Miracle-dz/UniFAR-FTUs huggingface dataset:
A heterodimer of α and β hemoglobin chains functions as an innate anticancer agent

Metastatic (as well as tumor) microenvironments contain both cancer‐promoting and cancer‐restraining factors. The balance between these opposing forces determines the fate of cancer cells that disseminate to secondary organ sites. In search for microenvironmental drivers or inhibitors of metastasis, we identified, in a previous study, the beta subunit of hemoglobin (HBB) as a lung‐derived antimetastatic factor. In the present study, exploring mechanisms regulating melanoma brain metastasis, we discovered that brain‐derived factors restrain proliferation and induce apoptosis and necrosis of brain‐metastasizing melanoma cells. Employing various purification procedures, we identified a heterodimer composed of hemoglobin alpha and beta chains that perform these antimetastatic functions. Neither the alpha nor the beta subunit alone was inhibitory. An alpha/beta chain dimer chemically purified from human hemoglobin inhibited the cell viability of primary melanomas, melanoma brain metastasis (MBM), and breast cancer cell lines. The dimer‐induced DNA damage, cell cycle arrest at the SubG1 phase, apoptosis, and significant necrosis in four MBM cell lines. Proteomic analysis of dimer‐treated MBM cells revealed that the dimer downregulates the expression of BRD4, GAB2, and IRS2 proteins, playing crucial roles in cancer cell sustainability and progression. Thus, we hypothesize that the hemoglobin dimer functions as a resistance factor against brain‐metastasizing cancer cells.
What is the evidence for the effect of physical exercise on bone health in menopausal women? An umbrella systematic review

Abstract This study aimed to analyze the effects of physical exercise (PE) on bone health in menopausal women through an umbrella review and to assess the quality of systematic reviews (SRs) and meta-analyses (MAs) included. The review was registered in PROSPERO (CRD42020208130) and the Rayyan application was used. The methodological quality of the included studies was evaluated by A MeaSurement Tool to Assess Systematic Reviews (AMSTAR), and Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to assess the level of evidence of the results. The results showed that low-intensity jumping exercises with longer sessions proved to be efficient in the hip segment. Swimming requires further investigation, as it showed high heterogeneity. Aerobic and resistance exercises showed inconsistent results, requiring further studies with these modalities of PE. Concurrent training showed improvements in the lumbar spine, femoral neck, Ward’s triangle and trochanter. Finally, combined resistance exercises are effective in preserving bone mineral density (BMD) of the femoral neck and lumbar spine in postmenopausal women. In conclusion, jumping exercises were efficient in the hip, while aerobic and resistance exercises are still inconsistent. Concurrent training showed improvements in BMD of the lumbar spine, femoral neck, Ward’s triangle and trochanter. Finally, combined resistance protocols are effective in preserving BMD of the femoral neck and lumbar spine in postmenopausal women.
The impact of access to electricity on mental health in conflict-affected territories: An exploratory study in Gaza

Background: Access to affordable and clean energy is an essential component of the Sustainable Development Goals and a determinant of physical and mental health. However, the occupied Palestinian territory, the Gaza Strip, has experienced prolonged issues with electricity, water and gas supplies. This has significantly impacted on daily life and the area is on the verge of disaster. This research focused on the mental health effects of the lack of electricity in Gaza which have not been previously documented. Methods: A cross-sectional analytic approach was adopted. A survey was administrated face-to-face with respondents from 350 participating households. Inferential statistical analysis was used to examine the relationship between the domains of anxiety, depression, wellbeing and electricity supply factors. A multiple linear regression model was also utilised. Results: There is a highly statistically significant link between continuity of electricity and level of anxiety (p < .001). The same effect was reported in the level of depression, and a higher level was observed among residents with an intermittent or disrupted electricity supply, with a statistically significant link between the level of depression and continuity of electricity. Conclusion: Electricity issues, especially when combined with other stressors associated with living in Gaza, lead to serious mental health concerns. Urgent attention must be given to developing sustainable, reliable and affordable energy supplies for short- and long-term health and community development.
Route sequence knowledge supports the formation of cognitive maps

