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Hyperammonaemia syndrome secondary to

Iron deficiency and the more severe sequela, iron deficiency anemia, are public health problems associated with morbidity and mortality, particularly among pregnant women and younger children. The 1998 Centers for Disease Control and Prevention recommendations for prevention and control of iron deficiency in the United States is old and does not reflect recent evidence but is a foundational reference for many federal, clinical, and program guidelines.Surveillance data for iron deficiency are sparse at all levels, with critical gaps for pregnant women and younger children. Anemia, iron deficiency, and iron deficiency anemia are often conflated but should not be. Clinical guidelines for anemia, iron deficiency, and iron deficiency anemia give inconsistent recommendations, causing nonsystematic assessment of iron deficiency. Screening for iron deficiency typically relies on identifying anemia, despite anemia’s low sensitivity for iron deficiency. In the National Health and Nutrition Examination Survey, more than 70% of iron deficiency is missed among pregnant women and children by relying on hemoglobin for iron deficiency screening.To improve assessment and diagnosis and strengthen surveillance, better and more complete data and updated foundational guidance on iron deficiency and anemia are needed that consider new evidence for measuring and interpreting laboratory results. (Am J Public Health. 2022;112(S8):S826–S835. https://doi.org/10.2105/AJPH.2022.306998 )

COVID-19 has been associated with a range of illness severity-from minimal symptoms to life-threatening multisystem organ failure. The severe forms of COVID-19 appear to be associated with an angiocentric or vascular phase of the disease. In studying autopsy patients succumbing to COVID-19, we found alveolar capillary microthrombi were 9 times more common in COVID-19 than in comparable patients with influenza. Corrosion casting of the COVID-19 microcirculation has revealed microvascular distortion, enhanced bronchial circulation, and striking increases in intussusceptive angiogenesis. In patients with severe COVID-19, endothelial cells commonly demonstrate significant ultrastructural injury. High-resolution imaging suggests that microcirculation perturbations are linked to ischemic changes in microanatomic compartments of the lung (secondary lobules). NanoString profiling of these regions has confirmed a transcriptional signature compatible with microischemia. We conclude that irreversible tissue ischemia provides an explanation for the cystic and fibrotic changes associated with long-haul COVID-19 symptoms.

Mast cells are critical innate immune effectors located throughout the body that are crucial for host defense mechanisms via orchestrating immune responses to a variety of host and environmental stimuli necessary for survival. The role of mast cells in brain development and behavior, meningeal function, and stress-related disorders has also been increasingly recognized. While critical for survival and development, excessive mast cell activation has been linked with an increasing number of inflammatory, stress-associated, and neuroimmune disorders including allergy/anaphylaxis, autoimmune diseases, migraine headache, and chronic pain disorders. Further, a strong sex bias exists for mast cell-associated diseases with females often at increased risk. Here we review sex differences in human mast cell-associated diseases and animal models, and the underlying biological mechanisms driving these sex differences, which include adult gonadal sex hormones as well the emerging organizational role of perinatal gonadal hormones on mast cell activity and development.

Spinal solitary fibrous tumour (SFT) is an uncommon tumour with few cases reported in the literature. It rarely originates at the craniocervical junction. To our knowledge, only eight cases of spinal SFT located at the craniocervical junction have been reported in the literature. We presented a patient with a craniocervical junction SFT and discussed its clinical presentation, radiological features, pathology, management and outcome. This was the first patient reported in the literature with a recurrent craniocervical junction SFT treated with Gamma Knife radiosurgery. The treatment reduced the tumour volume by more than 85% within 12 months.

Oncocytic adrenocortical neoplasms are a rare histopathological subtype of adrenal tumours which are usually benign and, if malignant, are less likely to metastasise. We report a case of a non-functioning oncocytic adrenocortical tumour, identified incidentally in a middle-aged woman. It was initially reported as a left-sided 3.5×3.4×5.6 cm adrenal adenoma. It however increased in size to 5.4×4.0×4.3 cm on follow-up scans. Subsequent review of the scans revealed an indeterminate lesion with a precontrast density of 30 Hounsfield units, an absolute washout of 42.6% and a relative washout of 28.6%. As a result, laparoscopic left adrenalectomy was performed. Histology confirmed oncocytic adrenocortical carcinoma when using the Lin-Weiss-Bisceglia system, though it was deemed benign when using the Helsinki scoring system. There has been no evidence of recurrence to date. This case highlights the potential pitfalls in the diagnosis of oncocytic neoplasms and the increased specificity of the Helsinki score in assessing metastatic potential.

