Miracle-dz/UniFAR-FTUs huggingface dataset:
Hallmarks of Resistance to Immune-Checkpoint Inhibitors

Abstract Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective in patients with immune-responsive tumors. Most patients with cancer either do not respond to ICIs at all or experience disease progression after an initial period of response. Treatment resistance to ICIs remains a major challenge and defines the biggest unmet medical need in oncology worldwide. In a collaborative workshop, thought leaders from academic, biopharma, and nonprofit sectors convened to outline a resistance framework to support and guide future immune-resistance research. Here, we explore the initial part of our effort by collating seminal discoveries through the lens of known biological processes. We highlight eight biological processes and refer to them as immune resistance nodes. We examine the seminal discoveries that define each immune resistance node and pose critical questions, which, if answered, would greatly expand our notion of immune resistance. Ultimately, the expansion and application of this work calls for the integration of multiomic high-dimensional analyses from patient-level data to produce a map of resistance phenotypes that can be utilized to guide effective drug development and improved patient outcomes.
Transfer pricing in the Saudi Arabia oil and gas sector | NOVA. The University of Newcastle's Digital Repository

his study examines transfer pricing behaviour for the purpose of shifting profits between national tax jurisdictions with different rates of profit tax in the context of the Saudi oil and gas sector as well as that of several other countries (i.e., Australia, Canada, Czech Republic, France, Korea, Japan, Kuwait, Norway, Poland, Sweden, UK and US). The methodology of the Bartelsman and Beetsma (2003) is proposed as the basis for testing the hypothesis. The results of this study show that the Bartelsman and Beetsma (2003) model when applied to the Saudi Arabia oil and gas sector does not detect transfer pricing behaviour for the purpose of shifting profit. However, the Bartelsman and Beetsma (2003) model when applied to other countries such as Japan, Korea, Norway, Poland, and the United Kingdom does show results that suggests the presence of transfer pricing behaviour for the purpose of shifting profits.
Cryo-EM structures of staphylococcal IsdB bound to human hemoglobin reveal the process of heme extraction

Significance During infection, the human pathogen Staphylococcus aureus expresses a surface-exposed receptor, Iron surface determinant B (IsdB), that captures free human hemoglobin (Hb) and removes heme to retrieve iron, an essential nutrient for bacterial proliferation inside the host. Using single-particle cryo-electron microscopy, we solved the structure of two complexes between Hb and IsdB that represent snapshots of the initial interaction, where heme is still bound to Hb, and the final complex after completion of heme extraction. The structural and dynamic details unlocked through these structures will boost the design of inhibitors of IsdB:Hb interaction that might work as innovative antimicrobials.
Using e‐learning tools in biochemistry teaching for undergraduate medical students in multicultural environment in Ukraine during COVID‐19 crisis

Through the special situation like the COVID‐2019 lockdown, interactive techniques play a prime role in the study process. The strategy of lockdown ways of higher education was provided in Ukraine as well as in other countries since March 2020. Our investigation was performed at the Department of Biochemistry and Medical Chemistry of Dnipro State Medical University during the first lockdown of COVID‐19 from March to June 2020. The main aim of the research was the evaluation of the students' attitudes to studying Biochemistry using Google classrooms and Moodle. Four hundred and sixty‐three students studying in English, French, and Ukrainian took part in the survey. Our results reveal that majority of the students found Google classrooms and Moodle as useful e‐learning tools. However, questions dealing with the technical issues of using the Google classrooms on laptops and mobile phones and submitting the replies to the Google classrooms cause difficulties among the students.
Impact of staffing levels and resources of intensive care units on compliance to standard mechanical ventilator guidelines: A city‐wide study in times of COVID‐19 pandemic

