bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent Heart Attacks in a Young Lady
Authors: Ekladious Adel
Published: August 2022

24-year-old woman presented to our hospital with chest pain, new ECG changes and high troponin suggestive of non-ST Myocardial infarction, patient gave history of another two heart attacks at the age of 20 and 21, on both occasions, she was treated with angioplasty and no stenting. Her past medical history was significant for recurrent meniscal tear on both knees which was treated conservative, when patient was 15-year-old, she was diagnosed as carotid–cavernous fistula and Treated with endovascular therapy, her family history was noted for her sister having small bowel rupture at the age of 18 year, her brother had two strokes at the age of 18 and 19, patient also was known to have recurrent dislocation of right shoulder and delayed wound healing. Examination showed scattered bruising, blue sclera, hyperelasticty of skin over elbow joints, MRA of whole body showed aneurysm of both internal iliac vessels, coronary CT showed aneurysm in the left anterior descending and right coronary arteries, differential diagnosis was discussed with the patient who gave a consent for genetic study which came positive for COL3A1 and confirmed the diagnosis of Vascular Ehlers Donals Syndrome (formally called Ehlers Donals Syndrome type 4). Patient agreed for genetic counselling, and first-degree family agreed for genetic testing, in the article we will report the case and discuss the differential diagnosis.
Venous and Arterial Thoracic Outlet Syndrome Requiring Surgical Intervention: Two Case Reports
Authors: Mahmoudzadeh Samaan , Parrill Allison , Shaikh Dooniya , McGhee Kathryn , Lev Steven , Ramanathan Anantha
Published: August 2022

Background: Thoracic outlet syndrome represents a spectrum of diseases depending on the structures involved. Most cases of thoracic outlet syndrome (TOS) are neurogenic while arterial and venous TOS constitute only 5% of the cases. Paget-Schroetter syndrome represents an acute complication of venous thoracic outlet syndrome (vTOS) commonly occurring in physically active individuals participating in strenuous upper body exercises. Arterial thoracic outlet syndrome (aTOS) is usually associated with bony abnormalities. We discuss one patient of each type who presented with acute thrombosis to illustrate the different associated factors and treatment options. Case Report(s): An 18-year-old Hispanic male presented with six days of left upper extremity (LUE) edema and pain that began following an upper body exercise. He was treated by pharmacomechanical thrombectomy followed by ultrasound assisted catheter-directed thrombolysis. Subsequently the patient underwent trans axillary surgical decompression of the thoracic outlet. A 59-year-old South Asian woman presented with worsening LUE pain, weakness and paresthesia of 10 days duration. She underwent pharmacomechanical thrombectomy with angioplasty followed by supraclavicular thoracic outlet decompression. Conclusions: Treatment of TOS presenting with thrombosis should consist of prompt thrombectomy followed by surgical decompression.
BYOD, the Advancement of Enterprise and Mobile Civilization: Challenges and Prevalence
Authors: Abdulkarim Sadiq , Muhammed Abubakar Ismail , Ahmad Samaila Kasimu , Ibrahim Muhammed
Published: August 2022

The industries keep expanding its horizon, modern computing on the forefront of the labor market and its industrial reformations. As these modern computing backbones extends, hence the need for more subordinating devices. This paved the way and allow for the resounding evolution of the modern computing as against the stone-aged and analogues era. As the world keeps up its nocturnal submersions, so also the need for a corresponding drift in the directions of mobile computing. The trends and evolution of mobile computers such as smartphones and laptops has bring about a swift turnaround in the fields of computing. Users are able to move freely with their devices and use it extensively to utmost satisfactions. Mobile computers play vital and essential roles in our lives. Users use these devices almost everywhere they are allowed such as homes, workout hubs, beaches, tourist grounds, workplace etc. Daily usage of these devices tends to create some sorts of mutual relationships between the users and the devices. These relationships range from comfortability, familiarity, ease-of-use etc. As these devices tend to assume an appreciable fraction of our life's endeavors affecting our lives in diverse ways, it tends to find its way in almost all aspects of our lives. These essences brings about a new trend where employees are allowed to bring their own devices and use it in all aspect of their work deliverables. The concept that describes this trend is known as "Bring your own device" BYOD.
Oral feeding skills in premature infants: A concept analysis
Authors: Astuti Dyah Dwi , Rustina Yeni , Wanda Dessie
Published: August 2022

Background:  The delay in developing oral feeding skills becomes a problem experienced by premature infants. One of the reasons for the delay may be related to inconsistent definitions of oral feeding skills, which can cause discrepancies in the provision of nursing care.
Objective: This study aimed to clarify the concept of oral feeding skills in premature infants.
Methods: The Walker and Avant concept analysis method was used. A literature search was also conducted from five databases: CINAHL, PubMed, ProQuest, EMBASE, and Google Scholar, to find articles between January 2020 and December 2022.
Results: The literature search obtained 20 articles on oral feeding skills from various disciplines. Five attributes were developed from the concept analysis, including (1) coordination ability to suck, swallow, and breathe, (2) the ability to regulate oral-motor functions, (3) the ability to regulate sensory functions, (4) the ability to maintain the stability of physiology function, and (5) the ability to regulate feeding behavior. Antecedents to oral feeding skills include immaturity of the nervous system, gestational age, feeding intolerance, increased length of stay and cost of care, increased rehospitalization, stress on parents, and increased morbidity and mortality. Consequences include optimization of growth and development, reduction of length of stay and cost of hospitalization, increased bonding attachment, increased self-efficacy of parents in caring for premature infants, and improvement of the quality of life of premature infants.
Conclusion: The concept analysis provides five comprehensive attributes and their antecedents and consequences. However, this concept can be used to provide nursing care to premature infants, assess the criteria for discharge, and optimize nutrition for the growth and development of premature infants.
Translation, adaptation, and validation of the Filipino version of the Caring Behaviors Inventory
Authors: Tamayo Reiner Lorenzo , Tating Dan Louie Renz , Gilo Ericka Louise , Mugol Hannah Kristine , Laureta Karen Grace
Published: August 2022

