , Cai Ji-Lian , Stein Anthony , Forman Stephen J. , Marcucci Guido , Mei Matthew , Snyder David S. , Nakamura Ryotaro
Published: September 2021

We report results of our prospective pilot trial evaluating safety/feasibility of peritransplantation ruxolitinib for myelofibrosis treatment. Primary objectives were to determine safety and maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was administered at 2 dose levels (DLs) of 5 and 10 mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus graft-versus-host disease (GVHD) prophylaxis. We enrolled 6 and 12 patients at DL1 and DL2, respectively. Median age at transplantation was 65 years (range, 25-73). Per Dynamic International Prognostic Scoring System, 4 patients were high and 14 intermediate risk. Peripheral blood stem cells were graft source from matched sibling (n = 5) or unrelated (n = 13) donor. At each DL, 1 patient developed dose-limiting toxicities (DLTs): grade 3 cardiac and gastrointestinal with grade 4 pulmonary DLTs in DL1, and grade 3 kidney injury in DL2. All patients achieved engraftment. Grade 2 to 4 and 3 to 4 acute GVHD cumulative incidence was 17% (95% confidence interval [CI], 6-47) and 11% (95% CI, 3-41), respectively. Cumulative incidence of 1-year chronic GVHD was 42% (95% CI, 24-74). With 22.6-month (range, 6.2-25.8) median follow-up in surviving patients, 1-year overall and progression-free survival were 77% (95% CI, 50-91) and 71% (95% CI, 44-87), respectively. Causes of death (n = 4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results show peritransplantation ruxolitinib is safe and well tolerated at MTD of 10 mg twice daily and associated with dose-dependent pharmacokinetic and cytokine profile. Early efficacy data are highly promising in high-risk older patients with myelofibrosis. This trial was registered at www.clinicaltrials.gov as #NCT02917096.
Bilineal evolution of a U2AF1-mutated clone associated with acquisition of distinct secondary mutations
Authors: Montgomery Nathan D. , Galeotti Jonathan , Johnson Steven M. , Commander Leah , Weimer Eric T. , Chandra Pranil K. , Nazir Tariq , Alexander Thomas B. , Zeidner Joshua F. , Foster Matthew C.
Published: September 2021

Rare hematologic malignancies display evidence of both myeloid and lymphoid differentiation. Here, we describe such a novel bilineal event discovered in an adult woman with B-lymphoblastic leukemia (BLL). At the time of BLL diagnosis, the patient had a normal karyotype and a bulk sequencing panel identified pathogenic variants in BCOR, EZH2, RUNX1, and U2AF1, a genotype more typical of myeloid neoplasia. Additionally, the patient was noted to have 3-year history of cytopenias, and morphologic dyspoiesis was noted on post-treatment samples, raising the possibility of an antecedent hematologic disorder. To investigate the clonal architecture of her disease, we performed targeted sequencing on fractionated samples enriched for either B-lymphoblasts or circulating granulocytes. These studies revealed a truncal founder mutation in the spliceosome gene U2AF1 in both fractions, while distinct secondary mutations were present only in B-lymphoblasts (BCOR, NRAS) or myeloid cells (ASXL1, EZH2, RUNX1). These results indicate that both processes evolved from a common U2AF1-mutated precursor, which then acquired additional mutations during a process of divergent evolution and bilineal differentiation. Our findings highlight an atypical mechanism of BLL leukemogenesis and demonstrate the potential utility of fractionated sequencing in the characterization of acute leukemia.
PD-1 inhibition in advanced myeloproliferative neoplasms
Authors: Hobbs Gabriela , Cimen Bozkus Cansu , Moshier Erin , Dougherty Mikaela , Bar-Natan Michal , Sandy Lonette , Johnson Kathryn , Foster Julia Elise , Som Tina , Macrae Molly , Marble Hetal , Salama Mohamed , El Jamal Siraj M. , Zubizarreta Nicole , Wadleigh Martha , Stone Richard , Bhardwaj Nina , Iancu-Rubin Camelia , Mascarenhas John
Published: September 2021

