Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of autophagy in sepsis-induced skeletal muscle dysfunction, whole-body metabolism, and survival

Septic patients frequently develop skeletal muscle wasting and weakness, resulting in severe clinical consequences and adverse outcomes. Autophagy is a stress-induced degradative process essential to cell survival. Recent studies have demonstrated that sepsis triggers sustained induction of autophagy in skeletal muscles, although the impact of this enhanced autophagy on sepsis-induced muscle dysfunction remains unclear. Atg7 is an autophagy gene that plays a major role in autophagosome formation. Using an inducible and muscle-specific Atg7 knockout mouse model (Atg7iSkM-KO), we investigated the functional importance of skeletal muscle autophagy in sepsis. Sepsis was induced using cecal ligation and perforation (CLP) with a sham operation serving as a control. Atg7iSkM-KO mice exhibited a more severe phenotype in response to sepsis, marked by severe muscle wasting and contractile dysfunction, hypoglycemia, higher ketone levels and a decreased in survival as compared to mice with intact Atg7. Several genes that encode 26S proteasome subunits were upregulated, suggesting that activation of the ubiquitin-proteasome system is responsible for the severe muscle atrophy that was seen in these mice. Sepsis and Atg7 deletion resulted in the accumulation of mitochondrial dysfunction, although sepsis did not further worsen mitochondrial dysfunction in Atg7iSkM-KO mice. Overall, our study demonstrates that autophagy inactivation in skeletal muscles triggers significant worsening of sepsis-induced contractile and metabolic dysfunctions and negatively impacts survival. Induction of autophagy in skeletal muscles in response to sepsis thus represents a protective mechanism.
Retinal degeneration: Multilevel protection of photoreceptor and ganglion cell viability and function with the novel PKG inhibitor CN238

Hereditary retinal degeneration (RD) is often associated with excessive cGMP-signaling in photoreceptors. Previous research has shown that inhibition of cGMP-dependent protein kinase G (PKG) can slow down the loss of photoreceptors in different RD animal models. In this study, we identified a novel PKG inhibitor, the cGMP analogue CN238, with strong protective effects on photoreceptors in retinal degeneration rd1 and rd10 mutant mice. In long-term organotypic retinal explants, CN238 preserved rd1 and rd10 photoreceptor viability and function. Surprisingly, in explanted retinae CN238 also protected retinal ganglion cells from axotomy induced retrograde degeneration and preserved their functionality. Together, these results confirm the strong neuroprotective capacity of PKG inhibitors for both photoreceptors and retinal ganglion cells, thereby significantly broadening their potential applications for the treatment of retinal diseases and possibly neurodegenerative diseases in general.
The role of psychological empowerment on human resource-related performance outcomes among Generation Y employees in the hotel industry in Sri Lanka

Abstract This paper empirically examines the role of psychological empowerment on human resource-related performance outcomes among Generation Y employees in the hotel industry in Sri Lanka. Data were gathered from 254 Generation Y employees in 67 hotels using a structured questionnaire. These data reveal a significant positive relationship between psychological empowerment and human resource outcomes, except for turnover intention. The findings provide crucial insights for hotel managers as they design empowerment structures and strategies to heighten human resource-related performance outcomes that may lead to competitive advantage. This study is limited to Generation Y employees in the hotel industry in Sri Lanka.
Investigation on the Settlement of High Rockfill Embankment Using Centrifuge Tests

To study the deformation behavior of the high rockfill (HRF) embankment during construction and operation, based on more than a 50-m high rockfill embankment of the second-class road reconstruction project from Xunyang to Ankang of the national road 316 in Shaanxi, China, the centrifuge model test was performed to study the deformation laws of HRF embankment. The test results showed the following: (i) the HRF embankment was stable during construction and operation; (ii) during construction, the settlement occurred at the embankment top, and uplift occurred at the slope foot. Moreover, the deformation at the top was greater than that at the slope foot, and the deformations at both the top and the slope toe reached the maximum value at the end of construction; (iii) during operation, the settlement at the embankment top continued, and it changed rapidly at the start of operation. And then, the rate of the settlement slowed down and reached a steady state finally. The deformation of the slope foot was very small. This study can provide basis and reference for the design and construction of a similar project in mountain areas.
Altered Cerebrospinal Fluid Clearance and Increased Intracranial Pressure in Rats 18 h After Experimental Cortical Ischaemia

Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow.
RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation

RUNX1 is a Runt family transcription factor that plays a critical role in normal hematopoiesis, including the differentiation and proliferation of hematopoietic cells. RUNX1 mutations, including chromosomal translocations, cause abnormal cell differentiation, but the mutation alone is not sufficient to cause leukemia. In MLL-fusion-induced leukemia, dysregulated wild-type RUNX1 can promote leukemia survival. Nevertheless, the underlying mechanisms of dysregulated wild-type RUNX1 in leukemia development have not been fully elucidated. This study overexpressed and knocked down RUNX1 expression in THP-1 human leukemia cells and CD34+ hematopoietic stem/progenitor cells to investigate the biological functions affected by dysregulated RUNX1. Our data indicated RUNX1 facilitated proliferation to promote leukemia cell growth. Furthermore, we demonstrated that RUNX1 knockdown in leukemia cells drastically diminished colony-forming ability. Finally, the RUNX1-knocked down cell depletion phenotype could be rescued by overexpression of CENPE, a cell proliferation gene and a RUNX1 direct target gene. Our results indicate a possible mechanism involving the RUNX1-CENPE axis on promoting leukemic cell growth.
Poor Prognosis and Therapeutic Responses in LILRB1-Expressing M2 Macrophages-Enriched Gastric Cancer Patients

Immunosuppressive molecules are valuable prognostic biomarkers across different cancer types. Leukocyte immunoglobulin like receptor subfamily B1 (LILRB1) is considered to be an immunosuppressive molecule, which is an important receptor of human leukocyte antigen G. However, the clinical significance of LILRB1 expression in gastric cancer remains unexplored. We analyzed the immunohistochemistry data of 166 gastric cancer patients to determine the clinicopathologic and survival significance of LILRB1. Immunofluorescence was conducted to detect the co-localization of LILRB1 with infiltrating immune cells. Additionally, we also assessed the immune contexture, immune cell functions and tumor microenvironment state related to LILRB1. We found that LILRB1 was mainly present in tumor stroma which was higher in tumor tissues compared with matched adjacent tissues. High-LILRB1 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis showed that LILRB1 had a significant positive correlation with M2 tumor-associated macrophages (TAMs) infiltration. Immunofluorescence confirmed that M2 TAMs were the primary immune cells expressing LILRB1. Dense infiltration of LILRB1+ M2 TAMs yielded an immunosuppressive microenvironment manifested as enriched exhausted CD8+ T cells and increased immunosuppressive cytokines. Moreover, patients with high infiltration of both LILRB1+ cells and M2 TAMs indicated poor prognosis and inferior therapeutic responsiveness to adjuvant chemotherapy. In conclusion, LILRB1+ M2 TAMs were associated with a pro-tumor immune contexture and determine poor prognosis in gastric cancer. Further studies are essential to explore therapeutic targeting LILRB1+ M2 TAMs.
The 2019 Universiti Teknologi MARA, Malaysia Staff Survey: Determining the Level and Predictors of Quality of Life

Experiencing good quality of life (QOL) among university staff is extremely crucial to ensuring academic excellence; however, there are limited data on factors that contribute to QOL among university staff. This study aims to determine the level and the predictors for good QOL among university staff. The consenting participants were selected using a stratified sampling method. Participants who had fulfilled the selection criteria were provided with socio-demographic, medical illness, job factor, and family background questionnaires. QOL and psychological well-being (depression, anxiety, and stress) were assessed using the World Health Organization Quality of Life brief version (WHOQOL-BREF) and Depression, Anxiety, and Stress Scale (DASS-21) questionnaires, respectively. A total of 278 staff (mean ± SD age: 38.84 ± 7.85 years, 44.2% males, 82.7% married) had participated in this study. This study found that participants had low QOL in the domains of physical health [P-QOL] (11.2%), psychological health [PSY-QOL] (9.7%), social relationships [SR-QOL] (19.1%), and environment [E-QOL] (14.4%). The predictors of P-QOL were depression, medical illness, and number of dependents, while those of PSY-QOL were work promotion, depression, medical illness, and number of dependents. Additionally, the predictors of SR-QOL were campus location, depression, and work promotion, while those of E-QOL were age, level of education, depression, work promotion, and medical illness. Depression significantly affected all domains of QOL. Younger participants without medical illness and those with tertiary level of education had increased odds of having good QOL. Participants having dependents without work promotion and employed in suburban areas had decreased odds of having good QOL. The relevant authority should be identified and then assist staff with difficulties to ensure the staff benefited from having a good QOL.
Measuring Mind Wandering During Online Lectures Assessed With EEG