Background: The way patients perceive nurses’ caring behaviors can potentially impact patient outcomes and satisfaction. Studies have revealed incongruence between nurses’ and patients’ perceptions with regard to which behaviors are considered caring.
Objective: This study aimed to conduct a cross-cultural validation and evaluation of the psychometric properties of the Caring Behaviors Inventory (CBI-16), a self-report questionnaire, from English to Filipino.
Methods: A descriptive cross-sectional design involving forward and back-translation with bilingual translators, expert validation, and a survey in a sample of patients and nurses was used. The psychometric evaluation used a sample of 142 staff nurses and 180 hospitalized patients. Exploratory factor analysis, internal consistency reliability, and inferential statistics were used for data analysis.
Results: The Filipino version of the CBI-16 (CBI-16-FIL) had excellent internal consistency (Cronbach’s alpha of 0.95) and a unidimensional factor structure (accounted for 85% of total variance). The CBI-16-FIL was found to be a valid, reliable, and unidimensional tool to measure the perceptions of nurse caring behaviors in the Philippines.
Conclusion: The CBI-16-FIL can be used to measure perceptions of nurse caring behaviors. There is a need for further studies involving other cultures, dyadic samples of nurses and patients, and larger sample sizes.
Online ‘chatting’ interviews: An acceptable method for qualitative data collection
Authors: Gunawan Joko , Marzilli Colleen , Aungsuroch Yupin
Published: August 2022

Qualitative research methods allow researchers to understand the experiences of patients, nurses, and other healthcare professionals. Qualitative research also provides scientists with information about how decisions are made and the aspects of existing interventions. However, to get to obtain this important information, qualitative research requires holistic, rich, and nuanced data that can be analyzed to determine themes, categories, or emerging patterns. Generally, offline or in-person interviews, focus group discussions, and observations are three core approaches to data collection. However, geographical barriers, logistic challenges, and emergency conditions, such as the COVID-19 pandemic have necessitated the utilization of online interviews, including chatting as an alternative way of collecting data. This editorial aims to discuss the possibility of online chat interviews as an acceptable design in qualitative data collection.
An Analysis of the Crisis by Exploring the Wild Geese Families, a Portrait of Modern People
Authors:   The Korean Society of Culture and Convergence, Choi Sookyong , Lee Hyunsim
Published: August 2022

This study attempted to explore the effects of family separation on the process of maintaining wild geese family relationships through the movie 'Single Rider'. This study collected significant data from the wild goose family in the film, such as their dialogue, nonverbal components, and major daily lives or events that cause behavioral changes. This data changed to texts were analyzed with a Matrix analysis by applying A Crisis Model of the Wild Geese Family Relationship. The results of analysis were these. Firstly, the lack or absence of intimacy, sex life, and trust between wild goose couples has had a dangerous effect on their relationship. Secondly, the loss of role due to the fathers’ absence brought a crisis to the relationship between fathers and children. Finally, from the perspective of each of the couples, wild goose fathers spend a long time living alone, which causes problems and reduces their health-related quality of life, and wild goose mothers also experienced identity confusion and crisis due to role changes caused by living separately. These results show that due to the instability of family separation itself, these wild geese families eventually raised possibilities of family disruptions or break-up's.
A Study on the Creation of Meanings of the Auxiliary Verb ‘see’ and ‘throw away’ in Lee sang’s Poetry
Authors:   The Korean Society of Culture and Convergence, Cho Haeok
Published: August 2022

In this paper, using Lee sang’s Korean poetry as the text, the characteristics of auxiliary verbs appearing in poetry were examined, and the relationship between auxiliary verbs and the formation of Lee sang’s poetry was examined. In Lee sang’s Korean poetry works, ‘see’ is reflected in the speaker’s feelings of alienation and the speaker’s desire to keep a psychological distance from the situation they are facing. ‘See’ plays a role in strengthening the psychology of separating oneself from the situation the speaker is facing and trying to keep a distance. ‘Throw away’ is the auxiliary verb with the second highest frequency of appearance in Lee sang’s poetry. The auxiliary verb ‘throw away’ is the meaning of inconvenience, and the meaning of relief. The auxiliary verb ‘throw away’ that creates the meaning of inconvenience reveals the time of irreversibility. In the negative context of the auxiliary verb ‘throw away’, the speaker’s feelings of solitude are denied or blocked. The third case is when ‘throw away’ is used as a double auxiliary verb composed of ‘throw away’ + ‘want’, the meaning of relief is not realized.
A Study on Korean Culture Education Using Intertextual Picture Book Approach
Authors:   The Korean Society of Culture and Convergence, Kim Jiyoung , Choi Eunkyung
Published: August 2022

