bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of C5aR1 alleviates liver inflammation and fibrosis in a mouse model of NASH by regulating TLR4 signaling and macrophage polarization
Authors: Jiang Keqing , Lu Shibang , Li Dongxiao , Liu Mingjiang , Jin Hu , Lei Biao , Wang Sifan , Long Kang , He Songqing , Zhong Fudi
Published: May 2023

Background

Nonalcoholic steatohepatitis (NASH) is an advanced form of chronic fatty liver disease, which is a driver of hepatocellular carcinoma. However, the roles of the C5aR1 in the NASH remain poorly understood. Here, we aimed to investigate the functions and mechanisms of the C5aR1 on hepatic inflammation and fibrosis in murine NASH model.

Methods

Mice were fed a normal chow diet with corn oil (ND + Oil), a Western diet with corn oil (WD + Oil) or a Western diet with carbon tetrachloride (WD + CCl4) for 12 weeks. The effects of the C5a–C5aR1 axis on the progression of NASH were analyzed and the underlying mechanisms were explored.

Results

Complement factor C5a was elevated in NASH mice. C5 deficiency reduced hepatic lipid droplet accumulation in the NASH mice. The hepatic expression levels of TNFα, IL-1β and F4/80 were decreased in C5-deficient mice. C5 loss alleviated hepatic fibrosis and downregulated the expression levels of α-SMA and TGFβ1. C5aR1 deletion reduced inflammation and fibrosis in NASH mice. Transcriptional profiling of liver tissues and KEGG pathway analysis revealed that several pathways such as Toll-like receptor signaling, NFκB signaling, TNF signaling, and NOD-like receptor signaling pathway were enriched between C5aR1 deficiency and wild-type mice. Mechanistically, C5aR1 deletion decreased the expression of TLR4 and NLRP3, subsequently regulating macrophage polarization. Moreover, C5aR1 antagonist PMX-53 treatment mitigated the progression of NASH in mice.

Conclusions

Blockade of the C5a–C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH.
Lumbar puncture-verified subarachnoid hemorrhage: bleeding sources, need of radiological examination, and functional recovery
Authors: Kevci Rozerin , Lewén Anders , Ronne-Engström Elisabeth , Velle Fartein , Enblad Per , Svedung Wettervik Teodor
Published: May 2023

Background

The primary aim was to determine the diagnostic yield of vascular work-up, the clinical course during neurointensive care (NIC), and rate of functional recovery for patients with computed tomography (CT)-negative, lumbar puncture (LP)-verified SAH.

Methods

In this retrospective study, 1280 patients with spontaneous SAH, treated at our NIC unit, Uppsala University Hospital, Sweden, between 2008 and 2018, were included. Demography, admission status, radiological examinations (CT angiography (CTA) and digital subtraction angiography (DSA)), treatments, and functional outcome (GOS-E) at 12 months were evaluated.

Results

Eighty (6%) out of 1280 SAH patients were computed tomography (CT)-negative, LP-verified cases. Time between ictus and diagnosis was longer for the LP-verified SAH cohort in comparison to the CT-positive patients (median 3 vs 0 days, p < 0.001). One fifth of the LP-verified SAH patients exhibited an underlying vascular pathology (aneurysm/AVM), which was significantly less common than for the CT-verified SAH cohort (19% vs. 76%, p < 0.001). The CTA- and DSA-findings were consistent in all of the LP-verified cases. The LP-verified SAH patients exhibited a lower rate of delayed ischemic neurological deficits, but no difference in rebleeding rate, compared to the CT-verified cohort. At 1-year post-ictus, 89% of the LP-verified SAH patients had recovered favorably, but 45% of the cases did not reach good recovery. Having an underlying vascular pathology and an external ventricular drainage were associated with worse functional recovery (p = 0.02) in this cohort.

Conclusions

LP-verified SAH constituted a small proportion of the entire SAH population. Having an underlying vascular pathology was less frequent in this cohort, but still occurred in one out of five patients. Despite the small initial bleeding in the LP-verified cohort, many of these patients did not reach good recovery at 1 year, this calls for more attentive follow-up and rehabilitation in this cohort.
The ‘α-synucleinopathy syndicate’: multiple system atrophy and Parkinson’s disease
Authors: Sian-Hulsmann Jeswinder , Riederer Peter
Published: May 2023