In this study, we examined the extent to which knowledge about the sequence of places encountered during route learning supports the formation of a metric cognitive map. In a between subjects design, participants learned a route until they could navigate it independently without error whilst also learning information about either the identity of places along the route (Recognition Learning condition) or the sequence of places along the route (Sequence Learning condition). In a follow‐up Reconstruction of Order Task, we confirmed that participants in the Sequence Learning condition had more accurate route sequence knowledge than those in the Recognition Learning condition, despite requiring the same overall number of trials to learn the route. Participants then completed a Pointing Task to assess the quality of their cognitive map of the environment. Both groups performed above chance level, showing incidental encoding of metric information, but the Sequence Learning group produced significantly lower pointing errors than the Recognition Learning group. Further, we found that route distance between pairs of places was a strong predictor of pointing error in both groups, whilst Euclidean distance between places was a significant, but weak, predictor only for the Sequence Learning condition. The results of this study demonstrate that discrete route sequence knowledge directly supports the formation of metric cognitive maps. We consider how the results are best explained by interactions between striatal route representations and hippocampal metric representations, centered around the sequence of places acting as a scaffold for the encoding of metric information.
An optimized grid data set of mean monthly and annual runoff for Switzerland: coupling modelled data with robust information derived from observations.

Mean monthly and annual runoffs are the classical parameters for quantifying and describing the discharge regime of a river basin. A new grid-based data set for the whole of Switzerland at 500 x 500 m 2 resolution has been processed. Two different information sources, each bringing in its respective strengths and limitations have been combined: (1) the output of a "modelling-experiment" for Switzerland with the semi-distributed hydrological model PREVAH; (2) a data set of high quality regionalized runoff data for medium-scale catchments. Taking the second data set as quantitatively reliable, the original modelled raster data have been adjusted in such a way that they fulfil the balance equation for the single medium-scale catchments. The validations of both data sets show that the combined data set represents a significant improvement with respect to the original data set. The data can be adopted by practitioners for estimating the seasonal discharge pattern for gauged and ungauged mountainous basins with areas ranging between 10 and 1000 km 2 .
Multi-species state-space modelling of the hen harrier (Circus cyaneus) and red grouse (Lagopus lagopus scoticus) in Scotland

State-space modelling is a powerful tool to study ecological systems. The direct inclusion of uncertainty, unification of models and data, and ability to model unobserved, hidden states increases our knowledge about the environment and provides new ecological insights. I extend the state-space framework to create multi-species models, showing that the ability to model ecosystem interactions is limited only by data availability. State-space models are fit using both Bayesian and Frequentist methods, making them independent of a statistical school of thought. Bayesian approaches can have the advantage in their ability to account for missing data and fit hierarchical structures and models with many parameters to limited data; often the case in ecological studies. I have taken a Bayesian model fitting approach in this thesis. The predator-prey interactions between the hen harrier (Circus cyaneus) and red grouse (Lagopus lagopus scoticus) are used to demonstrate state-space modelling’s capabilities. The harrier data are believed to be known without error, while missing data make the cyclic dynamics of the grouse harder to model. The grouse-harrier interactions are modelled in a multi-species state-space model, rather than including one species as a covariate in the other’s model. Finally, models are included for the harriers’ alternate prey. The singleand multi-species state-space models for the predator-prey interactions provide insight into the species’ management. The models investigate aspects of the species’ behaviour, from the mechanisms behind grouse cycles to what motivates harrier immigration. The inferences drawn from these models are applicable to management, suggesting actions to halt grouse cycles or mitigate the grouse-harrier conflict. Overall, the multi-species models suggest that two popular ideas for grouse-harrier management, diversionary feeding and habitat manipulation to reduce alternate prey densities, will not have the desired effect, and in the case of reducing prey densities, may even increase the harriers’ impact on grouse chicks.
Common and disorder-specific cortical thickness alterations in internalizing, externalizing and thought disorders during early adolescence: an Adolescent Brain and Cognitive Development study

Background: A growing body of neuroimaging studies has reported common neural abnormalities among mental disorders in adults. However, it is unclear whether the distinct disorder-specific mechanisms operate during adolescence despite the overlap among disorders. Methods: We studied a large cohort of more than 11 000 preadolescent (age 9–10 yr) children from the Adolescent Brain and Cognitive Development cohort. We adopted a regrouping approach to compare cortical thickness (CT) alterations and longitudinal changes between healthy controls (n = 4041) and externalizing (n = 1182), internalizing (n = 1959) and thought disorder (n = 347) groups. Genome-wide association study (GWAS) was performed on regional CT across 4468 unrelated European youth. Results: Youth with externalizing or internalizing disorders exhibited increased regional CT compared with controls. Externalizing (p = 8 × 10−4, Cohen d = 0.10) and internalizing disorders (p = 2 × 10−3, Cohen d = 0.08) shared thicker CT in the left pars opercularis. The somatosensory and the primary auditory cortex were uniquely affected in externalizing disorders, whereas the primary motor cortex and higher-order visual association areas were uniquely affected in internalizing disorders. Only youth with externalizing disorders showed decelerated cortical thinning from age 10–12 years. The GWAS found 59 genome-wide significant associated genetic variants across these regions. Cortical thickness in common regions was associated with glutamatergic neurons, while internalizing-specific regional CT was associated with astrocytes, oligodendrocyte progenitor cells and GABAergic neurons. Limitations: The sample size of the GWAS was relatively small. Conclusion: Our study provides strong evidence for the presence of specificity in CT, developmental trajectories and underlying genetic underpinnings among externalizing and internalizing disorders during early adolescence. Our results support the neurobiological validity of the regrouping approach that could supplement the use of a dimensional approach in future clinical practice.
Human iPSC‐derived endothelial cells promote CNS remyelination via BDNF and mTORC1 pathway