Myelofibrosis (MF) is a clonal stem cell neoplasm characterized by abnormal JAK-STAT signaling, chronic inflammation, cytopenias, and risk of transformation to acute leukemia. Despite improvements in the therapeutic options for patients with MF, allogeneic hematopoietic stem cell transplantation remains the only curative treatment. We previously demonstrated multiple immunosuppressive mechanisms in patients with MF, including increased expression of programmed cell death protein 1 (PD-1) on T cells compared with healthy controls. Therefore, we conducted a multicenter, open-label, phase 2, single-arm study of pembrolizumab in patients with Dynamic International Prognostic Scoring System category of intermediate-2 or greater primary, post-essential thrombocythemia or post-polycythemia vera myelofibrosis that were ineligible for or were previously treated with ruxolitinib. The study followed a Simon 2-stage design and enrolled a total of 10 patients, 5 of whom had JAK2V617mutation, 2 had CALR mutation, and 6 had additional mutations. Most patients were previously treated with ruxolitinib. Pembrolizumab treatment was well tolerated, but there were no objective clinical responses, so the study closed after the first stage was completed. However, immune profiling by flow cytometry, T-cell receptor sequencing, and plasma proteomics demonstrated changes in the immune milieu of patients, which suggested improved T-cell responses that can potentially favor antitumor immunity. The fact that these changes were not reflected in a clinical response strongly suggests that combination immunotherapeutic approaches rather than monotherapy may be necessary to reverse the multifactorial mechanisms of immune suppression in myeloproliferative neoplasms. This trial was registered at www.clinicaltrials.gov as #NCT03065400.
Role of long non-coding RNA H19 in the development of osteoporosis
Authors: Chen Senxiang , Liu Da , Zhou Zimo , Qin Sen
Published: September 2021

Background

Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example.

Results

A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis.

Conclusion

The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.
Virulence factors in multidrug (MDR) and Pan-drug resistant (XDR) Pseudomonas aeruginosa: a cross-sectional study of isolates recovered from ocular infections in a high-incidence setting in southern India
Authors: Naik Poonam , Pandey Suchita , Gagan Satyashree , Biswas Sudeshna , Joseph Joveeta
Published: September 2021

Background

Global concerns have been raised due to upward trend of Multi-drug Resistant (MDR) Pseudomonas aeruginosa reports in ocular infections. Our aim was to characterize the virulence determinants of MDR P. aeruginosa causing ocular infections.

Methods

P. aeruginosa strains were isolated from 46 patients with conjunctivitis (2), endophthalmitis (11) and active keratitis (25) seen at our Institute, between 2016 and 2020. The isolates were identified by Vitek-2 and characterized based on growth kinetics, biofilm formation, motility, pyoverdine and pyocyanin production, phospholipase and catalase activity, urease production along with expression of exotoxins (exo-A, exo-U and exo-S) and correlated to its antibiotic profiles.

Results

Of the 46 P. aeruginosa isolates, 23 were MDR and were significantly (p = 0.03) associated with older (> 65) patients, along with higher production of pyoverdine (58.3%), pyocyanin (30.4%), phospholipase (91.6%) and protease (62.5%) activity, formed strong biofilms and exo-A (30.4%). No significant relation between motility, urease and catalase production with antibiotic susceptibility was observed. Heatmap and PCoA analysis confirmed this unique virulence profile associated with MDR-PA strains.

Conclusion

Phenotypic characteristics of P.aeruginosa might be responsible for increased colonization and antibiotic resistance observed in vivo and understanding these differences may lead to development of clinical guidelines for the management of MDR infections.
Grazing intensity changed the activities of nitrogen assimilation related enzymes in desert Steppe Plants
Authors: Zhu Aimin , Liu Haili , Wang Yuehua , Sun Hailian , Han Guodong
Published: September 2021

Background

Nitrogen, as a limiting factor for net primary productivity in grassland ecosystems, is an important link in material cycles in grassland ecosystems. However, the nitrogen assimilation efficiency and mechanisms of grassland plants under grazing disturbance are still unclear. This study investigated Stipa breviflora desert steppe which had been grazed for 17 years and sampled the root system and leaf of the constructive species Stipa breviflora during the peak growing season under no grazing, light grazing, moderate grazing and heavy grazing treatments. The activities of enzymes related to nitrogen assimilation in roots and leaves were measured.