Multiple System Atrophy (MSA) and Parkinson’s diseases (PD) are elite members of the α-synucleinopathy organization. Aberrant accumulations of the protein α-synuclein characterize them. A plethora of evidence indicates the involvement of these rogue inclusions in a cascade of events that disturb cellular homeostasis resulting in neuronal dysfunction. These two neurodegenerative diseases share many features both clinically and pathologically. Cytotoxic processes commonly induced by reactive free radical species have been associated with oxidative stress and neuroinflammation, frequently reported in both diseases. However, it appears they have characteristic and distinct α-synuclein inclusions. It is glial cytoplasmic inclusions in the case of MSA while Lewy bodies manifest in PD. This is probably related to the etiology of the illness. At present, precise mechanism(s) underlying the characteristic configuration of neurodegeneration are unclear. Furthermore, the “prion-like” transmission from cell to cell prompts the suggestion that perhaps these α-synucleinopathies are prion-like diseases. The possibility of some underlying genetic foul play remains controversial. But as major culprits of pathological processes or even single triggers of PD and MSA are the same—like oxidative stress, iron-induced pathology, mitochondriopathy, loss of respiratory activity, loss of proteasomal function, microglial activation, neuroinflammation—it is not farfetched to assume that in sporadic PD and also in MSA a variety of combinations of susceptibility genes contribute to the regional specificity of pathological onset. These players of pathology, as mentioned above, in a synergistic combination, are responsible for driving the progression of PD, MSA and other neurodegenerative disorders. Elucidating the triggers and progression factors is vital for advocating disease modification or halting its progression in both, MSA and PD.
Rainfall changes perceived by farmers and captured by meteorological data: two sides to every story
Authors: Hubertus Lena , Groth Juliane , Teucher Mike , Hermans Kathleen
Published: May 2023

Subsistence farmers with high dependency on natural resources are exceptionally vulnerable to rainfall changes. Besides, they are in the front row when it comes to observing these changes. Studies that systematically investigate similarities and differences between measured and perceived rainfall changes are typically limited to trends in rainfall amounts, thereby disregarding changes in extreme events, rainy season durations, and timing. We address this gap by contrasting rainfall changes perceived by subsistence farmers in the Ethiopian highlands with meteorological daily rainfall data derived from the Climate Hazards Group Infrared Precipitation with Stations (CHIRPS). We applied nine distinct metrics for rainfall dynamics, accounting for rainfall variability, including extreme events and changes in the onset and cessation of the two rainy seasons. Farmers perceived increasingly unreliable rainfall for both the short and the long rainy seasons, with later onset and earlier cessation, increasing rainfall intensity, and increasing occurrence of untimely rainfall and droughts. This partially disagrees with the CHIRPS data that indicate most significant rainfall changes for the short rainy season only. Since the early 1980s, this season has been experiencing decreasing rainfall amounts, with high variability between years and an increasingly uncertain – yet delayed – onset. In contrast, the long rainy season experienced little changes in rainfall. Our results point towards changing farmers' water availability and water demand as an explanation for the perceived deteriorating rainfall conditions. As farmers’ perceptions partly diverge from meteorological observations, both data sources should be used complementarily to improve our understanding of climatic change.
RETRACTED ARTICLE: Circular RNA circDLG1 contributes to HCC progression by regulating the miR-141-3p/WTAP axis
Authors: Wang Qian , Yu Wei , Wang Tao , Huang Changshan
Published: May 2023

This study aims to explore novel and reliable biomarkers for predicting hepatocellular carcinoma (HCC) prognosis. Circular RNAs (circRNAs) were determined by analysis of human circRNA arrays and quantitative reverse transcription polymerase reactions. To test for an interaction between circDLG1, we used luciferase reporter assays, RNA immunoprecipitation, and fluorescence in situ hybridization assays that were employed to test the interaction between circDLG1, miR-141-3p, and WTAP. q-RT-PCR and western blot were used to evaluate the target regulation of miR-141-3p and WTAP. shRNA-mediated knockdown of circDLG1, proliferation, migration, and invasion experiment of metastasis were used to evaluate the function of circDLG. CircDLG1 rather than lining DLG1 was upregulated in HCC tissues, from HCC patients as well as HCC cell lines compared to normal controls. circDLG1 high expression in HCC patients was correlated with shorter overall survival. Knockdown of circDLG1 and miR-141-3p mimic could inhibit the tumorigenesis of HCC cells in vivo and in vitro. Importantly, we demonstrated that circDLG1 could act as a sponge of miR-141-3p to regulate the expression of WTAP, and further suppress the tumorigenesis of HCC cells. Our study reveals that circDLG1 can serve as a novel potential circulating biomarker for the detection of HCC. circDLG1 participates in the progression of HCC cells by sponging miR-141-3p with WTAP, providing new insight into the treatment of HCC.
The effects of mindfulness-based interventions in medical students: a systematic review
Authors: Kaisti Ilona , Kulmala Petri , Hintsanen Mirka , Hurtig Tuula , Repo Saara , Paunio Tiina , Miettunen Jouko , Halt Anu-Helmi , Jääskeläinen Erika
Published: May 2023