Abstract Introduction The COVID‐19 pandemic has affected millions and resulted in a considerable strain on healthcare systems around the world. Intensive care units (ICUs) are reported to be affected the most because significant percentage of ICU patients requires respiratory support through mechanical ventilation (MV). This study examines the staffing levels and compliance with a ventilator care bundle in a single city in Pakistan. Methods A cross‐sectional survey of 14 ICUs including medical and surgical ICUs was conducted through a self‐structured questionnaire including a standardized ventilator care bundle. We assessed the compliance of ICU staff to ventilator care bundle and calculated the correlation between staffing patterns with compliance to this bundle. Results The unit response rate was 64% (7/11 hospitals). Across these seven hospitals, there were 14 functional ICUs (7 surgical and 7 medical). The Mean (SD) numbers of beds and ventilators were 8.14 (3.39) and 5.78 (3.68) while the average patient‐to‐nurse and patient‐to‐doctor ratio was 3: 1 and 5:1 respectively. The median ventilator care bundle compliance score was 26 (IQR = 21–28) out of 30, while in medical and surgical ICUs, median scores were 24 (IQR = 19–26) and 28 (IQR = 23–30) respectively. The perceived least compliant component was head elevation in ventilated patients. Correlation analysis revealed that 24 h a day, 7 days a week onsite cover of Advanced Cardiovascular Life Support certified staff was positively correlated with the ventilator care bundle score (r s = 0.654, p value = .011). Similarly, 24‐h cover of senior ICU nurses was significantly correlated with the application of chlorhexidine oral care (r s = 0.676, p value = .008) while routine subglottic aspiration was correlated with the number of doctors (r s = 0.636, p value = .014). Conclusion Our study suggests that ICUs in Peshawar are not well staffed in comparison with international standards and the compliance of ICUs with the ventilator care bundle is suboptimal. We found only a few aspects of ventilator care bundle compliance were related to nursing and medical staffing levels. Relevance to clinical practice Critical care staffs at most of the medical ICUs in Peshawar are not compliant with the standard guidelines for patients on mechanical ventilation. Moreover, the staffing levels at these ICUs are not in accordance with international standards. However, this study suggests that staffing levels may not be the only cause of non‐compliance with standard mechanical ventilator guidelines. There is an urgent need to design and implement a program that can enhance and monitor the quality of nursing care provided to mechanically ventilated patients. Lastly, nurse staffing of ICUs in Pakistan must be increased to enable high quality care and more doctors should be trained in critical care.
Clinical characteristics, activity levels and mental health problems in children with long coronavirus disease: a survey of 510 children

Background: Whether long coronavirus disease pertains to children as well is not yet clear. Methods: The authors performed a survey in children suffering from persistent symptoms since initial infection. A total of 510 children infected between January 2020 and January 2021 were included. Results: Symptoms such as fatigue, headache, muscle and joint pain, rashes and heart palpitations and issues such as lack of concentration and short-term memory problems were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. Conclusion: A better comprehension of long coronavirus disease is urgently needed.
Risk and protective factors for depressive symptoms among the youth living with HIV in Namibia

Background : Namibia has one of the highest HIV prevalence rates among young people living with HIV and AIDS. The study of mental well-being among this vulnerable population is emerging as an important area of public health research. Methods : This study examined how gender, social support, food insecurity, HIV-related stigma, HIV treatment adherence and HIV transmission knowledge are related to depressive symptoms among young people living with HIV in rural northern Namibia. Data were collected from 188 participants from the Zambezi region. Results : The hierarchical regression analysis revealed that being a female infected with HIV, having perceived food insecurity, experiencing more HIV-related stigma and having low levels of social support can exacerbate the severity of depressive symptoms in this sample of Namibian youth. Discussion : Our findings point to the need to expand social support interventions, enhance socio-economic programmes and reduce HIV-related stigma among young people living with HIV, especially those residing in rural, HIV endemic, resource-limited communities in developing countries.
A Concept Analysis of Self-Silencing

Abstract Self-silencing describes the phenomenon of “loss of voice. ” A clear and comprehensive definition of self-silencing is relevant for nursing research and practice to promote a better understanding of detrimental health outcomes that may result from self-silencing. This concept analysis used a modified version of Walker & Avant’s method to identify attributes, antecedents, and consequences of self-silencing. Self-silencing has psychological and sociocultural dimensions that may result in negative health consequences. Directions for research, practice, and policy are included.
Constrained Functional Connectivity Dynamics in Pediatric Surgical Patients Undergoing General Anesthesia

Background: Functional connectivity in cortical networks is thought to be important for consciousness and can be disrupted during the anesthetized state. Recent work in adults has revealed dynamic connectivity patterns during stable general anesthesia, but whether similar connectivity state transitions occur in the developing brain remains undetermined. The hypothesis was that anesthetic-induced unconsciousness is associated with disruption of functional connectivity in the developing brain and that, as in adults, there are dynamic shifts in connectivity patterns during the stable maintenance phase of general anesthesia. Methods: This was a preplanned analysis of a previously reported single-center, prospective, cross-sectional study of healthy (American Society of Anesthesiologists status I or II) children aged 8 to 16 yr undergoing surgery with general anesthesia (n = 50) at Michigan Medicine. Whole-scalp (16-channel), wireless electroencephalographic data were collected from the preoperative period through the recovery of consciousness. Functional connectivity was measured using a weighted phase lag index, and discrete connectivity states were classified using cluster analysis. Results: Changes in functional connectivity were associated with anesthetic state transitions across multiple regions and frequency bands. An increase in prefrontal–frontal alpha (median [25th, 75th]; baseline, 0.070 [0.049, 0.101] vs. maintenance 0.474 [0.286, 0.606]; P < 0.001) and theta connectivity (0.038 [0.029, 0.048] vs. 0.399 [0.254, 0.488]; P < 0.001), and decrease in parietal–occipital alpha connectivity (0.171 [0.145, 0.243] vs. 0.089 [0.055, 0.132]; P < 0.001) were among those with the greatest effect size. Contrary to the hypothesis, connectivity patterns during the maintenance phase of general anesthesia were dominated by stable theta and alpha prefrontal–frontal and alpha frontal–parietal connectivity and exhibited high between-cluster similarity (r = 0.75 to 0.87). Conclusions: Changes in functional connectivity are associated with anesthetic state transitions but, unlike in adults, connectivity patterns are constrained during general anesthesia in late childhood and early adolescence. During the stable maintenance phase of general anesthesia, functional connectivity patterns in the developing brain are relatively static, in contrast to the dynamic structured transitions previously shown in adults. Using conventional methods to measure functional connectivity, the developing brain demonstrated a hyperconnected frontal cortex during the loss of consciousness, maintenance, and emergence periods. This was most marked for frequencies less than 14 Hz and between the prefrontal and frontal regions.
The Age-Dependent Role of Th22, Tc22, and Tc17 Cells in the Severity of Pneumonia in COVID-19 Immunopathogenesis.

