bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingolipid lysosomal storage diseases: from bench to bedside
Authors: Abed Rabbo Muna , Khodour Yara , Kaguni Laurie S. , Stiban Johnny 
Published: May 2021

AbstractJohann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.
Construction of nanomaterials as contrast agents or probes for glioma imaging
Authors: Zhao Wei , Yu Xiangrong , Peng Shaojun , Luo Yu , Li Jingchao , Lu Ligong 
Published: May 2021

AbstractMalignant glioma remains incurable largely due to the aggressive and infiltrative nature, as well as the existence of blood–brain-barrier (BBB). Precise diagnosis of glioma, which aims to accurately delineate the tumor boundary for guiding surgical resection and provide reliable feedback of the therapeutic outcomes, is the critical step for successful treatment. Numerous imaging modalities have been developed for the efficient diagnosis of tumors from structural or functional aspects. However, the presence of BBB largely hampers the entrance of contrast agents (Cas) or probes into the brain, rendering the imaging performance highly compromised. The development of nanomaterials provides promising strategies for constructing nano-sized Cas or probes for accurate imaging of glioma owing to the BBB crossing ability and other unique advantages of nanomaterials, such as high loading capacity and stimuli-responsive properties. In this review, the recent progress of nanomaterials applied in single modal imaging modality and multimodal imaging for a comprehensive diagnosis is thoroughly summarized. Finally, the prospects and challenges are offered with the hope for its better development.
Human nuclear receptors (NRs) genes have prognostic significance in hepatocellular carcinoma patients
Authors: Sun Guangtao , Sun Kejian , Shen Chao 
Published: May 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality in the world.

Method
We downloaded the mRNA profiles and clinical information of 371 HCC patients from The Cancer Genome Atlas (TCGA) database. The consensus clustering analysis with the mRNA levels of 48 nuclear receptors (NRs) was performed by the “ConsensusClusterPlus.” The univariate Cox regression analysis was performed to predict the prognostic significance of NRs on HCC. The risk score was calculated by the prognostic model constructed based on eight optimal NRs. Then multivariate Cox regression analysis was performed to determine whether the risk score is an independent prognostic signature. Finally, the nomogram based on multiple independent prognostic factors was used to predict the long-term survival of HCC patients.

Results
The prognostic model constructed based on the eight optimal NRs (NR1H3, ESR1, NR1I2, NR2C1, NR6A1, PPARD, PPARG, and VDR) could effectively predict the prognosis of HCC patients as an independent prognostic signature. Moreover, the nomogram was constructed based on multiple independent prognostic factors including risk score and tumor node metastasis (TNM) stage and could better predict the long-term survival for 3- and 5-year of HCC patients.

Conclusion
Our results provided novel evidences that NRs could act as the potential prognostic signatures for HCC patients.
The utility of self-rated health in population surveys: the role of bodyweight
Authors: Bozick Robert 
Published: May 2021

Abstract
Background
Self-rated health (SRH) is one of the most commonly used summary measures of overall health and well-being available to population scientists due to its ease of administration in large-scale surveys and to its efficacy in predicting mortality. This paper assesses the extent to which SRH is affected by its placement before or after questions about bodyweight on a survey, and whether differences in placement on the questionnaire affects SRH’s predictive validity.

Methods
I assessed the validity of SRH in predicting the risk of mortality by comparing outcomes of sample members who were asked to rate their health before reporting on their bodyweight (the control group) and sample members who were asked to rate their health after reporting on their bodyweight (the treatment group). Both the control and treatment group were randomly assigned via an experiment administered as a module in a nationally representative sample of adults in the USA in 2019 (N = 2523).

Results
The odds of reporting a more favorable appraisal of health are 30% lower for sample members who were in the treatment group when compared with the control group. Additionally, the SRH of treatment group members is significantly associated with their risk of mortality, while the SRH of control group members is not.

Conclusion
The findings from this study suggest that for researchers to maximize the utility of SRH, closer attention needs to be paid to the context of the survey within which it asked. SRH is highly sensitive to the questions that precede it, and this sensitivity may in turn mischaracterize the true health of the population that the survey is intending to measure.
Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer
Authors: Mezynski M. Janusz , Farrelly Angela M. , Cremona Mattia , Carr Aoife , Morgan Clare , Workman Julie , Armstrong Paul , McAuley Jennifer , Madden Stephen , Fay Joanna , Sheehan Katherine M. , Kay Elaine W. , Holohan Ciara , Elamin Yasir , Rafee Shereen , Morris Patrick G. , Breathnach Oscar , Grogan Liam , Hennessy Bryan T. , Toomey Sinead 
Published: May 2021

Abstract
Background
Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in overcoming trastuzumab resistance is unclear.