The number of studies on the effects of mindfulness on healthcare professionals is increasing. The main aim of this study was to collate the quantitative results of original studies analyzing the effects of mindfulness-based interventions on a variety of outcomes in medical students. We also analyzed how the study design and characteristics of the intervention affect the results, and identified qualitative effects of mindfulness interventions. A literature search was performed in different databases in June 2020. Original articles meeting the following criteria were included: (1) at least 50% of the participants were medical students, (2) included a mindfulness intervention, (3) analyzed any outcome relating to mindfulness intervention, (4) peer-reviewed (5) written in English. Eventually, 31 articles including 24 different samples were included. Over half of the studies were RCTs. In over half of the studies, the intervention was 4- to 10-week original Mindfulness-Based Stress Reduction or Mindfulness-Based Cognitive Therapy or a modification of these. In general, satisfaction with the interventions was good. Based on a meta-analysis, after the intervention, the intervention group had statistically significantly fewer symptoms of stress and distress and had higher mindfulness than the controls. The beneficial effects persisted in follow-ups over months or years. Both long and shorter courses and courses with and without face-to-face sessions were effective. Both controlled and uncontrolled studies had statistically significant results. Qualitative results revealed potential factors behind the quantitative effects. The number of studies on mindfulness interventions in medical students has increased drastically. Mindfulness-based interventions seem to offer a good possibility to enhance medical students’ well-being.
Is Biofeedback for Vertigo Effective in Ordinary Medical Centers? A Controlled Trial in Northern Italy
Authors: Buizza Chiara , Franco Elena , Ghilardi Alberto
Published: May 2023

The aim of this study was to assess the therapeutic effectiveness of biofeedback, in a medical center’s routine for treating vestibular disorders, reducing emotional, functional, and physical disability at three-month follow-up. A total of 197 outpatients were recruited from a medical center to treat vestibular disorders. Patients in the control group received treatment as usual, consisting of one monthly visit with an otolaryngologist and pharmacological treatment specific for vertigo, while the experimental group attended biofeedback training. Patients in the experimental group received pharmacological therapy only in the phase before the start of biofeedback in order to stabilize the acute phase. During the three-month follow-up, the experimental group did not receive any booster sessions of biofeedback. At three-month follow-up there was a statistically significant difference between the groups, both in the mean total score of the dizziness handicap inventory and in the three subscales: physical, emotional, and functional. Moreover, the biofeedback group had reduced psycho-physiological parameters for all average values at three-month follow-up compared to the baseline. This is one of few studies assessing the effectiveness of biofeedback in a naturalistic setting for vestibular disorder treatment. The data confirmed that biofeedback can impact illness course, in terms of self-perceived disability reduction, assessed on emotional, functional, and physical aspects of daily living.
Plasma ESR1 mutations and outcome to first-line paclitaxel and bevacizumab in patients with advanced ER-positive/HER2-negative breast cancer
Authors: Bos M. K. , Lam S. W. , Motta G. , Helmijr J. C. A. , Beaufort C. M. , de Jonge E. , Martens J. W. M. , Boven E. , Jansen M. P. H. M. , Jager A. , Sleijfer S.
Published: May 2023

Background

ESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients.

Methods

ESR1 mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm, N = 91) in the randomized phase II ATX study. Samples collected at baseline (n = 51) and at cycle 2 (n = 13, C2) were analyzed using a breast cancer next-generation sequencing panel. This study was powered to detect a benefit in progression-free survival (PFS) at six months for patients treated with paclitaxel/bevacizumab compared to historical trials with fulvestrant. PFS, overall survival (OS), and ctDNA dynamics were exploratory analyses.

Results

PFS at six months was 86% (18/21) in patients with an ESR1 mutation detected and 85% (23/27) in wildtype ESR1 patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6–8.8] for ESR1 mutant patients versus 8.7 months [95% confidence interval (CI), 8.3–9.2] for ESR1 wildtype patients [p = 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6–33.7] for ESR1 mutant patients versus 28.1 months [95% confidence interval (CI), 19.3–36.9] for ESR1 wildtype patients [p = 0.27]. Patients with ≥ two ESR1 mutations had a significantly worse OS, but not PFS, compared to those who did not [p = 0.003]. Change in ctDNA level at C2 was not different between ESR1 and other mutations.

Conclusions

Presence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.
Inter-placental variability is not a major factor affecting the healing efficiency of amniotic membrane when used for treating chronic non-healing wounds
Authors: Horvath Vojtech , Svobodova Alzbeta , Cabral Joao Victor , Fiala Radovan , Burkert Jan , Stadler Petr , Lindner Jaroslav , Bednar Jan , Zemlickova Martina , Jirsova Katerina
Published: May 2023

This study aimed to evaluate the efficacy of cryopreserved amniotic membrane (AM) grafts in chronic wound healing, including the mean percentage of wound closure per one AM application, and to determine whether the healing efficiency differs between AM grafts obtained from different placentas. A retrospective study analyzing inter-placental differences in healing capacity and mean wound closure after the application of 96 AM grafts prepared from nine placentas. Only the placentas from which the AM grafts were applied to patients suffering from long-lasting non-healing wounds successfully healed by AM treatment were included. The data from the rapidly progressing wound-closure phase (p-phase) were analyzed. The mean efficiency for each placenta, expressed as an average of wound area reduction (%) seven days after the AM application (baseline, 100%), was calculated from at least 10 applications. No statistical difference between the nine placentas’ efficiency was found in the progressive phase of wound healing. The 7-day average wound reduction in particular placentas varied from 5.70 to 20.99% (median from 1.07 to 17.75) of the baseline. The mean percentage of wound surface reduction of all analyzed defects one week after the application of cryopreserved AM graft was 12.17 ± 20.12% (average ± SD). No significant difference in healing capacity was observed between the nine placentas. The data suggest that if there are intra- and inter-placental differences in AM sheets’ healing efficacy, they are overridden by the actual health status of the subject or even the status of its individual wounds.
The spatial variation and driving factors of soil total carbon and nitrogen in the Heihe River source region
Authors: Tong Shan , Cao Guangchao , Zhang Zhuo , Zhang Jinhu
Published: May 2023