Mind wandering can inhibit learning in multimedia classrooms, such as when watching online lectures. One explanation for this effect is that periods of mind wandering cause learners’ attention to be redirected from the learning material toward task-unrelated thoughts. The present study explored the relationship between mind wandering and online education using electroencephalography (EEG). Participants were asked to attend to a 75 minute educational video lecture, while task-irrelevant auditory tones played at random intervals. The tones were of two distinct pitches, with one occurring frequently (80%) and the other infrequently (20%). Participants were prompted at pseudo-random intervals during the lecture to report their degree of experienced mind wandering. EEG spectral power and event-related potentials (ERP) were compared between states of high and low degrees of self-reported mind wandering. Participants also performed pre/post quizzes based on the lecture material. Results revealed significantly higher delta, theta and alpha band activity during mind wandering, as well as a decreased P2 ERP amplitude. Further, learning scores (improvement on quizzes pre to post) were lower among participants who reported higher degrees of mind wandering throughout the video. The results are consistent with a view that mind wandering during e-learning is characterized by a shift in attention away from the external world and toward internal thoughts, which may be a cause of reduced learning.
Caveolin-1 Deficiency Protects Mice Against Carbon Tetrachloride-Induced Acute Liver Injury Through Regulating Polarization of Hepatic Macrophages

Polarization of hepatic macrophages plays a crucial role in the injury and repair processes of acute and chronic liver diseases. However, the underlying molecular mechanisms remain elusive. Caveolin-1 (Cav1) is the structural protein of caveolae, the invaginations of the plasma membrane. It has distinct functions in regulating hepatitis, cirrhosis, and hepatocarcinogenesis. Given the increasing number of cases of liver cancer, nonalcoholic steatohepatitis, and non-alcoholic fatty liver disease worldwide, investigations on the role of Cav1 in liver diseases are warranted. In this study, we aimed to investigate the role of Cav1 in the pathogenesis of acute liver injury. Wild-type (WT) and Cav1 knockout (KO) mice (Cav1tm1Mls) were injected with carbon tetrachloride (CCl4). Cav1 KO mice showed significantly reduced degeneration, necrosis, and apoptosis of hepatocytes and decreased level of alanine transaminase (ALT) compared to WT mice. Moreover, Cav1 was required for the recruitment of hepatic macrophages. The analysis of the mRNA levels of CD86, tumor necrosis factor (TNF), and interleukin (IL)-6, as well as the protein expression of inducible nitric oxide synthase (iNOS), indicated that Cav1 deficiency inhibited the polarization of hepatic macrophages towards the M1 phenotype in the injured liver. Consistent with in vivo results, the expressions of CD86, TNF, IL-6, and iNOS were significantly downregulated in Cav1 KO macrophages. Also, fluorescence-activated cell sorting (FACS) analysis showed that the proportion of M1 macrophages was significantly decreased in the liver tissues obtained from Cav1 KO mice following CCl4 treatment. In summary, our results showed that Cav1 deficiency protected mice against CCl4-induced acute liver injury by regulating polarization of hepatic macrophages. We provided direct genetic evidence that Cav1 expressed in hepatic macrophages contributed to the pathogenesis of acute liver injury by regulating the polarization of hepatic macrophages towards the M1 phenotype. These findings suggest that Cav1 expressed in macrophages may represent a potential therapeutic target for acute liver injury.
Curiosity-Based Interventions Increase Everyday Functioning Score But Not Serum BDNF Levels in a Cohort of Healthy Older Adults

An enriched environment is effective in stimulating learning and memory in animal models as well as in humans. Environmental enrichment increases brain-derived neurotrophic factor (BDNF) in aged rats and reduces levels of Alzheimer-related proteins in the blood, including amyloid-β (Aβ) peptides and misfolded toxic forms of tau. To address whether stimulation of curiosity, which is a form of enrichment, may provide a buffer against Alzheimer’s disease (AD), we measured levels of biomarkers associated with AD at baseline and after a 6-week intervention in older adults (>65 years of age) randomized to one of three different intervention conditions. Specifically, in this pilot study, we tested the effectiveness of a traditional, structured learning environment compared to a self-motivated learning environment designed to stimulate curiosity. There were no significant differences from baseline to post-intervention in any of the groups for Aβ42/Aβ40 ratio or t-tau (total-tau) plasma levels. Serum BDNF levels decreased significantly in the control group. Interestingly, individuals who had the lowest serum BDNF levels at baseline experienced significantly higher increases in BDNF over the course of the 6-week intervention compared to individuals with higher serum BDNF levels at baseline. As expected, older individuals had lower MoCA scores. Years of education correlated negatively with Aβ levels, suggesting a protective effect of education on levels of this toxic protein. ECog scores were negatively correlated with BDNF levels, suggesting that better performance on the ECog questionnaire was associated with higher BDNF levels. Collectively, these findings did not suggest that a 6-week cognitive training intervention focused on curiosity resulted in significant alterations in blood biomarkers but showed interesting correlations between cognitive scores and BDNF levels, further supporting the role of this trophic factor in brain health in older adults.
Case Report: Diagnosis of Myelodysplastic Syndrome in a 72-Year-Old Female With Interstitial Lung Disease