The purpose of this study was to propose an educational plan using an intertextual picture book approach under the theme of 'family', one of the contents of Korean cultural education. To this end, the study of Korean culture education was reviewed, and a model for Korean culture education was presented by combining a complementary text arrangement among the intertextuality approaches into a picture book. The picture book selected a Korean picture book containing the sensitivity of Korean culture, and the subjects of learning were Korean middle and high-level learners so that active interactions such as talking, discussion, and presentation could occur. It will find the diversity of Korean culture different from the learner's own culture through picture books, recognize, accept, and naturally organize their thoughts through interaction and discussion with learners. Through this study, it is expected to provide a new direction for Korean cultural education through picture books and to be used as a teaching method for Korean cultural education for foreign students in the future.
A Study on the College Selection Factors of Regional Universities: Focusing on Major Performance Indicators
Authors:   The Korean Society of Culture and Convergence, Kim Juseuk , Lee Jaejun
Published: August 2022

The purpose of this study is to investigate the college selection factors recognized by prospective freshmen in the college selection process, and to analyze the factors affecting them. Various data related to the educational performance of local four-year universities were collected. The results of the survey on university lecture evaluation, curriculum satisfaction, core competency diagnosis, freshman admission rate, enrollment rate, and employment rate were analyzed through correlation and regression analysis. Some factors showed a positive correlation among freshman recruitment rate, employment rate, core competency diagnosis, curriculum satisfaction, and lecture evaluation. In addition, as a result of regression analysis to determine how much the freshman recruitment rate was predicted, the employment rate was adopted. By analyzing these factors, it was found that increasing the employment rate is important for the survival of local universities.
Assessment of CO2 biofixation and bioenergy potential of microalga Gonium pectorale through its biomass pyrolysis, and elucidation of pyrolysis reaction via kinetics modeling and artificial neural network
Authors: Altriki Ahmed , Ali Imtiaz , Razzak Shaikh Abdur , Ahmad Irshad , Farooq Wasif
Published: August 2022

This study investigates CO2 biofixation and pyrolytic kinetics of microalga G. pectorale using model-fitting and model-free methods. Microalga was grown in two different media. The highest rate of CO2 fixation (0.130 g/L/day) was observed at a CO2 concentration of 2%. The pyrokinetics of the biomass was performed by a thermogravimetric analyzer (TGA). Thermogravimetric (TG) and derivative thermogravimetric (DTG) curves at 5, 10 and 20°C/min indicated the presence of multiple peaks in the active pyrolysis zones. The activation energy was calculated by different model-free methods such as Friedman, Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS), and Popescu. The obtained activation energy which are 61.7–287 kJ/mol using Friedman, 40.6–262 kJ/mol using FWO, 35–262 kJ/mol using KAS, and 66.4–255 kJ/mol using Popescu showed good agreement with the experimental values with higher than 0.96 determination coefficient (R2). Moreover, it was found that the most probable reaction mechanism for G. pectorale pyrolysis was a third-order function. Furthermore, the multilayer perceptron-based artificial neural network (MLP-ANN) regression model of the 4-10-1 architecture demonstrated excellent agreement with the experimental values of the thermal decomposition of the G. pectoral. Therefore, the study suggests that the MLP-ANN regression model could be utilized to predict thermogravimetric parameters.
Sequelae of Hospitalization for Diabetic Foot Ulcers at LASUTH Ikeja Lagos: A Prospective Observational Study
Authors: Adeleye Olufunmilayo Olubusola , Williams Adetutu Oluwatosin , Dada Akin Olusola , Ugwu Ejiofor T. , Ogbera Anthonia Okeoghene , Sodipo Olujimi Olanrewaju
Published: August 2022

Diabetic foot ulcers (DFUs) remain important sequelae of diabetes (DM) which cause debilitating effects on the sufferer. The evolution of some aspects of epidemiology and the current clinical impact of DFUs was examined.

Methods

A single-center prospective observational study. Study subjects were consecutively recruited.

Results

Total medical admissions during the study period were 2288, 350 were DM related, out of these 112 were admitted for DFU. 32% of total DM admissions were for DFU. The mean age of the study subjects is 58 ± 11.0 range is from 35 years to 87 years. Males were slightly predominant (51.8%). Most of them were actively employed (92%), and the majority were in the 55 to 64 years age category. Most of them had not been diabetic for longer than 8 years (61%). The mean duration of DM is 8.32±7.27 years. The mean duration of ulcer at presentation was 72.0±138.13 days. The majority of the patients (80.3%) presented with severe (grades 3 to 5) ulcers, Wagner grade four was the most predominant. Regarding clinical outcome, 24 (24.7%) had an amputation, 3 of which were minor. The factor that was associated with amputation was concomitant heart failure – OR 6.00 CI 0.589-61.07, 0.498-4.856. Death occurred in 16 (18.4%). The factors associated with mortality were severe anemia OR 2.00 CI 0.65 – 6.113, severe renal impairment requiring dialysis OR 3.93 CI 0.232-66.5, concomitant stroke OR 8.42 CI 0.71-99.6, and peripheral arterial disease- OR 18.33 CI 2.27 -147 p-value- 0.006.