Soil carbon and nitrogen levels are key indicators of soil fertility and are used to assess ecological value and safeguard the environment. Previous studies have focused on the contributions of vegetation, topography, physical and chemical qualities, and meteorology to soil carbon and nitrogen change, but there has been little consideration of landscape and ecological environment types as potential driving forces. The study investigated the horizontal and vertical distribution and influencing factors of total carbon and total nitrogen in soil at 0–20 and 20–50 cm depths in the source region of the Heihe River. A total of 16 influencing factors related to soil, vegetation, landscape, and ecological environment were selected, and their individual and synergistic effects on the distributions of total carbon and total nitrogen in soil were assessed. The results show gradually decreasing average values of soil total carbon and total nitrogen from the surface layer to the bottom layer, with larger values in the southeast part of the sampling region and smaller values in the northwest. Larger values of soil total carbon and total nitrogen at sampling points are distributed in areas with higher clay and silt and lower soil bulk density, pH, and sand. For environmental factors, larger values of soil total carbon and total nitrogen are distributed in areas with higher annual rainfall, net primary productivity, vegetation index, and urban building index, and lower surface moisture, maximum patch index, boundary density, and bare soil index. Among soil factors, soil bulk density and silt are most closely associated with soil total carbon and total nitrogen. Among surface factors, vegetation index, soil erosion, and urban building index have the greatest influence on vertical distribution, and maximum patch index, surface moisture, and net primary productivity have the greatest influence on horizontal distribution. In conclusion, vegetation, landscape, and soil physical properties all have a significant impact on the distribution of soil carbon and nitrogen, suggesting better strategies to improve soil fertility.
EGF-receptor phosphorylation and downstream signaling are activated by genistein during subacute liver damage
Authors: Ayala-Calvillo Erick , Rodríguez-Fragoso Lourdes , Álvarez-Ayala Elizabeth , Leija-Salas Alfonso
Published: May 2023

The epidermal growth factor receptor (EGFR) plays an important role on hepatic protection in acute and chronic liver injury. The aim of this study was to investigate the role of genistein on EGFR expression, phosphorylation and signaling pathways in experimental subacute liver damage induced by carbon tetrachloride (CCl4). We used male Wistar rats that were randomly divided into four groups: (1) Control; (2) Genistein 5 mg/kg per oral; (3) Subacute liver damage induced by CCl4 4 mg/kg subcutaneously; and (4) Animals received CCl4 and genistein at the dosage indicated. The effect of genistein on EGFR expression, phosphorylation and signaling pathways were investigated by western blot and densitometric analyses. Histological changes were evaluated on slices stained with Hematoxylin-Eosin and Masson´s trichromic, as well as an immunohistochemical analysis for proliferating cell nuclear antigen (PCNA). Additionally, pro-inflammatory cytokines and liver enzymes were quantified. Our study showed that genistein increased EGFR expression, EGFR-specific tyrosine residues phosphorylation (pY1068-EGFR and pY84-EGFR), signal transducer and activator of transcription phosphorylation (pSTAT5), protein kinase B phosphorylation (pAKT) and PCNA in animals with CCl4-induced subacute liver damage. It was found a significant reduction of pro-inflammatory cytokines in serum from animals with subacute liver damage treated with genistein. Those effects were reflected in an improvement in the architecture and liver function. In conclusion, genistein can induce a transactivation of EGFR leading to downstream cell signaling pathways as early events associated with regeneration and hepatoprotection following subacute liver damage.
Empowered to Stay Active: Psychological Empowerment, Retirement Timing, and Later Life Work
Authors: Drazic Ivana , Schermuly Carsten C. , Büsch Victoria
Published: May 2023