Damage of myelin is a component of many diseases in the central nervous system (CNS). The activation and maturation of the quiescent oligodendrocyte progenitor cells (OPCs) are the crucial cellular processes for CNS remyelination, which is influenced by neuroinflammation in the lesion microenvironment. Endothelial cells derived from human induced pluripotent stem cells (hiPSC‐ECs) have shown promise in restoring function in various preclinical animal models. Here we ask whether and whether transplantation of hiPSC‐ECs could benefit remyelination in a mouse model of CNS demyelination. Our results show that in vitro, hiPSC‐ECs increase OPC proliferation, migration and differentiation via secreted soluble factors including brain‐derived neurotrophic factor (BDNF). hiPSC‐ECs also promote the survival of oligodendrocyte lineage cells in vitro and in vivo. Transplantation of hiPSC‐ECs into a toxin‐induced demyelination lesion in mouse corpus callosum (CC) leads to increased density of oligodendrocyte lineage cells and level of myelin in demyelinated area, correlated with a decreased neuroinflammation and an increased proportion of pro‐regenerative M2 phenotype in microglia/macrophages. The hiPSC‐EC‐exposed oligodendrocyte lineage cells showed significant increase in the level of phosphorylated S6 ribosomal protein (pS6) both in vitro and in vivo, indicating an involvement of mTORC1 pathway. These results suggest that hiPSC‐ECs may benefit myelin protection and regeneration which providing a potential source of cell therapy for a wide range of diseases and injuries associated with myelin damage.
Variable selection using inverse probability of censoring weighting

In this article, we propose two variable selection methods for adjusting the censoring information for survival times, such as the restricted mean survival time. To adjust for the influence of censoring, we consider an inverse probability of censoring weighted for subjects with events. We derive a least absolute shrinkage and selection operator (lasso)-type variable selection method, which considers an inverse weighting for of the squared losses, and an information criterion-type variable selection method, which applies an inverse weighting of the survival probability to the power of each density function in the likelihood function. We prove the consistency of the inverse probability of censoring weighted lasso estimator and the maximum inverse probability of censoring weighted likelihood estimator. The performance of the inverse probability of censoring weighted lasso and inverse probability of censoring weighted information criterion are evaluated via a simulation study with six scenarios, and then their variable selection ability is demonstrated using data from two clinical studies. The results confirm that inverse probability of censoring weighted lasso and the inverse probability of censoring weighted likelihood function produce good estimation accuracy and consistent variable selection. We conclude that our two proposed methods are useful variable selection tools for adjusting the censoring information for survival time analyses.
The Influence of Compensatory Pelvic Tilt on Patient‐reported Outcome Measurements in FAI Patients Who Received Arthroscopic Treatment

Pelvic compensation is common in femoroacetabular impingement (FAI) patients to reduce symptoms and increase range of motion. However, little attention was given to the postoperative clinical effect of pelvic compensation. Therefore, this study aims to compare the outcomes between pelvic compensation and normal pelvic position in femoroacetabular impingement (FAI) patients after hip arthroscopy.
The effect of parenteral vitamin B12 on the growth rate of dairy calves over the summer and autumn on seven farms from the Central Plateau, New Zealand