Results

Compared with no grazing, light grazing and moderate grazing significantly increased the activities of nitrate reductase (NR), glutamine synthetase (GS), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) in leaves, and GS, GOT and GPT in roots of Stipa breviflora, while heavy grazing significantly decreased the activities of GS in leaves and NR in roots of Stipa breviflora. NR, GOT and GPT activities in leaves and roots of Stipa breviflora were positively correlated with nitrogen content, soluble protein, free amino acid and nitrate content.

Conclusions

Grazing disturbance changed the activities of nitrogen assimilation related enzymes of grassland plants, and emphasized that light grazing and moderate grazing were beneficial for nitrogen assimilation by grassland plants. Therefore, establishing appropriate stocking rates is of great significance for material flows in this grassland ecosystem and for the stability and sustainable utilization of grassland resources.
Optimal dose of perineural dexmedetomidine to prolong analgesia after brachial plexus blockade: a systematic review and Meta-analysis of 57 randomized clinical trials
Authors: Cai Hai , Fan Xing , Feng Pengjiu , Wang Xiaogang , Xie Yubo
Published: September 2021

Background and Objectives

Peripheral injection of dexmedetomidine (DEX) has been widely used in regional anesthesia to prolong the duration of analgesia. However, the optimal perineural dose of DEX is still uncertain. It is important to elucidate this characteristic because DEX may cause dose-dependent complications. The aim of this meta-analysis was to determine the optimal dose of perineural DEX for prolonged analgesia after brachial plexus block (BPB) in adult patients undergoing upper limb surgery.

Method

A search strategy was created to identify suitable randomized clinical trials (RCTs) in Embase, PubMed and The Cochrane Library from inception date to Jan, 2021. All adult patients undergoing upper limb surgery under BPB were eligible. The RCTs comparing DEX as an adjuvant to local anesthetic (LA) with LA alone for BPB were included. The primary outcome was duration of analgesia for perineural DEX. Secondary outcomes included visual analog scale (VAS) in 12 and 24 h, consumption of analgesics in 24 h, and adverse events.

Results

Fifty-seven RCTs, including 3332 patients, were identified. The subgroup analyses and regression analyses revealed that perineural DEX dose of 30-50 μg is an appropriate dosage. With short−/intermediate-acting LAs, the mean difference (95% confidence interval [CI]) of analgesia duration with less than and more than 60 μg doses was 220.31 (153.13–287.48) minutes and 68.01 (36.37–99.66) minutes, respectively. With long-acting LAs, the mean differences (95% CI) with less than and more than 60 μg doses were 332.45 (288.43–376.48) minutes and 284.85 (220.31–349.39) minutes.

Conclusion

30-50 μg DEX as adjuvant can provides a longer analgesic time compared to LA alone and it did not increase the risk of bradycardia and hypotension.
Development and validation of nomogram to predict severe illness requiring intensive care follow up in hospitalized COVID-19 cases
Authors: Guner Rahmet , Kayaaslan Bircan , Hasanoglu Imran , Aypak Adalet , Bodur Hurrem , Ates Ihsan , Akinci Esragul , Erdem Deniz , Eser Fatma , Izdes Seval , Kalem Ayse Kaya , Bastug Aliye , Karalezli Aysegul , Surel Aziz Ahmet , Ayhan Muge , Karaahmetoglu Selma , Turan Isıl Ozkocak , Arguder Emine , Ozdemir Burcu , Mutlu Mehmet Nevzat , Bilir Yesim Aybar , Sarıcaoglu Elif Mukime , Gokcinar Derya , Gunay Sibel , Dinc Bedia , Gemcioglu Emin , Bilmez Ruveyda , Aydos Omer , Asilturk Dilek , Inan Osman , Buzgan Turan
Published: September 2021

Background

Early identification of severe COVID-19 patients who will need intensive care unit (ICU) follow-up and providing rapid, aggressive supportive care may reduce mortality and provide optimal use of medical resources. We aimed to develop and validate a nomogram to predict severe COVID-19 cases that would need ICU follow-up based on available and accessible patient values.