Motivating older employees both to prolong their working lives and to stay active even after retirement has become increasingly important due to rising old-age dependency ratios. Later life work—including both paid work and volunteering—has thus become an important topic for scholars and practitioners. We aim to extend research on later life work by hypothesizing that psychological empowerment at work increases not only desired and actual retirement ages but also levels of later life work. Second, we test differential effects of psychological empowerment on later life work, expecting it to be more strongly related to paid work after retirement (i.e., bridge employment) than to volunteering. Third, we suggest that the relationship between psychological empowerment and bridge employment depends on the employees’ level of physical limitations. We used data from a longitudinal panel study in Germany in which structured telephone interviews were conducted. A sample of older individuals who had retired between two waves of measurement was drawn (time lag: three years; n = 210). The results of a path analysis support the postulated mediation. Furthermore, as expected, psychological empowerment more accurately predicted bridge employment than volunteering, and physical limitations moderated the relationship between psychological empowerment and bridge employment. Lastly, additional analyses on the individual empowerment facets revealed that only the competence facet played a significant role in the proposed hypotheses. Overall, our findings suggest that psychological empowerment may help to increase older employees’ motivation to delay retirement and to stay active even after retirement.
Antiviral and protective effect of small interfering RNAs against rift valley fever virus in vitro
Authors: Ahmed Engy. M. , Boseila Abeer. A. , Hanora Amro S. , Solyman Samar. M.
Published: May 2023

Background

Rift Valley Fever Virus (RVFV) is an arbovirus, a zoonotic disease that resurfaces as a potential hazard beyond geographic boundaries. Fever that can proceed to encephalitis, retinitis, hemorrhagic fever, and death is the main manifestation observed in human infections. RVFV has no authorized medication. The RNA interference (RNAi) gene silencing pathway is extremely well conserved. By targeting specific genes, small interfering RNA (siRNA) can be used to suppress viral replication. The aim of this study was to design specific siRNAs against RVFV and evaluate their prophylactic and antiviral effects on the Vero cells.

Methods and results

Various siRNAs were designed using different bioinformatics tools. Three unique candidates were tested against an Egyptian sheep cell culture-adapted strain BSL-2 that suppressed RVFV N mRNA expression. SiRNAs were transfected a day before RVFV infection (pre-transfection), and 1 h after the viral infection (post-transfection), and were evaluated to detect the silencing activity and gene expression decrease using real-time PCR and a TCID50 endpoint test. The degree of N protein expression was determined by western blot 48 h after viral infection. D2 which targets the (488–506 nucleotides), the middle region of RVFV N mRNA was the most effective siRNA at 30 nM concentration, it almost eliminates N mRNA expression when utilized as antiviral or preventive therapy. siRNAs had a stronger antiviral silencing impact when they were post-transfected into Vero cells.

Conclusion

Pre and post-transfection of siRNAs significantly reduced RVFV titer in cell lines, offering novel and potentially effective anti-RVFV epidemics and epizootics therapy.
Resveratrol as a circadian clock modulator: mechanisms of action and therapeutic applications
Authors: Spaleniak Weronika , Cuendet Muriel
Published: May 2023

In the past decades, resveratrol has gained increasing attention due to its versatile and beneficial properties. This natural polyphenol, commonly present in the human diet, has been shown to induce SIRT1 and to modulate the circadian rhythm at the cellular and organismal levels. The circadian clock is a system regulating behavior and function of the human body, thus playing a crucial role in health maintenance. It is primarily entrained by light-dark cycles; however, other factors such as feeding-fasting, oxygen and temperature cycles play a significant role in its regulation. Chronic circadian misalignment can lead to numerous pathologies, including metabolic disorders, age-related diseases or cancer. Therefore, the use of resveratrol may be a valuable preventive and/or therapeutic strategy for these pathologies. This review summarizes studies that evaluated the modulatory effect of resveratrol on circadian oscillators by focusing on the potential and limitations of resveratrol in biological clock-related disorders.
Assessing the ‘Why’ in Volunteering for Refugees: Exploring Volunteer Motivations
Authors: Meijeren Maikel , Lubbers Marcel , Scheepers Peer
Published: May 2023

This article addresses what motivations volunteers have for volunteering for refugees and whether these motivations differ from or complement motivations to volunteer in general, such as included in the widely used measurement instrument, the Volunteer Function Inventory (VFI). We organized eight focus groups with volunteers for refugees (N = 44) and interviewed five involved coordinators, all working in one city in the Netherlands. Results show that humanitarian concerns and social justice were highly relevant for people’s motivations, next to volunteering to obtain or improve knowledge and skills. We find support for the earlier suggested extension of the VFI with the social justice motivation. Next, the current study expands existing analysis on volunteer motivations by identifying four areas that require further attention: (1) volunteers for refugees seek a meaningful role in life; (2) are motivated by the pragmatism of this volunteer work; (3) have emotional reasons; and (4) are motivated by media exposure.
Differences in Multi-Dimensional Well-Being Among Factory Workers: Evidence from Six Countries
Authors: Bialowolski Piotr , Lee Matthew T. , Weziak-Bialowolska Dorota , Chen Ying , Cowden Richard G. , McNeely Eileen , VanderWeele Tyler J.
Published: May 2023