Methods
Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients. A panel of gastric cell lines (N87, OE19, ESO26, SNU16, KATOIII) were profiled for anti-proliferative response to the PI3K inhibitor copanlisib and the MEK1/2 inhibitor refametinib alone and in combination with anti-HER2 therapies.

Results
Patients with HER2-positive GC had significantly poorer overall survival compared to HER2-negative patients (15.9 months vs. 35.7 months). Mutations in PIK3CA were only identified in HER2-negative tumours, while ERBB-family mutations were identified in HER2-positive and HER2-negative tumours. Copanlisib had anti-proliferative effects in 4/5 cell lines, with IC50s ranging from 23.4 (N87) to 93.8 nM (SNU16). All HER2-positive cell lines except SNU16 were sensitive to lapatinib (IC50s 0.04 µM–1.5 µM). OE19 cells were resistant to trastuzumab. The combination of lapatinib and copanlisib was synergistic in ESO-26 and OE-19 cells (ED50: 0.83 ± 0.19 and 0.88 ± 0.13, respectively) and additive in NCI-N87 cells (ED50:1.01 ± 0.55). The combination of copanlisib and trastuzumab significantly improved growth inhibition compared to either therapy alone in NCI-N87, ESO26 and OE19 cells (p < 0.05).

Conclusions
PI3K or MEK inhibition alone or in combination with anti-HER2 therapy may represent an improved treatment strategy for some patients with HER2-positive GC, and warrants further investigation in a clinical trial setting.
Identifying the functions of two biomarkers in human oligodendrocyte progenitor cell development
Authors: Zhou Haipeng , He Ying , Wang Zhaoyan , Wang Qian , Hu Caiyan , Wang Xiaohua , Lu Siliang , Li Ke , Yang Yinxiang , Luan Zuo 
Published: May 2021

Abstract
Background
Human oligodendrocyte precursor cells (hOPCs) are an important source of myelinating cells for cell transplantation to treat demyelinating diseases. Myelin oligodendrocytes develop from migratory and proliferative hOPCs. It is well known that NG2 and A2B5 are important biological markers of hOPCs. However, the functional differences between the cell populations represented by these two biomarkers have not been well studied in depth.

Objective
To study the difference between NG2 and A2B5 cells in the development of human oligodendrocyte progenitor cells.

Methods
Using cell sorting technology, we obtained NG2+/−, A2B5+/− cells. Further research was then conducted via in vitro cell proliferation and migration assays, single-cell sequencing, mRNA sequencing, and cell transplantation into shiverer mice.

Results
The proportion of PDGFR-α + cells in the negative cell population was higher than that in the positive cell population. The migration ability of the NG2+/−, A2B5+/− cells was inversely proportional to their myelination ability. The migration, proliferation, and myelination capacities of the negative cell population were stronger than those of the positive cell population. The ability of cell migration and proliferation of the four groups of cells from high to low was: A2B5− > NG2− > NG2+ > A2B5+. The content of PDGFR-α+ cells and the ability of cell differentiation from high to low was: NG2− > A2B5− > A2B5+ > NG2+.

Conclusion
In summary, NG2+  and A2B5+ cells have poor myelination ability due to low levels of PDGFR-α+ cells. Therefore, hOPCs with a higher content of PDGFR-α+ cells may have a better effect in the cell transplantation treatment of demyelinating diseases.
Electronic forms for patient reported outcome measures (PROMs) are an effective, time-efficient, and cost-minimizing alternative to paper forms
Authors: Yu Jennifer Y. , Goldberg Talia , Lao Nicholas , Feldman Brian M. , Goh Y. Ingrid 
Published: May 2021

Abstract
Background
Patient reported outcome measures (PROMs) provide valuable insight on patients’ well-being and facilitates communication between healthcare providers and their patients. The increased integration of the technology within the healthcare setting presents the opportunity to collect PROMs electronically, rather than on paper. The Childhood Health Assessment Questionnaire (CHAQ) and Quality of My Life (QoML) are common PROMs collected from pediatric rheumatology patients. The objectives of this study are to (a) determine the equivalence of the paper and electronic forms (e-form) of CHAQ and QoML questionnaires; (b) identify potential benefits and barriers associated with using an e-form to capture PROMs; and (c) gather feedback on user experience.

