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Awkward postures are a significant contributor to work-related musculoskeletal disorders (WRMSDs), which represent great social and economic burdens. Various posture assessment tools assess WRMSD risk but fall short in providing an elucidating risk breakdown to expedite the typical time-consuming ergonomic assessments. Quantifying, automating, but also complementing posture risk assessment become crucial. Thus, we developed a framework for a holistic posture assessment, able to, through inertial data, quantify the ergonomic risk and also qualitatively identify the posture leading to it, using Deep Learning. This innovatively enabled the generation of a report in a graphical user interface (GUI), where the ergonomic score is intuitively associated with the postures adopted, empowering workers to learn which are the riskiest postures, and helping ergonomists and managers to redesign critical work tasks. The continuous posture assessment also considered the previous postures’ impact on joint stress through a kinematic wear model. As use case, thirteen subjects replicated harvesting and bricklaying, work tasks of the two activity sectors most affected by WRMSDs, agriculture and construction, and a posture assessment was conducted. Three ergonomists evaluated this report, considering it very useful in improving ergonomic assessments’ effectiveness, expeditiousness, and ease of use, with the information easily understandable and reachable.

This article offers a critical review of the post-pandemic inflation debate. The first section organizes the debate by categorizing the arguments into two broad perspectives: the neoclassical view and the critical political economy view, along with several subcategories. This classification is guided by the positions that participants in the debate took regarding the origins and propagation mechanisms of inflation, as well as the economic policy solutions proposed to address the current inflationary period. The second section highlights that the dominance of contractionary monetary policy as the primary response to contemporary inflation rests on weak foundations, with its theoretical and empirical justifications having been consistently and convincingly challenged by critical political economy circles over the past decades.

IntroductionAdolescence and youth are periods of significant maturational changes, which seem to involve greater susceptibility to disruptive events in the brain, such as binge drinking (BD). This pattern—characterised by repeated episodes of alcohol intoxication—is of particular concern, as it has been associated with significant alterations in the developing brain. Recent evidence indicates that alcohol may also induce changes in gut microbiota composition and that such disturbances can lead to impairments in both brain function and behaviour. Moreover, there is evidence suggesting that microbiota-targeted interventions (psychobiotics) may help mitigate alcohol-induced damage in individuals with chronic alcohol use, positively influencing cognitive and brain functioning. However, the triadic relationship between BD, gut microbiota and brain structure/function, as well as the therapeutic potential of gut microbiota-targeted interventions in young binge drinkers, remains largely unexplored.Methods and analysisThis double-blind, parallel, randomised controlled study aims to evaluate whether a BD pattern disrupts gut microbiota diversity in young college students (primary outcome). Additionally, it seeks to determine whether alcohol-induced alterations in the microbial composition and function are associated with immunological, cognitive, neurostructural and neurofunctional impairments (secondary outcomes). A total of 82 college students (36 non/low drinkers and 46 binge drinkers (BDs)), matched for age and sex, will be recruited from the University of Minho (Portugal). During the pre-intervention phase, all participants will undergo a comprehensive assessment protocol, including gut microbiota profiling, measurement of inflammatory markers, neuropsychological testing and structural and functional MRI. BDs will then be randomly assigned to a 6-week intervention with either a prebiotic (inulin) or a placebo (maltodextrin). Post-intervention assessment will mirror the baseline protocol, and craving and alcohol use will be monitored for 3 months.Ethics and disseminationThe present protocol was approved by the Ethics Committee for Social and Human Sciences of the University of Minho (CEICSH 078/2022), ensuring compliance with national and international ethical guidelines, including the Declaration of Helsinki. Participation is voluntary and preceded by informed consent, with confidentiality and data processing safeguarded in accordance with the General Data Protection Regulation. All procedures are safe and non-invasive, and the prebiotics used are recognised as food ingredients in Europe, hold Generally Recognized as Safe status in the USA and are classified as dietary fibres by the Food and Drug Administration. Findings will be disseminated in national and international scientific forums, with preference for publication in open-access, peer-reviewed journals.Trial registration numberNCT05946083