This paper presents cross-cultural comparisons of well-being among factory workers, as measured by the six well-being domains of happiness and life satisfaction, physical and mental health, meaning and purpose, character and virtue, close social relationships, and financial and material stability. Relative ranks of well-being domains across examined groups of workers are also compared. Results are based on survey data from factory workers in Cambodia, China, Mexico, Poland, Sri Lanka, and the United States. Average well-being scores are higher among factory workers in Mexico, China, and Cambodia than in the U.S., Poland, and Sri Lanka across all domains except financial and material stability. Close social relationships were the highest ranked domain in Cambodia and China but ranked much lower (5th) in the U.S. Meaning and purpose, as well as character and virtue were highly ranked across the board. Strong social relationships seem to thrive in contexts where financial insecurity is high.
Indigenous trans-systemics: changing the volume on systems
Authors: McIntyre Don G. , Cloutis Geneva A. , McCarthy Dan
Published: May 2023

This paper emerged as a result of Anishinabe and non-Indigenous scholars discussing the basic principles behind systems thinking. By asking the question “what is a system?”, we uncovered that our very understanding of what makes a system was vastly different. As scholars working in cross-cultural and inter-cultural environments, these differing worldviews can create systemic challenges in unpacking complex problems. Trans-systemics offers language to unearth these assumptions by the recognition that the dominant, or “loudest”, systems are not always the most appropriate or equitable. It goes beyond critical systems thinking to identify that tackling complex problems requires the recognition that there are multiple, overlapping systems and worldviews at play. We identified three key takeaways from Indigenous trans-systemics for socio-ecological systems thinkers: (1) trans-systemics is a call to humility, asking us to critically examine our patterns of thought and behavior; (2) by exploring humility, trans-systemics allows us to move past the autopoiesis of Eurocentric systems thinking to consider interdependence; and (3) to utilize Indigenous trans-systemics, we need to fundamentally reconsider how we understand the systems around us and bring in outside tools and concepts to enact meaningful systems change.
Metformine in de praktijk: Een onderzoek naar metformine en intolerantie in de huisartsenpraktijk
Authors: Natan Oscar W.F. , Bouter K. Paul
Published: May 2023

Samenvatting

De afdeling Interne Geneeskunde van het Jeroen Bosch Ziekenhuis heeft begin 2022 een onderzoek gehouden onder kaderhuisartsen diabetes, huisartsen en praktijkondersteuners voor diabetes om een eerste, onderbouwd beeld te krijgen in welke mate de voorschriften en literatuur op het gebied van diabeteszorg enerzijds en de praktijk van alledag anderzijds overeenkomen. Daarnaast is gevraagd naar de bijwerkingen van metformine met directe afgifte (MGA) en hoe daarmee in de praktijk wordt omgegaan.

Uit dit verkennend onderzoek komt naar voren dat het overgrote deel van de respondenten lifestyleaanpassingen combineert met de inzet van metformine met directe afgifte (MDA). Volgens de literatuur heeft 41,4% na de start met metformine last van bijwerkingen.1 De ervaring leert dat na enkele weken de bijwerkingen van metformine afnemen. Volgens een onderzoek van Blond et al blijken de bijwerkingen op den duur af te nemen tot 26,34%.2 Volgens de resultaten van deze studie geeft 29% van de ondervraagden aan bijwerkingen te zien oplopend tot 50%. Als bijwerkingen zich voordoen, wordt in het overgrote deel van de gevallen de dosering verlaagd of wordt andere glucoseverlagende medicatie ingezet. Maar ook het tijdelijk of helemaal stoppen met de behandeling met metformine komt dikwijls naar voren. Opvallend weinig wordt er overgestapt op metformine MGA, terwijl 63% van de respondenten wel aangeeft dat het aantal klachten in het gunstigste geval vermindert.

Het is opvallend dat respondenten aangeven dat metformine MGA voordelen biedt ten behoeve van het voorkomen van bijwerkingen, omdat er in de literatuur verschillende uitkomsten te vinden zijn. Enkele onderzoeken zagen evenveel bijwerkingen tussen metformine MDA en MGA en enkele andere onderzoeken zagen minder bijwerkingen bij metformine MGA. Als we ermee rekening houden dat niet alle resultaten significant waren, blijkt er in de praktijk wel een trend te zien, waarbij metformine MGA een belangrijke rol kan spelen in het voorkomen van bijwerkingen. Of metformine MGA voordelen biedt bij het optitreren, het doen verminderen van bijwerkingen en/of leidt tot een hogere therapietrouw zal moeten blijken uit vervolgonderzoek. Hedendaags is het verschil in kosten tussen metformine MDA en MGA verwaarloosbaar en bij nieuwe positieve resultaten van metformine MGA zou een aanbeveling om te starten of te switchen naar metformine MGA in de richtlijnen gerechtvaardigd zijn.
The prevalence and outcomes of depression in older HIV-positive adults in Northern Tanzania: a longitudinal study
Authors: Dua Damneek , Stubbs Oliver , Urasa Sarah , Rogathe Jane , Duijinmaijer Ashanti , Howlett William , Dekker Marieke , Kisoli Aloyce , Mukaetova-Ladinska Elizabeta B. , Gray William K. , Lewis Thomas , Walker Richard W. , Dotchin Catherine L. , Lwezuala Bingileki , Makupa Philip C. , Paddick Stella Maria
Published: May 2023