Methods

Patients hospitalized with laboratory-confirmed COVID-19 between March 15, 2020, and June 15, 2020, were enrolled in this retrospective study with 35 variables obtained upon admission considered. Univariate and multivariable logistic regression models were constructed to select potential predictive parameters using 1000 bootstrap samples. Afterward, a nomogram was developed with 5 variables selected from multivariable analysis. The nomogram model was evaluated by Area Under the Curve (AUC) and bias-corrected Harrell's C-index with 95% confidence interval, Hosmer–Lemeshow Goodness-of-fit test, and calibration curve analysis.

Results

Out of a total of 1022 patients, 686 cases without missing data were used to construct the nomogram. Of the 686, 104 needed ICU follow-up. The final model includes oxygen saturation, CRP, PCT, LDH, troponin as independent factors for the prediction of need for ICU admission. The model has good predictive power with an AUC of 0.93 (0.902–0.950) and a bias-corrected Harrell's C-index of 0.91 (0.899–0.947). Hosmer–Lemeshow test p-value was 0.826 and the model is well-calibrated (p = 0.1703).

Conclusion

We developed a simple, accessible, easy-to-use nomogram with good distinctive power for severe illness requiring ICU follow-up. Clinicians can easily predict the course of COVID-19 and decide the procedure and facility of further follow-up by using clinical and laboratory values of patients available upon admission.
An automated liver segmentation in liver iron concentration map using fuzzy c-means clustering combined with anatomical landmark data
Authors: Wantanajittikul Kittichai , Saiviroonporn Pairash , Saekho Suwit , Krittayaphong Rungroj , Viprakasit Vip
Published: September 2021

Background

To estimate median liver iron concentration (LIC) calculated from magnetic resonance imaging, excluded vessels of the liver parenchyma region were defined manually. Previous works proposed the automated method for excluding vessels from the liver region. However, only user-defined liver region remained a manual process. Therefore, this work aimed to develop an automated liver region segmentation technique to automate the whole process of median LIC calculation.

Methods

553 MR examinations from 471 thalassemia major patients were used in this study. LIC maps (in mg/g dry weight) were calculated and used as the input of segmentation procedures. Anatomical landmark data were detected and used to restrict ROI. After that, the liver region was segmented using fuzzy c-means clustering and reduced segmentation errors by morphological processes. According to the clinical application, erosion with a suitable size of the structuring element was applied to reduce the segmented liver region to avoid uncertainty around the edge of the liver. The segmentation results were evaluated by comparing with manual segmentation performed by a board-certified radiologist.

Results

The proposed method was able to produce a good grade output in approximately 81% of all data. Approximately 11% of all data required an easy modification step. The rest of the output, approximately 8%, was an unsuccessful grade and required manual intervention by a user. For the evaluation matrices, percent dice similarity coefficient (%DSC) was in the range 86–92, percent Jaccard index (%JC) was 78–86, and Hausdorff distance (H) was 14–28 mm, respectively. In this study, percent false positive (%FP) and percent false negative (%FN) were applied to evaluate under- and over-segmentation that other evaluation matrices could not handle. The average of operation times could be reduced from 10 s per case using traditional method, to 1.5 s per case using our proposed method.

Conclusion

The experimental results showed that the proposed method provided an effective automated liver segmentation technique, which can be applied clinically for automated median LIC calculation in thalassemia major patients.
Multiparametric MRI analysis for the evaluation of renal function in patients with hyperuricemia: a preliminary study
Authors: Feng You-Zhen , Dong Xiang-Nan , Lin Qi-Ting , Chen Ping-Kang , Xiong Xiao-Qing , DingKun SiTu , Qian Long , Cheng Zhong-Yuan , Cai Xiang-Ran
Published: September 2021

Background

To investigate the renal dysfunction in patients with hyperuricemia by employing a multiparametric MRI protocol, consisting of quantitative water molecule diffusion, microstructure, microscopic perfusion, and oxygenation measurements in kidneys.