Conclusion

The hallmark of DFU in this report is late presentation, it accounted for a significant proportion of the total medical admissions, although the case fatality of DFU reduced from previous reports from the center, mortality, and amputation rates are still unacceptably high. Concomittant heart failure was a factor of amputation. Mortality was associated with severe anemia, renal impairment and peripheral arterial disease.
A droplet-based microfluidic approach to isolating functional bacteria from gut microbiota
Authors: Yin Jianan , Chen Xiuzhao , Li Xiaobo , Kang Guangbo , Wang Ping , Song Yanqing , Ijaz Umer Zeeshan , Yin Huabing , Huang He
Published: August 2022

Metabolic interactions within gut microbiota play a vital role in human health and disease. Targeting metabolically interacting bacteria could provide effective treatments; however, obtaining functional bacteria remains a significant challenge due to the complexity of gut microbiota. Here, we developed a facile droplet-based approach to isolate and enrich functional gut bacteria that could utilize metabolites from an engineered butyrate-producing bacteria (EBPB) of anti-obesity potential. This involves the high throughput formation of single-bacteria droplets, followed by culturing “droplets” on agar plates to form discrete single-cell colonies. This approach eliminates the need for sophisticated s instruments to sort droplets and thus allows the operation hosted in a traditional anaerobic chamber. In comparison to the traditional culture, the droplet-based approach obtained a community of substantially higher diversity and evenness. Using the conditioned plates containing metabolites from the EBPB supernatant, we obtained gut bacteria closely associated or interacting with the EBPB. These include anaerobic Lactobacillus and Bifidobacterium, which are often used as probiotics. The study illustrates the potential of our approach in the search for the associated bacteria within the gut microbiota and retrieving those yet-to-be cultured.
Relationship between Helicobacter pylori infection and gastrointestinal microecology
Authors: Xu Wenting , Xu Liming , Xu Chengfu
Published: August 2022

The prevalence of Helicobacter pylori (H. pylori) infection has exceeded 50% worldwide, and it is considered a high-risk factor for chronic gastritis, peptic ulcer, gastric adenocarcinoma, gastroesophageal reflux disease and functional dyspepsia. H. pylori drug resistance is a common problem worldwide. In recent years, the relationship between H. pylori infection and gastrointestinal microecology has received much attention. H. pylori infection changes the structure and composition of gastrointestinal microflora by regulating the gastrointestinal microecological environment, local pH value, cytokines and antimicrobial peptides, and immune response and then plays a crucial role in the occurrence and development of digestive system tumors, liver metabolism and extragastrointestinal diseases. The quadruple strategy of H. pylori eradication can also aggravate gastrointestinal microflora disorder. However, probiotics can reduce intestinal flora changes and imbalances through different mechanisms, thus enhancing the efficacy of H. pylori eradication therapy and reducing adverse reactions caused by eradication therapy. Therefore, this paper reviews the relationship between H. pylori infection and gastrointestinal microecology and its clinical application, providing a basis for clinical treatment.
Development of a panel of three multiplex allele-specific qRT-PCR assays for quick differentiation of recombinant variants and Omicron subvariants of SARS-CoV-2
Authors: Li Jianguo , Gao Zefeng , Chen Jing , Cheng Ruiling , Niu Jiahui , Zhang Jialei , Yang You , Yuan Ximei , Xia Juan , Mao Guoli , Liu Hulong , Dong Yongkang , Wu Changxin
Published: August 2022

Quick differentiation of the circulating variants and the emerging recombinant variants of SARS-CoV-2 is essential to monitor their transmission. However, the widely used gene sequencing method is time-consuming and costly when facing the viral recombinant variants, because partial or whole genome sequencing is required. Allele-specific real time RT-PCR (qRT-PCR) represents a quick and cost-effective method in SNP genotyping and has been successfully applied for SARS-CoV-2 variant screening. In the present study, we developed a panel of 3 multiplex allele-specific qRT-PCR assays targeting 12 key differential mutations for quick differentiation of SARS-CoV-2 recombinant variants (XD and XE) and Omicron subvariants (BA.1 and BA.2). Two parallel multiplex qRT-PCR reactions were designed to separately target the protype allele and the mutated allele of the four mutations in each allele-specific qRT-PCR assay. The variation of Cp values (ΔCp) between the two multiplex qRT-PCR reactions was applied for mutation determination. The developed multiplex allele-specific qRT-PCR assays exhibited outstanding analytical sensitivities (with limits of detection [LoDs] of 2.97-27.43 copies per reaction), wide linear detection ranges (107-100 copies per reaction), good amplification efficiencies (82% to 95%), good reproducibility (Coefficient of Variations (CVs) < 5% in both intra-assay and inter-assay tests) and clinical performances (99.5%-100% consistency with Sanger sequencing). The developed multiplex allele-specific qRT-PCR assays in this study provide an alternative tool for quick differentiation of SARS-CoV-2 recombinant variants (XD and XE) and Omicron subvariants (BA.1 and BA.2).
Cascading impacts of a climate-driven ecosystem transition intensifies population vulnerabilities and fishery collapse
Authors: Rogers-Bennett Laura , Catton Cynthia A.
Published: August 2022