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ2: 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p < 0.001), and increased functional impairment (p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target.
The role of Aboriginal education officers in the context of settler colonial schooling: challenges and possibilities
Authors: Armour Danielle , Miller Jodie
Published: May 2023

Educational policies indicate that the role of an Aboriginal Education Officer (AEO) is to build on contextual understanding and provide culturally appropriate support to assist Aboriginal and/or Torres Strait Islander students’ learning. There is little research exploring the role of the AEO from the perspective of Aboriginal peoples. The stories of four AEOs from New South Wales, Australia, will be shared through a narrative case study. This article will focus on AEOs’ experiences when they were initially employed in their schools. Findings suggest that the lack of clarity within the state-wide AEO statement of duties impacted the schools’ delegation to the AEOs. This, in turn impacted on the AEOs’ initial experience in the role and the inclusion of tasks that AEOs felt were outside of their expectations. Policy states that more Aboriginal educators are required in education systems but there are continual hurdles that AEOs face that prevent them from successfully performing their duties.
Fairness perceptions of educational inequality: the effects of self-interest and neoliberal orientations
Authors: Lee Jung-Sook , Stacey Meghan
Published: May 2023

The Australian education system features considerable socioeconomic inequality and is a frequent source of controversy in Australian public life. Yet meaningful reform to this system has proven elusive. In this article, we examine the public’s fairness perceptions of educational inequality based on parental financial capacity, using an online survey of adults (N = 1,999) from New South Wales, Australia. We asked about the fairness of inequality in school resources and education quality, and used a scenario in which students from high-income and low-income families had achievement gaps due to differences in educational experiences. Respondents had diverse perceptions about the fairness of educational inequality, but most perceived the scenario as unfair or very unfair. The partial proportional odds models showed that self-interest and neoliberal orientations predicted people’s fairness perceptions of educational inequality. The findings of this study have implications for achieving meaningful reform of the Australian education system that is in line with public opinion.
Navigating the paradox of excellence and equity in school leadership
Authors: Dadvand Babak
Published: May 2023

In this paper, I examine the tensions that a school principal experienced in reconciling performative priorities with equitable practices in a government secondary school in a low Socio-Economic Status suburb in Victoria, Australia. I use the notion of paradox to explore how the principal navigated contradictions and tensions. I aim to provide a more nuanced understanding of sense-making processes, agency, and capacity for action in the face of resource constraints, competing priorities and conflicting options in educational spaces. Drawing on Deleuze and Guattari’s notions of ‘striated spaces’ and ‘lines of flight’, I discuss how the principal worked simultaneously within and against inadequate resourcing and performativity pressures to cater for the more complex needs of a group of marginalised students in his school. I highlight the tensions that arose from this work. These tensions remained mostly unresolved, setting in motion an ongoing cycle of compliance, compromise, contradictions, and contestation. The findings show the complex interactions between material realities, punitive modes of accountability, self-discipline, and subjectivity. I conclude by discussing the need for an equity-informed policy agenda driven by a positive mode of accountability to enable equitable practices in school leadership and management.
Advances in KRAS mutation inhibition in metastatic colorectal cancer
Authors: Wu Chunhua , Li Wenfei , Chen Mifen , Zhang Qi , Xu Ting , Ma Yao , Liu Wanyi , Wang Zhenghang , Wang Xicheng , Li Jian , Bekaii-Saab Tanios , Shen Lin
Published: May 2023

KRAS is the most frequently mutated oncogene in human malignancies, observed in approximately two in five colorectal cancers (CRC). KRAS mutations were historically considered “undruggable” ten years ago and associated with resistance to EGFR targeted therapy. The success of finding allele-specific covalent KRASG12C inhibitors recently has made markedly breakthrough in KRAS targeted therapy, and has accelerated the discovery of agents targeting other KRAS mutants, such as G12D and G12V. Evidence in preclinical and clinical settings has proved excellent efficacy of several inhibitors in KRAS mutant CRC. Sotorasib and Adagrasib are currently changing the treatment paradigm for patients with metastatic CRC harboring KRASG12C mutation. The phenomenon that KRASG12C inhibition shows inferior efficacy in patients with CRC compared with non-small cell lung cancer has been observed in clinic due to drug resistance, and combination strategies to overcome the resistance are now being investigated in clinical trials. Here, we review the development of KRAS targeted treatment in CRC, mechanisms of resistance and potential combination strategies to improve efficacy.
Verifiable Autonomous Systems
Authors: Dennis Louise A. , Fisher Michael
Published: May 2023