Drought and wetness events were studied in the Northeast Algeria with SPI and RDI. The study area includes a variety of climatic conditions, ranging from humid in the North, close to the Mediterranean Sea, to arid in the South, near the Sahara Desert. SPI only uses precipitation data while RDI uses a ratio between precipitation and potential evapotranspiration (PET). The latter was computed with the Thornthwaite equation, thus using temperature data only. Monthly precipitation data were obtained from 123 rainfall stations and monthly temperature data were obtained from CFSR reanalysis gridded temperature data. Both data sets cover the period 1979–80 to 2013–14. Using ordinary kriging, the gridded temperature data was interpolated to all the locations having precipitation data, thus providing to compute SPI and RDI with the same observed rainfall data for the 3-, 6- and 12-month time scales. SPI and RDI were therefore compared at station level and results and have shown that both indices revealed more sensitive to drought when applied in the semi-arid and arid zones. Differently, more wetness events were detected by RDI in the more humid locations. Comparing both indices, they show a coherent and similar behavior, however RDI shows smaller differences among climate zones and time-scales, which is an advantage relative to the SPI and is likely due to including PET in RDI.

The spatial and temporal variability of droughts were studied for the Northeast Algeria using SPI and RDI computed with monthly precipitation data from 123 rainfall stations and CFSR reanalysis monthly temperature data covering the period 1979–80 to 2013–14. The gridded temperature data was interpolated to all the locations having precipitation data, thus providing to compute SPI and RDI with the time scales of 3-, 6- and 12-month with the same observed rainfall data. Spatial and temporal patterns of droughts were obtained using Principal Component Analysis in S-Mode with Varimax rotation applied to both SPI and RDI. For all time scales of both indices, two principal components were retained identifying two sub-regions that are similar and coherent for all SPI and RDI time scales. Both components explained more than 70% and 74% of drought spatial variability of SPI and RDI, respectively. The identified sub-regions are similar and coherent for all SPI and RDI time scales. The Modified Mann-Kendall test was used to assess trends of the RPC scores, which have shown non-significant trends for decreasing drought occurrence and severity in both identified drought sub-regions and all time scales. Both indices have shown a coherent and similar behavior, however with RDI likely showing to identify more severe and moderate droughts in the southern and more arid sub-region which may be due to its ability to consider influences of global warming. Results for RDI are quite uniform relative to time scales and show smaller differences among the various climates when compared with SPI. Further assessments covering the NW and NE of Algeria using longer time series should be performed to better understand the behavior of both indices.

Muscle architecture parameters performed using ultrasound serve as an aid to monitor muscle changes derived from diseases, however there are no studies that determine the reliability and applicability of this evaluation in individuals with type 2 diabetes (DM2). Three raters captured three images of measurements of thickness of the rectus femoris (RF), vastus intermedius and anterior quadriceps, RF muscle cross-sectional area, RF pennation angle in 17 individuals with DM2 above 50 and sedentary. Intra and inter-raters analysis showed reliability from high to very high for the three raters (ICC> 0.87), except for the RF pennation angle with moderate to low intra-raters (ICC = 0.58, 0.48, 0.51), and high inter-rater reliability (ICC = 0.70). Ultrasound measurements of quadriceps muscles showed high to very high intra and inter-raters reliability, thus allowing its use to monitor muscle changes provoked by diabetes or interventions in individuals with DM2.