Materials and methods

A total of 48 patients with hyperuricemia (HU) and 22 age-matched healthy control subjects (HC) were enrolled in the study. For each participant, three different functional magnetic resonance imaging (fMRI) sequences were acquired and analyzed, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and blood-oxygen-level-dependent MRI (BOLD). Thereafter, an independent two-samplet-test was applied to discover the significant differences of MRI indices between the hyperuricemia (HU) and HC groups, and the specific potential biomarkers between two subgroups of HU group (asymptomatic hyperuricemia group (AH) and gouty arthritis group (GA)). Further, multivariate logistic regression analyses were performed to classify the AH from the GA group using the MRI indices with significant between-group differences. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was calculated to assess the performance of each MR index for differentiation between the AH and GA groups.

Results

Ten parametric values of the HU group were significantly lower than those of the HC group among the 14 fMRI parameters (P < 0.05). The cortical D, D*, andfvalues and medullary D and R2*values had significant differences between the AH and GA groups (P < 0.05). Combining the cortical D andfvalues and medullary R2* value gave the best diagnostic efficacy, yielding an AUC, sensitivity, and specificity of 0.967 ± 0.022, 91.67%, and 95.83%, respectively.

Conclusions

A multiparametric MR analysis plays an important role in the evaluation of renal dysfunction in hyperuricemia from multiple perspectives. It could be a promising method for noninvasive detection and identification of the early-stage renal damage induced by hyperuricemia.
Covid-19 infection in pregnant women in Dubai: a case-control study
Authors: Hazari Komal Sundeep , Abdeldayem Rasha , Paulose Litty , Kurien Nimmi , Almahloul Zukaa , Mohammad Hozaifah , Elgergawi Taghrid Faek A. , Alkhanbouli Maryam , Mahmoud Khalid , Fazari Atif Bashir , Hassan Amar , Bayoumi Riad
Published: September 2021

Background

Whilst the impact of Covid-19 infection in pregnant women has been examined, there is a scarcity of data on pregnant women in the Middle East. Thus, the aim of this study was to examine the impact of Covid-19 infection on pregnant women in the United Arab Emirates population.

Methods

A case-control study was carried out to compare the clinical course and outcome of pregnancy in 79 pregnant women with Covid-19 and 85 non-pregnant women with Covid-19 admitted to Latifa Hospital in Dubai between March and June 2020.

Results

Although Pregnant women presented with fewer symptoms such as fever, cough, sore throat, and shortness of breath compared to non-pregnant women; yet they ran a much more severe course of illness. On admission, 12/79 (15.2%) Vs 2/85 (2.4%) had a chest radiograph score [on a scale 1-6] of ≥3 (p-value = 0.0039). On discharge, 6/79 (7.6%) Vs 1/85 (1.2%) had a score ≥3 (p-value = 0.0438). They also had much higher levels of laboratory indicators of severity with values above reference ranges for C-Reactive Protein [(28 (38.3%) Vs 13 (17.6%)] with p < 0.004; and for D-dimer [32 (50.8%) Vs 3(6%)]; with p < 0.001. They required more ICU admissions: 10/79 (12.6%) Vs 1/85 (1.2%) with p=0.0036; and suffered more complications: 9/79 (11.4%) Vs 1/85 (1.2%) with p=0.0066; of Covid-19 infection, particularly in late pregnancy.

Conclusions

Pregnant women presented with fewer Covid-19 symptoms but ran a much more severe course of illness compared to non-pregnant women with the disease. They had worse chest radiograph scores and much higher levels of laboratory indicators of disease severity. They had more ICU admissions and suffered more complications of Covid-19 infection, such as risk for miscarriage and preterm deliveries. Pregnancy with Covid-19 infection, could, therefore, be categorised as high-risk pregnancy and requires management by an obstetric and medical multidisciplinary team.