How can we provide guarantees of behaviours for autonomous systems such as driverless cars? This tutorial text, for professionals, researchers and graduate students, explains how autonomous systems, from intelligent robots to driverless cars, can be programmed in ways that make them amenable to formal verification. The authors review specific definitions, applications and the unique future potential of autonomous systems, along with their impact on safer decisions and ethical behaviour. Topics discussed include the use of rational cognitive agent programming from the Beliefs-Desires-Intentions paradigm to control autonomous systems and the role model-checking in verifying the properties of this decision-making component. Several case studies concerning both the verification of autonomous systems and extensions to the framework beyond the model-checking of agent decision-makers are included, along with complete tutorials for the use of the freely-available verifiable cognitive agent toolkit Gwendolen, written in Java.
A data-driven method for automated data superposition with applications in soft matter science
Authors: Lennon Kyle R. , McKinley Gareth H. , Swan James W.
Published: May 2023

The superposition of data sets with internal parametric self-similarity is a longstanding and widespread technique for the analysis of many types of experimental data across the physical sciences. Typically, this superposition is performed manually, or recently through the application of one of a few automated algorithms. However, these methods are often heuristic in nature, are prone to user bias via manual data shifting or parameterization, and lack a native framework for handling uncertainty in both the data and the resulting model of the superposed data. In this work, we develop a data-driven, nonparametric method for superposing experimental data with arbitrary coordinate transformations, which employs Gaussian process regression to learn statistical models that describe the data, and then uses maximum a posteriori estimation to optimally superpose the data sets. This statistical framework is robust to experimental noise and automatically produces uncertainty estimates for the learned coordinate transformations. Moreover, it is distinguished from black-box machine learning in its interpretability—specifically, it produces a model that may itself be interrogated to gain insight into the system under study. We demonstrate these salient features of our method through its application to four representative data sets characterizing the mechanics of soft materials. In every case, our method replicates results obtained using other approaches, but with reduced bias and the addition of uncertainty estimates. This method enables a standardized, statistical treatment of self-similar data across many fields, producing interpretable data-driven models that may inform applications such as materials classification, design, and discovery.
Ministries matter: technocrats and regime loyalty under autocracy
Authors: York Erin
Published: May 2023

How do technocrat ministers affect governance under autocracy? Autocrats frequently appoint non-partisan actors with technical competencies to bureaucratic leadership roles. Though their competencies might predict positive performance in office, these ministers are also dependent on the regime for their position and should thus demonstrate loyalty to its interests. I test this in the context of horizontal accountability to the legislature, using data on more than 27,000 legislative requests submitted to ministries in Morocco. I use both exact matching and difference-in-differences analyses to show that technocrat ministers are more than 25 percentage points less likely to respond to legislative queries than partisan cabinet members. The results imply that outside (partisan) participation in government strengthens weak institutions of executive oversight. They also cast doubt on the presumption that technocrat participation in government is universally beneficial to governance.
Are Hobbesian States as Passionate as Hobbesian Individuals?
Authors: Rilla Jerónimo
Published: May 2023

This article deals with the possibility of ascribing passions to states in Thomas Hobbes's political theory. According to Hobbes, the condition of sovereign states vis-à-vis one another is comparable to that of individuals in the state of nature, namely, a state of war. Consequently, the three causes of war (competition, diffidence, and glory) identified in chapter 13 of Leviathan could also be relevant to interstate relations. Since these war triggers are mainly passions, one could presume that state action is motivated by passions as well. Some argue that it is just a figurative way of speaking. Others claim that the passions of war affect only sovereign rulers. I explore an alternative answer based on the ability of sovereigns to direct the preexisting passions of their people.
Truths from Morocco: Knowledge Production and Danish-Moroccan Encounters in the Eighteenth Century
Authors: Skålevåg Svein Atle
Published: May 2023

In the 1750s the Danish kingdom and the Moroccan Empire came into contact, and concluded a bilateral treaty. As part of the accord, a Danish chartered company was established. The company was short-lived and the “special relationship” between the two powers soon withered. A result of this episode was a handful of texts that sought to describe Morocco to a Danish audience—an adventure tale, a captive narrative, an orientalist chorography, and a biography of the emperor—which sought to produce truths about the Danish encounters with Morocco, but also truths about the place and the peoples of Morocco. The article discusses these texts, where they originated, to whom they circulated, and what they had to tell about Morocco.
Mapping interpretation by the International Criminal Court
Authors: Manley Stewart , Tehrani Pardis Moslemzadeh , Rasiah Rajah
Published: May 2023

This article is one of very few attempts to empirically measure legal interpretation. It maps the application of eleven interpretation elements (good faith, ordinary meaning, object and purpose, etc.) in Articles 31 and 32 of the Vienna Convention on the Law of Treaties (VCLT) across ten International Criminal Court case studies. The elements were coded for identity and sequence of element, and amount of text used in applying each element. The mapping and analysis reveal, among other things, that the application of the VCLT across cases is markedly inconsistent and, in some instances, opaque and arguably unjustifiable. The results suggest, at least based on this small sample, that the ICC’s current practice of applying the accommodating, flexible methodology of the VCLT may be inconsistent with the requirement of strict construction in Article 22 of the Rome Statute, and that even when strict construction does not technically apply, a more systematic, transparent, and robust approach should nevertheless still be followed.