Bacteria that reside in the gastrointestinal tract of healthy humans are essential for our health, sustenance and well-being. About 50–60% of those bacteria have the ability to produce resilient spores that are important for the life cycle in the gut and for host-to-host transmission. A genomic signature for sporulation in the human intestine was recently described, which spans both commensals and pathogens such as Clostridioides difficile and contains several genes of unknown function. We report on the characterization of a signature gene, CD25890 , which, as we show is involved in the control of sporulation initiation in C. difficile under certain nutritional conditions. Spo0A is the main regulatory protein controlling entry into sporulation and we show that an in-frame deletion of CD25890 results in increased expression of spo0A per cell and increased sporulation. The effect of CD25890 on spo0A is likely indirect and mediated through repression of the sinRR ´ operon. Deletion of the CD25890 gene, however, does not alter the expression of the genes coding for the cytotoxins or the genes involved in biofilm formation. Our results suggest that CD25890 acts to modulate sporulation in response to the nutrients present in the environment.

The characterization of historical mine tailings provides important information for land-management decisions, in particular when considering potential reprocessing activities or the development of an environmental protection program. In addition, outcomes from such characterization may define the scope for a more detailed investigation. The present work describes the characterization of the waste material from the Cabeço do Pião tailings impoundment performed within the project ReMinE: Improve Resource Efficiency and Minimize Environmental Footprint. The purpose of the work was to investigate alternative mine waste management options such as the extraction of valuable resources from an environmental liability. The study involved the collection of 41 samples at different locations at two different depths, physical and chemical characterization of the wastes, natural leaching tests, and potential for acid generation. The results showed that, apart from the potential instability of the dyke (with an average slope of 35°), the drained solutions flowing by percolation contain very small particles with high arsenic contents that are being incorporated into the river sediments. In addition, these very fine-grained materials are available for the transport by the wind creating secondary sources of environmental contamination. This data is fundamental for economic and environmental assessment of the two main alternatives, reprocessing or removal.

Sulfur fluoride exchange (SuFEx) has emerged as the new generation of click chemistry. We report here a SuFEx-enabled, agnostic approach for the discovery and optimization of covalent inhibitors of human neutrophil elastase (hNE). Evaluation of our ever-growing collection of SuFExable compounds toward various biological assays unexpectedly revealed a selective and covalent hNE inhibitor: benzene-1,2-disulfonyl fluoride. Synthetic derivatization of the initial hit led to a more potent agent, 2-(fluorosulfonyl)phenyl fluorosulfate with IC50 0.24 μM and greater than 833-fold selectivity over the homologous neutrophil serine protease, cathepsin G. The optimized, yet simple benzenoid probe only modified active hNE and not its denatured form.

Antibody–drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the payload. By combining the specificity of mABs with the high potency of the payloads, ADCs constitute a smart drug delivery system with improved therapeutic index. After recognition and binding of the mAB to its target surface antigen, ADCs are internalized by endocytosis by the tumor cell, releasing the payloads into the cytoplasm, where they exert their cytotoxic activity, eventually leading to cell death. The composition of some of the new ADCs confers additional functional properties that allow expanding their activity to neighboring cells not expressing the target antigen, constituting a valuable strategy to overcome tumor heterogeneity. Some of these ‘off-target effects’, such as the bystander effect, are possibly the mechanism underlying the antitumor activity demonstrated in patients with low expression of the target antigens, which represents an important paradigm shift in anticancer targeted therapy. Three ADCs are currently approved for the treatment of breast cancer (BC); two anti-HER2 (human epidermal growth factor receptor 2) ADCs (trastuzumab emtansine and trastuzumab deruxtecan); and one Trop-2-targeted ADC (sacituzumab govitecan). Based on the unprecedented efficacy data demonstrated by these agents, ADCs have been incorporated as part of standard regimens for all subtypes of advanced BC, as well as for high-risk early HER2-positive BC. Despite the remarkable advances, several hurdles still remain to overcome, including the development of reliable biomarkers for patient selection, prevention, and management of potentially severe toxicities, ADC resistance mechanisms, post-ADC resistance patterns, and optimal treatment sequencing and combinations. In this review, we will summarize the currently available evidence related to the use of these agents, as well as explore the current landscape of ADC development for BC treatment.