Methods
Participants completed both a paper and an e-form of the questionnaires in a randomized order, following which they completed a feedback survey. Agreement of the scores between the forms were statistically analyzed using the intraclass correlation coefficient (ICC) (95 % Confidence Interval (CI)) and bias was assessed using a Bland-Altman plot. Completion and processing times of the forms were compared using mean and median measures. Quantitative analysis was performed to assess user experience ratings, while comments were qualitatively analyzed to identify important themes.

Results
196 patients participated in this project. Scores on the forms had high ICC agreement > 0.9. New patients took longer than returning patients to complete the forms. Overall, the e-form was completed and processed in a shorter amount of time than the paper form. 83 % of survey respondents indicated that they either preferred the e-form or had no preference. Approximately 10 % of respondents suggested improvements to improve the user interface.

Conclusions
E-forms collect comparable information in an efficient manner to paper forms. Given that patients and caregivers indicated they preferred completing PROMs in this manner, we will implement their suggested changes and incorporate e-forms as standard practice for PROMs collection in our pediatric rheumatology clinic.
Myoelectric prosthesis users and non-disabled individuals wearing a simulated prosthesis exhibit similar compensatory movement strategies
Authors: Williams Heather E. , Chapman Craig S. , Pilarski Patrick M. , Vette Albert H. , Hebert Jacqueline S. 
Published: May 2021

Abstract
Background
Research studies on upper limb prosthesis function often rely on the use of simulated myoelectric prostheses (attached to and operated by individuals with intact limbs), primarily to increase participant sample size. However, it is not known if these devices elicit the same movement strategies as myoelectric prostheses (operated by individuals with amputation). The objective of this study was to address the question of whether non-disabled individuals using simulated prostheses employ the same compensatory movements (measured by hand and upper body kinematics) as individuals who use actual myoelectric prostheses.

Methods
The upper limb movements of two participant groups were investigated: (1) twelve non-disabled individuals wearing a simulated prosthesis, and (2) three individuals with transradial amputation using their custom-fitted myoelectric devices. Motion capture was used for data collection while participants performed a standardized functional task. Performance metrics, hand movements, and upper body angular kinematics were calculated. For each participant group, these measures were compared to those from a normative baseline dataset. Each deviation from normative movement behaviour, by either participant group, indicated that compensatory movements were used during task performance.

Results
Results show that participants using either a simulated or actual myoelectric prosthesis exhibited similar deviations from normative behaviour in phase durations, hand velocities, hand trajectories, number of movement units, grip aperture plateaus, and trunk and shoulder ranges of motion.

Conclusions
This study suggests that the use of a simulated prosthetic device in upper limb research offers a reasonable approximation of compensatory movements employed by a low- to moderately-skilled transradial myoelectric prosthesis user.
Broad respiratory testing to identify SARS-CoV-2 viral co-circulation and inform diagnostic stewardship in the COVID-19 pandemic
Authors: Marshall Natalie C. , Kariyawasam Ruwandi M. , Zelyas Nathan , Kanji Jamil N. , Diggle Mathew A. 
Published: May 2021

Abstract
Background
SARS-CoV-2 infection can present with a broad clinical differential that includes many other respiratory viruses; therefore, accurate tests are crucial to distinguish true COVID-19 cases from pathogens that do not require urgent public health interventions. Co-circulation of other respiratory viruses is largely unknown during the COVID-19 pandemic but would inform strategies to rapidly and accurately test patients with respiratory symptoms.

Methods
This study retrospectively examined 298,415 respiratory specimens collected from symptomatic patients for SARS-CoV-2 testing in the three months since COVID-19 was initially documented in the province of Alberta, Canada (March-May, 2020). By focusing on 52,285 specimens that were also tested with the Luminex Respiratory Pathogen Panel for 17 other pathogens, this study examines the prevalence of 18 potentially co-circulating pathogens and their relative rates in prior years versus since COVID-19 emerged, including four endemic coronaviruses.

Results
SARS-CoV-2 was identified in 2.2% of all specimens. Parallel broad multiplex testing detected additional pathogens in only 3.4% of these SARS-CoV-2-positive specimens: significantly less than in SARS-CoV-2-negative specimens (p < 0.0001), suggesting very low rates of SARS-CoV-2 co-infection. Furthermore, the overall co-infection rate was significantly lower among specimens with SARS-CoV-2 detected (p < 0.0001). Finally, less than 0.005% of all specimens tested positive for both SARS-CoV-2 and any of the four endemic coronaviruses tested, strongly suggesting neither co-infection nor cross-reactivity between these coronaviruses.