The recent large-scale intensification of marine heatwaves, and other climate-related stressors, has dramatically impacted biogenic habitats around the globe, including marine ecosystems such as coral reefs, seagrasses, and kelp forests. While the impacts to foundation species may be of particular concern, these ecological catastrophes underscore the need to examine how whole systems respond to a suite of stressors. The recent climate-driven collapse of the bull kelp forest and recreational red abalone fishery in northern California provides an example of unanticipated ripple and lagged effects in the system, intensifying vulnerabilities and accelerating population and fishery collapse. For this case study, we examined 15 years (2003–2018) of biological survey data on the bull kelp forest ecosystem—before, during, and after an extreme climate event. We document the interactions and complexity of impacts over time, as well as the resulting increased vulnerability of red abalone to additional anthropogenic, biological, and environmental stressors. We observed progressively stronger population-level responses of the red abalone to the marine heatwave and the regional loss of kelp, driving the movement of adults and juveniles in search of food. As food remained scarce, we documented the loss of productivity with diminished gonad and body condition, the absence of larval or newly-settled abalone, mass mortalities, and shoreward shifts in depth distributions. With 40% of the population dead or dying, juvenile and trophy-sized abalone abandoning cryptic habitats, the shift in the distribution to shallower depths increased the vulnerability of red abalone to the fishery. Other anthropogenic, biological, and climate-related stressors that disproportionately impact shallow habitats are now a growing concern for the survivors. For red abalone, previously unanticipated cascading risks include increased wave energy, warming air temperatures, freshwater flooding, landslides, as well as possible oil spills and harmful algal blooms. Climate-driven changes in vulnerability to fishing and environmental stressors present significant challenges for sustainable natural resource management in dynamic stressed systems, and underscore the need for continued system-focused monitoring. We present a conceptual framework supporting similar ecosystem investigations of recent and future climate impacts to inform adaptive ecosystem-based management strategies.
Non-coding RNAs to regulate cardiomyocyte proliferation: A new trend in therapeutic cardiac regeneration
Authors: Qin Kele , Xie Xiaohui , Tang Weijie , Yang Danni , Peng Jun , Guo Jianjun , Yang Jinfu , Fan Chengming
Published: August 2022

Cardiovascular diseases remain the leading cause of death worldwide, particularly ischemic heart disease (IHD). It is also classified as incurable given the irreversible damage it causes to cardiomyocytes. Thus, myocardial tissue rejuvenation following ischemia is one of the global primary research concerns for scientists. Interestingly, the mammalian heart thrives after an injury during the embryonic or neonatal period; however, this ability disappears with increasing age. Previous studies have found that specific non-coding (nc) RNAs play a pivotal role in this process. Hence, the review herein summarizes the research on cardiomyocyte regenerative medicine in recent years and sets forth the biological functions and mechanisms of the micro (mi)RNA, long non-coding (lnc)RNA, and circular (circ)RNA in the posttranscriptional regulation of cardiomyocytes. In addition, this review summarizes the roles of ncRNAs in specific species while enumerating potential therapeutic strategies for myocardial infarction.
Appropriate controls for digital therapeutic clinical trials: A narrative review of control conditions in clinical trials of digital therapeutics (DTx) deploying psychosocial, cognitive, or behavioral content
Authors: Lutz Jacqueline , Offidani Emanuela , Taraboanta Laura , Lakhan Shaheen E. , Campellone Timothy R.
Published: August 2022

Digital therapeutics (DTx) are software programs that treat a disease or condition. Increasingly, DTx are part of medical care, and in the US healthcare system they are regulated by the FDA as Software as a Medical Device (SaMD). Randomized controlled trials (RCT) remain a key evidence generation step for most DTx. However, developing a unified approach to the design of appropriate control conditions has been a challenge for two main reasons: (1) inheriting control condition definitions from pharmacotherapy and medical device RCT that may not directly apply, and (2) challenges in establishing control conditions for psychosocial interventions that build the core of many DTx. In our critical review we summarize different approaches to control conditions and patient blinding in RCT evaluating DTx with psychosocial, cognitive or behavioral content. We identify control condition choices, ranging from very minimal digital controls to more complex and stringent digital applications that contain aspects of “fake” therapy, general wellness content or games. Our review of RCTs reveals room for improvement in describing and naming control conditions more consistently. We further discuss challenges in defining placebo controls for DTx and ways in which control choices may have a therapeutic effect. While no one-size-fits-all control conditions and study designs will apply to all DTx, we propose points to consider for defining appropriate digital control conditions. At the same time, given the rapid iterative development and optimization of DTx, treatments with low risk profile may be evaluated with minimal digital controls followed by extensive real-world effectiveness trials.
Timing errors and temporal uncertainty in clinical databases—A narrative review
Authors: Goodwin Andrew J. , Eytan Danny , Dixon William , Goodfellow Sebastian D. , Doherty Zakary , Greer Robert W. , McEwan Alistair , Tracy Mark , Laussen Peter C. , Assadi Azadeh , Mazwi Mjaye
Published: August 2022