Acute fibrinous and organizing pneumonia (AFOP) is an entity that can be secondary to various conditions leading to lung injury, such as infections, malignancies, and various autoimmune conditions or idiopathic interstitial lung disease, when no obvious underlying cause is identified. Myelodysplastic syndromes (MDS), on the other hand, are a spectrum of clonal myeloid disorders, with a higher risk of acute leukemia, characterized by ineffective bone marrow (BM) hematopoiesis and, thus, peripheral blood (PB) cytopenias. Immune deregulation is thought to take part in the pathophysiology of the disease, including abnormal T and/or B cell responses, innate immunity, and cytokine expression. In the literature, there are a few case reports of patients with MDS that have presented pulmonary infiltrates and were diagnosed as having AFOP or organizing pneumonia (OP). It is rare, though, to have isolated pulmonary infiltrates without Sweet's syndrome or even the pulmonary infiltrates to precede the diagnosis and treatment of MDS, which was our case. We present a 72-year-old female developing new lung infiltrates refractory to antibiotic treatment that responded well to corticosteroids and was histologically described as having OP. The treatment was gradually successfully switched to mycophenolate mofetil (MMF). The patient was later diagnosed with MDS. This interesting case report suggests firstly that a diagnosis of AFOP or OP should alert the clinician to search for an underlying cause including MDS and vice versa, the use of systemic steroids should not be postponed, and, finally, that MMF can successfully be used in these patients.
Multi-Organ Dysfunction in Cerebral Palsy

Cerebral Palsy (CP) describes a heterogenous group of non-progressive disorders of posture or movement, causing activity limitation, due to a lesion in the developing brain. CP is an umbrella term for a heterogenous condition and is, therefore, descriptive rather than a diagnosis. Each case requires detailed consideration of etiology. Our understanding of the underlying cause of CP has developed significantly, with areas such as inflammation, epigenetics and genetic susceptibility to subsequent insults providing new insights. Alongside this, there has been increasing recognition of the multi-organ dysfunction (MOD) associated with CP, in particular in children with higher levels of motor impairment. Therefore, CP should not be seen as an unchanging disorder caused by a solitary insult but rather, as a condition which evolves over time. Assessment of multi-organ function may help to prevent complications in later childhood or adulthood. It may also contribute to an improved understanding of the etiology and thus may have an implication in prevention, interventional methods and therapies. MOD in CP has not yet been quantified and a scoring system may prove useful in allowing advanced clinical planning and follow-up of children with CP. Additionally, several biomarkers hold promise in assisting with long-term monitoring. Clinicians should be aware of the multi-system complications that are associated with CP and which may present significant diagnostic challenges given that many children with CP communicate non-verbally. A step-wise, logical, multi-system approach is required to ensure that the best care is provided to these children. This review summarizes multi-organ dysfunction in children with CP whilst highlighting emerging research and gaps in our knowledge. We identify some potential organ-specific biomarkers which may prove useful in developing guidelines for follow-up and management of these children throughout their lifespan.
Altruistic Giving Toward Refugees: Identifying Factors That Increase Citizens' Willingness to Help

Over the past decade, the world has faced an unprecedented refugee crisis. The large number of incoming refugees represents a challenge for host societies and its citizens triggering reactions from a supportive welcome to brusque rejection and hostile behavior toward refugees. In a pre-registered study, we investigated factors that could promote altruistic behavior in fully incentivized one-shot Dictator Game toward various receiver groups including refugees. We find that host citizens behave more altruistically toward refugees and other receiver groups if they (a) share a local identity with them (i.e., live in the same city), and (b) perceive them to be close (to the self) and warm-hearted. Moreover, citizens that are (c) generally more prosocial and hold a more left-wing political orientation are more willing to give. Unexpectedly, from a theoretical point of view, altruistic giving toward refugees was not influenced in the predicted direction by a shared student identity, competition and perceived income differences (although the latter effect was significant when considering all receiver groups). For shared student identity we even observe a reduction of altruistic behavior, while the opposite effect was predicted. We discuss implications for public policies for successful refugee helping and integration.