Conclusions
Broad respiratory pathogen testing rarely detected additional pathogens in SARS-CoV-2-positive specimens. While helpful to understand co-circulation of respiratory viruses causing similar symptoms as COVID-19, ultimately these broad tests were resource-intensive and inflexible in a time when clinical laboratories face unprecedented demand for respiratory virus testing, with further increases expected during influenza season. A transition from broad, multiplex tests toward streamlined diagnostic algorithms targeting respiratory pathogens of public health concern could simultaneously reduce the overall burden on clinical laboratories while prioritizing testing of pathogens of public health importance. This is particularly valuable with ongoing strains on testing resources, exacerbated during influenza seasons.
Giant vascular eccrine spiradenoma: the first case in the scrotum and review of the literature author
Authors: Li Zan , Li Gang , Jiang Xin , Fu Xiaoming 
Published: May 2021

AbstractBackgroundGiant vascular eccrine spiradenoma is a rare variant of eccrine spiradenoma. It is different from the eccrine spiradenoma in its larger size and greater degree of vascularity. It is often clinically confusedwith a vascular or malignant tumor.Case presentationHere, we report a case of a 67-year-old man who presented with a tumor in the scrotum scrotal region for 6 years. The tumor had begun as a small nodule and had grown slowly with over time. Surgical excision and pathological examination revealed that the lesion was the a giant vascular eccrine spiradenoma.ConclusionThis study reports the first case of giant vascular eccrine spiradenoma in the scrotum.
Danon disease: a case report and literature review
Authors: Xu Jiamin , Li Zhu , Liu Yihai , Zhang Xinlin , Niu Fengnan , Zheng Hongyan , Wang Lian , Kang Lina , Wang Kun , Xu Biao 
Published: May 2021

AbstractBackgroundDanon disease (DD) is a rare x-linked dominant multisystemic disorder with a clinical triad of severe cardiomyopathy, skeletal myopathy, and mental retardation. It is caused by a defect in the lysosomal-associated membrane protein-2 (LAMP2) gene, which leads to the formation of autophagic vacuoles containing glycogen granule deposits in skeletal and cardiac muscle fibers. So far, more than 50 different mutations inLAMP2 have been identified.Case presentationHere, we report an 18-year-old male patient who was hospitalized for heart failure. Biopsy of the left lateral femoral muscle revealed scattered autophagic vacuoles in the muscle fibers with increased glycogen. Next generation sequencing (NGS) was used to detect gene mutations of the proband sample and a novel frameshift mutation (c.1052delG) has been identified in exon 8 ofLAMP2, which leads to truncation of the protein.ConclusionWe found a novel frameshift mutation, a hemizygous mutation (c.1052delG) in exon 8 ofLAMP2, identified as presenting the hypertrophic cardiomyopathy (HCM) phenotype. Genetic analysis is the gold standard for the diagnosis of DD and is essential to determine appropriate treatment strategies and to confirm the genetic risk of family members.
Qualitative assessment of patients’ perspectives and needs from community pharmacists in substance use disorder management
Authors: Fatani Sarah , Bakke Daniel , D’Eon Marcel , El-Aneed Anas 
Published: May 2021

Abstract
Background
Non-medical use of psychoactive substances is a common harmful behavior that leads to the development of Substance Use Disorders (SUDs). SUD is a significant health concern that causes adverse health consequences and elevates the economic burden on the health care system. SUD treatment plans that utilize a patient-centered approach have demonstrated improved treatment outcomes. It is essential for health care providers, including community pharmacists, to understand patients’ needs and prioritize them. Therefore, this study was conducted to explore the perspective of patients living with SUDs or who used substances non-medically regarding community pharmacist services and the delivery of services in a community pharmacy setting. The study took place in Saskatoon, a small urban center of Saskatchewan, Canada.

Methods
Qualitative methodology was used for this research inquiry. Four focus groups were conducted, with a total of 20 individuals who had experienced substance use and accessed community pharmacy services. The discussion of the four focus groups was transcribed verbatim and analyzed independently by two researchers. Agreement on the emergent themes was reached through discussion between the two researchers.

Results
Data analysis resulted in four themes that described participants’ perspectives about community pharmacists. The four emergent themes are: 1) conflicted experiences with community pharmacists, 2) lack of knowledge concerning community pharmacists’ extended services, 3) negative experiences in Opioid Agonist Therapy (OAT) program, and 4) needs from community pharmacists.

Conclusion
There is significant potential for the patient-pharmacist relationship to address the varying needs of patients who use substances and improve their overall health care experience. Patients who use substances are receptive to pharmacists’ services beyond dispensary; however, respectful communication, provision of drug-related information, and counseling are among the primary demands. Future research should focus on studying the impact of meeting the needs of patients on their treatment outcomes.