A firm concept of time is essential for establishing causality in a clinical setting. Review of critical incidents and generation of study hypotheses require a robust understanding of the sequence of events but conducting such work can be problematic when timestamps are recorded by independent and unsynchronized clocks. Most clinical models implicitly assume that timestamps have been measured accurately and precisely, but this custom will need to be re-evaluated if our algorithms and models are to make meaningful use of higher frequency physiological data sources. In this narrative review we explore factors that can result in timestamps being erroneously recorded in a clinical setting, with particular focus on systems that may be present in a critical care unit. We discuss how clocks, medical devices, data storage systems, algorithmic effects, human factors, and other external systems may affect the accuracy and precision of recorded timestamps. The concept of temporal uncertainty is introduced, and a holistic approach to timing accuracy, precision, and uncertainty is proposed. This quantitative approach to modeling temporal uncertainty provides a basis to achieve enhanced model generalizability and improved analytical outcomes.
Inside the Noonan “universe”: Literature review on growth, GH/IGF axis and rhGH treatment: Facts and concerns
Authors: Stagi Stefano , Ferrari Vittorio , Ferrari Marta , Priolo Manuela , Tartaglia Marco
Published: August 2022

Noonan syndrome (NS) is a disorder characterized by a typical facial gestalt, congenital heart defects, variable cognitive deficits, skeletal defects, and short stature. NS is caused by germline pathogenic variants in genes coding proteins with a role in the RAS/mitogen-activated protein kinase signaling pathway, and it is typically associated with substantial genetic and clinical complexity and variability. Short stature is a cardinal feature in NS, with evidence indicating that growth hormone (GH) deficiency, partial GH insensitivity, and altered response to insulin-like growth factor I (IGF-1) are contributing events for growth failure in these patients. Decreased IGF-I, together with low/normal responses to GH pharmacological provocation tests, indicating a variable presence of GH deficiency/resistance, in particular in subjects with pathogenic PTPN11 variants, are frequently reported. Nonetheless, short- and long-term studies have demonstrated a consistent and significant increase in height velocity (HV) in NS children and adolescents treated with recombinant human GH (rhGH). While the overall experience with rhGH treatment in NS patients with short stature is reassuring, it is difficult to systematically compare published data due to heterogeneous protocols, potential enrolment bias, the small size of cohorts in many studies, different cohort selection criteria and varying durations of therapy. Furthermore, in most studies, the genetic information is lacking. NS is associated with a higher risk of benign and malignant proliferative disorders and hypertrophic cardiomyopathy, and rhGH treatment may further increase risk in these patients, especially as dosages vary widely. Herein we provide an updated review of aspects related to growth, altered function of the GH/IGF axis and cell response to GH/IGF stimulation, rhGH treatment and its possible adverse events. Given the clinical variability and genetic heterogeneity of NS, treatment with rhGH should be personalized and a conservative approach with judicious surveillance is recommended. Depending on the genotype, an individualized follow-up and close monitoring during rhGH treatments, also focusing on screening for neoplasms, should be considered.
Serum lipidomics profiles reveal potential lipid markers for prediabetes and type 2 diabetes in patients from multiple communities
Authors: Xuan Qiuhui , Hu Chunxiu , Zhang Yinan , Wang Qingqing , Zhao Xinjie , Liu Xinyu , Wang Congrong , Jia Weiping , Xu Guowang
Published: August 2022

Objective

Dyslipidemia is a hallmark of diabetes mellitus (DM). However, specific lipid molecules closely associated with the initiation and progression of diabetes remain unclear. We used a pseudotargeted lipidomics approach to evaluate the complex lipid changes that occurred long before the diagnosis of type 2 diabetes mellitus (T2DM) and to identify novel lipid markers for screening prediabetes mellitus (PreDM) and T2DM in patients from multiple communities.

Methods

Four hundred and eighty-one subjects consisting of T2DM, three subtypes of PreDM, and normal controls (NC) were enrolled as discovery cohort. Serum lipidomic profiles of 481 subjects were analyzed using an ultrahigh performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS)-based pseudotargeted lipidomics method. The differential lipid molecules were further validated in an independent case-control study consisting of 150 PreDM, 234 T2DM and 94 NC.

Results

Multivariate discriminative analyses show that lipidomics data have considerable potential for identifying lipidome differences among T2DM, subtypes of PreDM and NC. Statistical associations of lipid (sub)species display significant variations in 11 lipid (sub)species levels for T2DM and distinctive differences in 8 lipid (sub)species levels between prediabetic and normoglycemic individuals, with further differences in 8 lipid (sub)species levels among subtypes of PreDM. Adjusted for sex, age and BMI, only two lipid (sub)species of fatty acid (FA) and phosphatidylcholine (PC) were associated at p< 0.05 for PreDM (all) and subtypes of PreDM. The defined lipid markers not only significantly improve the diagnostic accuracy of PreDM and T2DM but also effectively evaluating the risk of developing into each subtype of PreDM and T2DM when addition of age, sex, BMI, and FPG, respectively.

Conclusions

Our findings improve insights into the lipid metabolic complexity and interindividual variations among subtypes of PreDM and T2DM, beyond the well-known differences in dyslipidemia in clinic.
Cortisol values during the standard-dose cosyntropin stimulation test: Personal experience with Elecsys cortisol II assay
Authors: Husni Hasan , Abusamaan Mohammed S. , Dinparastisaleh Roshan , Sokoll Lori , Salvatori Roberto , Hamrahian Amir H.
Published: August 2022

Purpose

There has been debate regarding the appropriate cortisol cutoff during the cosyntropin stimulation test (CST) when newer cortisol assays are used. We aimed to evaluate the proper cortisol values during the standard dose CST in patients with normal hypothalamic-pituitary-adrenal (HPA) axis when the Elecsys® Cortisol II assay from Roche Diagnostics is used.