Coronavirus disease 2019 (COVID-19) has clinical manifestations ranging from mild symptoms to respiratory failure, septic shock, and multi-organ failure. Lymphocytes are divided into different subtypes based on their cytokine production pattern. In this study, we investigated the role of cytokine expressions of CD4+ T (T helper [Th]1, Th2, Th17, Th22) and CD8+ T cell subtypes (T cytotoxic [Tc]1, Tc2, Tc17, Tc22) in the pathogenesis of COVID-19. Peripheral blood mononuclear cells (PBMCs) were extracted with Ficoll by density gradient centrifugation from blood samples of 180 COVID-19 patients (children and adults) and 30 healthy controls. PBMCs were stimulated with PMA and Ionomycin and treated with Brefeldin A in the fourth hour, and a 10-colored monoclonal antibody panel was evaluated at the end of the sixth hour using flow cytometry. According to our findings, the numbers of Th22 (CD3+, CD4+, and interleukin [IL]-22+) and Tc22 (CD3+, CD8+, IL-22+) cells increased in adult patients regardless of the level of pneumonia (mild, severe, or symptom-free) as compared with healthy controls (p < 0.05). In addition, the number of Tc17 (CD3+, CD8+, and IL-17A+) cells increased in low pneumonia and severe pneumonia groups compared with the healthy controls (p < 0.05). Both IL-22 and IL-17A production decreased during a follow-up within 6 weeks of discharge. Our findings suggest that the increase in only IL-22 expressed Tc22 cells in the 0-12 age group with a general symptom-free course and higher levels of Th22 and Tc22 in uncomplicated adult cases may indicate the protective effect of IL-22. On the contrary, the association between the severity of pneumonia and the elevation of Tc17 cells in adults may reveal the damaging effect of IL-22 when it is co-expressed with IL-17.
Project management : perspective of small and medium-sized construction firms in Ghana

Literature on construction industry has revealed the extent of importance and the need of good project management practice at a site. Efficient compliance of this project management practice by a firm within the construction sector has yielded results such as minimization of waste which turns to maximize returns of the client, ensured fruitful communication among the project teams to avoid rework and accident amongst others. The research explores how project management is practiced within small and medium-sized firms. The paper mainly focused on the execution phase of project management process; thus the construction stage. Further, the study adopted the use of the literature in project management practice primarily. The results showed that the small and medium-sized firms are mostly owned by solely one person who controls and have adapted self-style project management techniques. This nonstandardized project management practice among small and medium firms affect progress and contributes wastage. Statutory provision for small and medium-sized construction firms must be instituted to make the SMEs project management compliant to enhance project success.
Investigation on the vibration and flow instabilities induced by cavitation in a centrifugal pump

Numerical calculations and experimental measurements were carried out in a closed hydraulic test rig to investigate the vibration characteristics and instabilities induced by the development of cavitation in a centrifugal pump. The internal flow characteristics in the impeller and vibration signals at four different positions of the pump system were analyzed during the cavitation process. The results revealed that the occurrence and development of cavitation could be effectively detected by the sudden increase in the intensity of vibration at the testing points. Corresponding relationships were formulated between the occurrence and the development of cavitation and the intensification of the vibration at the measuring locations. It was found out that the virtual incipient for cavitation was much smaller than the traditional “critical” point.
Antioxidant effects of seaweeds and their active compounds on animal health and production – a review