ABSTRACT Aims To investigate the effect of parenteral vitamin B12 supplementation on the growth rate of dairy heifer calves over the summer and autumn on seven farms from the Central Plateau of New Zealand, an area historically associated with low cobalt levels in grazing pasture. Methods This was a controlled clinical trial conducted on a convenience sample of seven farms with young female calves randomly assigned to three vitamin B12 treatment groups and followed through a grazing season. Two treatment groups received either monthly SC injections of a short-acting (SA) B12 formulation or 3-monthly injections of a long-acting (LA) B12 formulation and the third group received no treatment (NT). No additional parenteral vitamin B12 was given; however, all calves received additional cobalt (0.04–0.4 mg Co/kg liveweight) in the mineralised anthelmintic drenches given orally every month. Liveweight was recorded in December/January and at the end of the trial in May/June/July depending on farm. Pasture cobalt concentrations (mg/kg DM) were measured every month using 500-g herbage samples from 100-m transects in the area about to be grazed by the trial groups. Results There was evidence for a difference in growth rate between groups with mean final weight of 228 (95% CI = 212–243) kg for the LA groups, 224 (95% CI = 209–239) kg for the SA groups and 226 (95% CI = 211–241) kg for the NT groups respectively, (global p-value = 0.014). Calves given SA vitamin B12 were 3.77 (95% CI = 0.71–6.82) kg lighter than calves given LA vitamin B12 (p = 0.011). There was no evidence for a change in pasture cobalt concentrations (p = 0.32). Conclusions and clinical relevance The results of this trial raise the question as to whether the routine use of vitamin B12 supplementation in young cattle from areas traditionally thought to be cobalt deficient is necessary, and further raise the possibility that vitamin B12 supplementation by repeated injection of SA products may negatively impact growth rates.
Addressing the unique challenges in studies of long‐term medication use and dementia risk

<jats:p>This editorial comments on the article by <jats:ext-link xmlns:xlink="http://www.w3. org/1999/xlink" xlink:href="https://doi.org/10.1111/jgs.18397">Wu et al</jats:ext-link>. </jats:p>
Identification of microbial markers associated with lung cancer based on multi‐cohort 16 s rRNA analyses: A systematic review and meta‐analysis

The relationship between commensal microbiota and lung cancer (LC) has been studied extensively. However, developing replicable microbiological markers for early LC diagnosis across multiple populations has remained challenging. Current studies are limited to a single region, single LC subtype, and small sample size. Therefore, we aimed to perform the first large‐scale meta‐analysis for identifying micro biomarkers for LC screening by integrating gut and respiratory samples from multiple studies and building a machine‐learning classifier.
Adaptation and validation of the PAC-19QoL-specific quality of life questionnaire for the Spanish population with long COVID

Abstract Introduction The post-acute (long) COVID-19 Quality of Life instrument is the only specific instrument designed to assess the quality of life in long COVID patients. The present study aims to make a transcultural adaptation and validation into Spanish of the disease-specific (long COVID) quality of life instrument, post-acute (long) COVID-19 Quality of Life, to have a tool for objective measurement of quality of life in this population. Methods A descriptive cross-sectional study was divided into two phases. In phase one, the translation and cultural adaptation of the questionnaire was performed, while in phase two, the questionnaire was validated. The Spanish version of the questionnaire was used with a sample of 206 people, 40 males (19.4%) and 166 females (80.6%), with an age range between 21 and 70 years old. Participants completed the questionnaire through an online platform. Internal consistency, construct validity, convergent validity, test-retest reliability, and ceiling and floor effects of the Spanish version were analyzed. Results The Spanish version of the post-acute (long) COVID-19 Quality of Life instrument showed high internal consistency, with Cronbach's alpha= 0.922 and an intraclass correlation coefficient of 0.936. Mean scores obtained in the PAC-19QoL and SF-12 questionnaires showed that those who had a worse quality of life in the SF-12 tool also a had worse quality of life in the PAC-19QoL tool. Conclusions This study shows that the Spanish version of the post-acute (long) COVID-19 Quality of Life instrument is an appropriate and valid tool for assessing the quality of life of long COVID patients.
Measuring the reliability of binocular rivalry

Binocular rivalry is a widely used tool in sensory and cognitive neuroscience to investigate different aspects of vision and cognition. The dynamics of binocular rivalry (e.g., duration of perceptual dominance phases and mixed percept proportions) differ across individuals; based on rivalry dynamics, it is also possible to calculate an index of ocular dominance (by comparing the perceptual dominance of the images in the two eyes). In this study, we investigated the reliability of binocular rivalry dynamics using different methods for dichoptic stimulation and different rivalry stimuli. For the three main indices we defined (ocular dominance, phase durations and mixed percept proportions), we found a high test–retest reliability across sessions. Moreover, the test–retest reliability of the ocular dominance index was predictable from its internal consistency, supporting its stability over time. Phase durations and mixed percept proportions, in contrast, had worse test–retest reliability than expected based on internal consistency, indicating that these parameters are susceptible to state-dependent changes. Our results support the use of the ocular dominance index and binocular rivalry in the measurement of sensory eye dominance and its plasticity, but advise caution when investigating the association between phase durations or mixed percepts and stable characteristics like psychological traits or disorders.