Methods

We retrospectively reviewed the medical records of patients evaluated for possible adrenal insufficiency using the standard-dose (250 mcg) CST from January 2018 to December 2020 and eventually judged to have a normal HPA axis. All the CSTs were done in the outpatient setting. Evaluation by an endocrinologist, restrictive exclusion criteria including prior glucocorticoid and opioid use, and lack of glucocorticoid treatment for at least 6 months after the CST was used to define normal HPA axis. The results are reported in the median (range).

Results

We identified 63 patients who met the inclusion criteria and were considered to have a normal HPA axis. The median age was 54.7 (27.6-89.1) years; 32 (51%) were female, and 27 (43%) were white. The duration of follow-up after the CST without any glucocorticoid replacement was 13.9 (6.3-43.9) months. Cortisol levels were 21.7 (15.7-29.1) µg/dl and 24.4 (17.9-35.8) µg/dl at 30- and 60-minutes after cosyntropin administration, respectively. The lowest cortisol levels at 30 and 60 minutes for patients with either normal TSH or gonadal axis (n=47) or in whom both axes were normal (n=18) were similar to the ones of the entire cohort.

Conclusion

Our study supports using a lower than previously recommended cortisol cutoff value at 30 minutes after Cosyntropin using the Roche Elecsys® Cortisol II assay. The lowest cortisol levels in our cohort were 15.7 and 17.9 µg/dL at 30 and 60 minutes after the CST, respectively. Therefore, it is essential to consider the time of cortisol draw after cosyntropin administration.
Genetic analysis of morphological traits in spring wheat from the Northeast of China by a genome-wide association study
Authors: Liu Wenlin , Li Yuyao , Sun Yan , Tang Jingquan , Che Jingyu , Yang Shuping , Wang Xiangyu , Zhang Rui , Zhang Hongji
Published: August 2022

Identification of the gene for agronomic traits is important for the wheat marker-assisted selection (MAS) breeding. To identify the new and stable loci for agronomic traits, including flag leaf length (FLL), flag leaf width (FLW), uppermost internode length (UIL), and plant morphology (PM, including prostrate, semi-prostrate, and erect). A total of 251 spring wheat accessions collected from the Northeast of China were used to conduct genome-wide association study (GWAS) by 55K SNP arrays. A total of 30 loci for morphological traits were detected, and each explained 4.8–17.9% of the phenotypic variations. Of these, 13 loci have been reported by previous studies, and the other 17 are novel. We have identified seven genes involved in the signal transduction, cell-cycle progression, and plant development pathway as candidate genes. This study provides new insights into the genetic basis of morphological traits. The associated SNPs and accessions with more of favorable alleles identified in this study could be used to promote the wheat breeding progresses.
Immunological signature of patients with thymic epithelial tumors and Good syndrome
Authors: Malfitano Anna Maria , D’Esposito Vittoria , De Placido Pietro , Tortora Marianna , Ottaviano Margaret , Pietroluongo Erica , Morra Rocco , Mucci Brigitta , Napolitano Fabiana , Montella Liliana , Giuliano Mario , De Placido Sabino , Terracciano Daniela , Palmieri Giovannella , Formisano Pietro
Published: August 2022

Background

Thymic epithelial tumors (TETs) are frequently accompanied by Good Syndrome (GS), a rare immunodeficiency, characterized by hypogammaglobulinemia and peripheral B cell lymphopenia. TETs can be also associated to other immunological disorders, both immunodeficiency and autoimmunity.

Methods

In this study, we enrolled TET patients with GS to address differences between patients with or without associated autoimmune diseases (AD). We analyzed the immunophenotype from peripheral blood of these patients focusing on selected immune cell subsets (CD4+T cells, CD8+T cells, T regulatory cells, NK cells, B-cells, monocytes, eosinophils, basophils, neutrophils) and serum levels of cytokines, chemokines and growth factors.

Results

We observed higher number of leucocytes, in particular lymphocytes, B lymphopenia and lower number of T regulatory cells in TET patients with associated AD compared to TET patients without AD. In the group of TET patients with AD, we also observed increased serum levels of IL-15, VEGF, IP-10, GM-CSF, IL-6, and MIP-1α. Thus, we identified considerable differences in the lymphocyte profiles of TET patients with and without ADs, in particular a reduction in the numbers of B lymphocytes and T-regulatory cells in the former, as well as differences in the serum levels of various immune modulators.

Conclusions

Although the pathogenic mechanisms are still unclear, our results add new knowledge to better understand the disease, suggesting the need of surveilling the immunophenotype of TET patients to ameliorate their clinical management.
Diagnostic and therapeutic dilemma in Stevens–Johnson syndrome-like acute graft-versus-host disease after liver transplantation: A case report
Authors: Hung Yi-Teng , Chang Yau-Ren , Wang Hsuan-Ning , Lee Wei-Chen , Lee Chen-Fang , Chen Chun-Bing
Published: August 2022

Background

Acute graft-versus-host disease (aGVHD) is a severe and fatal complication after orthotopic liver transplantation (OLT). Clinical manifestations of severe aGVHD can resemble drug-induced Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and there are also various medications, such as antibiotics and immunosuppressants, used after transplantation, causing a diagnostic dilemma. Furthermore, there have been no standardized diagnostic and therapeutic strategies for OLT-aGVHD due to its rarity.