Abstract Natural antioxidants applied as feed additives can improve not only animals’ health and overall performance but also increase their resistance to environmental stress such as heat stress, bad housing conditions, diseases, etc. Marine organisms, for example seaweeds – red, brown, and green macroalgae contain a plethora of biologically active substances, including phenolic compounds, polysaccharides, pigments, vitamins, micro- and macroelements, and proteins known for their antioxidant activity, which can help in the maintenance of appropriate redox status in animals and show pleiotropic effects for enhancing good health, and productivity. The dysregulated production of free radicals is a marked characteristic of several clinical conditions, and antioxidant machinery plays a pivotal role in scavenging the excessive free radicals, thereby preventing and treating infections in animals. Supplementation of seaweeds to animal diet can boost antioxidant activity, immunity, and the gut environment. Dietary supplementation of seaweeds can also enhance meat quality due to the deposition of marine-derived antioxidant components in muscles. The use of natural antioxidants in the meat industry is a practical approach to minimize or prevent lipid oxidation. However, overconsumption of seaweeds, especially brown macroalgae, should be avoided because of their high iodine content. An important point to consider when including seaweeds in animal feed is their variable composition which depends on the species, habitat, location, harvest time, growing conditions such as nutrient concentration in water, light intensity, temperature, etc. This review highlights the beneficial applications of seaweeds and their extracted compounds, which have antioxidant properties as feed additives and impact animal health and production.
Social stress, performance after-effects and extra-role behaviour

Abstract The article is concerned with the after-effects of social stress on work performance. In a lab-based experiment, seventy participants were assigned to either a stress condition or a no-stress condition. In the stress condition, participants received fake negative performance feedback and they were ostracised by two confederates of the experimenter. Participants carried out the following tasks: attention and divergent creativity. The effects of social stress were examined at three levels: performance after-effects on unscheduled probe tasks, extra-role behaviour and subjective operator state. The manipulation check confirmed that participants experienced social stress. The results showed after-effects of social stress for some forms of extra-role behaviour (i.e. spontaneous reactions) and for the accuracy component of attention. Furthermore, social stress was found to increase negative affect and to reduce self-esteem. The findings point to the importance of assessing different types of after-effects rather than limiting the methodological approach to instant effects on performance. Practitioner summary: The study aimed to examine the multiple effects of social stress. Social stress resulted in increased negative affect and lower self-esteem. Furthermore, social stress was found to reduce the propensity of humans to show extra-role behaviour (i.e. providing spontaneous help to others).
An Efficient Lentiviral-based Proteomics Approach Identifies Mitochondrial Complexes with Neurodegenerative Function

i ACKNOWLEDGMENTS . ii TABLE OF CONTENTS . iii LIST OF TABLES . vi LIST OF FIGURES . vii LIST OF ABBREVIATIONS . ix CHAPTER ONE: INTRODUCTION . 1 1.1 Mitochondria: structure, cellular activities, and role in health and disease. 1 1.2 Previous studies paved the way to implement AP-MS for the large scale study of ND-linked MPs . 4 1.3 Key NDs and the intercepted biological pathways . 5 1.4 Research objectives . 8 CHAPTER TWO: EXPERIMENTAL METHODLOGY . 10 2.1 Materials . 10 2.2 Methods . 10 2.2.1 Human cell lines . 10 2.2.2 Plasmid construction . 16 2.2. 3 Creating ND-linked mitochondrial fusion proteins . 16 2.2. 4 Generation of stable cell lines and immunoblotting . 18
Is there a role for small molecule metabolite biomarkers in the development of a diagnostic test for endometriosis?

Abstract Endometriosis is a disease defined by the presence of benign lesions of endometrial-like glands and stroma outside the endometrial cavity. Affecting an estimated 11.4% of Australian women, symptoms include chronic pelvic pain, dysmenorrhea and infertility. The current gold standard of diagnosis requires an expensive and invasive laparoscopic surgery, resulting in delayed time to treatment. The identification of a non-invasive endometriosis biomarker – a measurable factor correlating with disease presence or activity – has therefore become a priority in endometriosis research, although no biomarker has yet been validated. As small molecule metabolites and lipids have emerged as a potential focus, this review with systematic approach, aims to summarize studies examining metabolomic biomarkers of endometriosis in order to guide future research. EMBASE, PubMed and Web of Science were searched using keywords: lipidomics OR metabolomics OR metabolome AND diagnostic tests OR biomarkers AND endometriosis, and only studies written in English from August 2000 to August 2020 were included. Twenty-nine studies met inclusion and exclusion criteria and were included. These studies identified potential biomarkers in serum, ectopic tissue, eutopic endometrium, peritoneal fluid, follicular fluid, urine, cervical swabs and endometrial fluid. Glycerophospholipids were identified as potential biomarkers in all specimens, except urine and cervical swab specimens. However, no individual molecule or metabolite combination has reached clinical diagnostic utility. Further research using large study populations with robust patient phenotype and specimen characterisation is required if we are to make progress in identifying and validating a non-invasive diagnostic test for endometriosis.