Case summary

A 52-year-old man presented with generalized maculopapular eruptions, fever, and pancytopenia 1 month after OLT and 4 days after taking sulfamethoxazole/trimethoprim. After assessment of the scoring criteria for drug causality of drug allergy, histopathological findings of skin biopsy, lymphocyte activation test of the potential offending drug, and microchimerism study, the diagnosis was in favor of aGVHD mimicking SJS/TEN. Considering severe sepsis, the anti-tumor necrosis factor alpha (TNF-α) agent, etanercept, was used to replace tacrolimus and corticosteroid. Skin lesions resolved gradually after anti-TNF-α biologics rescue; tacrolimus and corticosteroid therapy were re-administrated after controlling sepsis. Pancytopenia recovered and the patient was discharged in a stable condition.

Conclusion

We demonstrated a diagnostic strategy for OLT-aGVHD. Targeting therapy with anti-TNF-α blockade and a temporary withdrawal of traditional immunosuppressants may be among effective and safe therapeutic options of OLT-aGVHD for those with severe sepsis.
Whole transcriptome sequencing reveals neutrophils’ transcriptional landscape associated with active tuberculosis
Authors: Geng Xingzhu , Wu Xiaolin , Yang Qianting , Xin Henan , Zhang Bin , Wang Dakuan , Liu Liguo , Liu Song , Chen Qi , Liu Zisen , Zhang Mingxia , Pan Shouguo , Zhang Xiaobing , Gao Lei , Jin Qi
Published: August 2022

Neutrophils have been recognized to play an important role in the pathogenesis of tuberculosis in recent years. Interferon-induced blood transcriptional signatures in ATB are predominantly driven by neutrophils. In this study, we performed global RNA-seq on peripheral blood neutrophils from active tuberculosis patients (ATB, n=15); latent tuberculosis infections (LTBI, n=22); and healthy controls (HC, n=21). The results showed that greater perturbations of gene expression patterns happened in neutrophils from ATB individuals than HC or those with LTBI, and a total of 344 differentially expressed genes (DEGs) were observed. Functional enrichment analysis showed that besides the interferon signaling pathway, multiple pattern recognition receptor pathways were significantly activated in ATB, such as NOD-like receptors and Toll-like receptors. Meanwhile, we also observed that the expression of genes related to endocytosis, secretory granules, and neutrophils degranulation were downregulated. Our data also showed that the NF-κB signaling pathway might be inhibited in patients with ATB, which could increase Mycobacterium tuberculosis survival and lead to active tuberculosis status. Furthermore, we validated the accuracy of some differentially expressed genes in an independent cohort using quantitative PCR, and obtained three novel genes (RBM3, CSRNP1, SRSF5) with the ability to discriminate active tuberculosis from LTBI and HC.
Identification and verification of YBX3 and its regulatory gene HEIH as an oncogenic system: A multidimensional analysis in colon cancer
Authors: Sun Yiming , Li Zhixi , Wang Wensheng , Zhang Xiuyang , Li Wenjing , Du Guangsheng , Yin Jiuheng , Xiao Weidong , Yang Hua
Published: August 2022

The novel gene YBX3 is important for regulating translation and RNA catabolism and encodes a protein with a highly conserved cold-shock domain. However, its pathogenic roles across cancers (e.g., colon cancer) and its regulation remain unclear. We identified the pathogenic roles of YBX3 and its regulatory lncRNA HEIH in various cancers and investigated their effects on tumor progression in colon cancer. Methods including RNA pull-down, MS, and TMA of 93 patients, qPCR of 12 patients with diverse clinicopathologic stages, and western blotting were performed. The pancancer analysis showed that YBX3 expression varies significantly among not only cancer types but also molecular and immune subtypes of the same cancer. Furthermore, its expression in colon cancer is clinically significant, and there is an obvious negative regulatory association between HEIH and YBX3. Among various cancers, especially colon cancer, YBX3 is more related than HEIH expression to the clinical features and prognosis of subgroups. The receiver operating characteristic analysis showed that HEIH and YBX3 have similar predictive capacity in various cancers. The analysis of differentially expressed genes in colon cancer revealed that they have similar hub gene networks, indicating an oncogenic system with a strong overlap. The results also suggest that YBX3 is associated with tumor immune evasion via different mechanisms involving T-cell exclusion in different cancer types and by the tumor infiltration of immune cells. Interestingly, scRNA-seq revealed that HEIH inhibits this phenomenon. Our results also suggest that YBX3 expression is associated with immune or chemotherapeutic outcomes in various cancers, and YBX3 exhibited a higher predictive power than two of seven standardized biomarkers for response outcomes and overall survival of immune checkpoint blockade subcohorts. In colon cancer cell lines, lncRNA-HEIH and YBX3 associate. MS confirmed that YBX3 was pulled down with HEIH, and western blot showed that HEIH knockdown disinhibited YBX3. This study strongly suggests that lncRNA-HEIH/YBX3 is a pancancer immune-oncogenic system and could serve as a biomarker for diagnosis and prognosis and as a therapeutic target, especially in colon cancer.