Lead exposure that occurs from contamination inadvertently brought home from a workplace is known as take-home exposure. Take-home exposures are a public health hazard that adversely affects health equity for families and communities. This article describes coordinated action by agencies in Minnesota to curb lead exposure among children of workers at a facility that produces fishing sinkers and battery terminals. (Am J Public Health. 2022;112(S7):S655–S657. https://doi.org/10.2105/AJPH.2022.306982 )

Objectives. To evaluate lead levels in tap water at licensed North Carolina child care facilities. Methods. Between July 2020 and October 2021, we enrolled 4005 facilities in a grant-funded, participatory science testing program. We identified risk factors associated with elevated first-draw lead levels using multiple logistic regression analysis. Results. By sample (n = 22 943), 3% of tap water sources exceeded the 10 parts per billion (ppb) North Carolina hazard level, whereas 25% of tap water sources exceeded 1 ppb, the American Academy of Pediatrics’ reference level. By facility, at least 1 tap water source exceeded 1 ppb and 10 ppb at 56% and 12% of facilities, respectively. Well water reliance was the largest risk factor, followed by participation in Head Start programs and building age. We observed large variability between tap water sources within the same facility. Conclusions. Tap water in child care facilities is a potential lead exposure source for children. Given variability among tap water sources, it is imperative to test every source used for drinking and cooking so appropriate action can be taken to protect children’s health. (Am J Public Health. 2022;112(S7):S695–S705. https://doi.org/10.2105/AJPH.2022.307003 )

Fluvial point bar deposits are described from the ca. 1 Ga Diabaig Formation, representing some of the most compelling architectural evidence of planform sinuosity recognized in pre-vegetation sedimentary strata to date. The stratigraphic architecture of the deposits indicates different planform transformations in response to meander-bend expansion and downstream migration. Point bar architectural motifs are locally abundant in the unit and this is attributed to elevated amounts of mud-calibre cohesive sediment. Mud afforded landscape stability that, together with limited stream power, was sufficient to corral sediment into single-thread, sinuous channels. Significant volumes of fine-grained sediment were encouraged to accumulate by the local basin setting of several topographically confined endorheic depressions. These conditions ceased once the hydrologically closed valleys were filled, with the overlying sandstone-dominated Applecross Formation subsequently deposited by low-sinuosity, braided rivers that bypassed fine-grained sediment oceanward. Other endorheic basins conducive to the formation of depositional meanders should be expected to have been relatively widespread on pre-vegetation Earth, though many individually limited in size, confined by their inherited topographies. Depositional architectures representative of sinuous channel planforms remain scarce within more extensive, externally drained basins.

This paper forensically reconstructs the timings, impacts and processes that drove the sequence of explosive eruptions of La Soufrière, St Vincent in April 2021 using a combination of field-based stratigraphy and textural dissection of the deposit character together with contemporary visual observations. Explosive activity on 9th and early on 10th April involved destruction of almost all of the 2020/2021 lava dome, ∼ 60% of the 1979 dome and formation of a 600 m diameter crater by 2pm UTC on 10th April. Following the initial explosion, plumes rose to altitudes of ∼15 km and pyroclastic density currents (PDCs) formed by column collapse, first occurred on 10th April, only after > 24hrs of explosive activity. Dense PDCs reached the sea only in the Larikai and Roseau Valleys, and dilute PDCs were restricted to within 2.5 km of the Summit Crater rim. The tephra fallout deposits are stratified, composed of numerous layers of both lapilli-rich and ash-rich layers, which we have grouped into at least 7 Units, based on their common characteristics (Units 1 to 7). Volume estimates, using a range of techniques to constrain uncertainties, indicate that the bulk volume of tephra (fallout and PDC) is 1.19 x 108m3 +/− 20% making this a VEI 4 eruption. Supplementary material at https://doi.org/10.6084/m9.figshare.c.6474317

Human activity can protect or harm marine environments, with far-reaching impacts not only on the marine ecosystem but also on human health and well-being. One way to integrate both Sustainable Development Goals—marine protection and public health—may be individuals’ physical (marine contact) and psychological (inclusion of marine environments in self-representation) connectedness with marine environments. Using secondary data from surveys in 14 European countries and Australia (N ≈ 15,000), we will investigate the relationships of physical (Study 1) and psychological (Study 2) marine connectedness with public perceptions of marine protection importance as well as general health and well-being.

[Introduction] The Help directed by Tate Taylor and based off Kathryn Stockett’s novel portrays an incomplete narrative of Black women’s domestic work in white households through a white feminist lens under the backdrop of the 1963 Civil Rights Movement. While the movie seeks to show the perspective of these Black women often ignored throughout history, the movie instead focuses largely on an upcoming white woman writer named Skeeter. To shape Skeeter’s ultimate writing success story, the movie utilizes the Civil Rights Movement and the Black domestic workers, mainly Aibileen and Minny, to jumpstart Skeeter’s writing career, subsequently leaving the Black community to deal with the aftermath of the publication of Skeeter’s novel. Based in Jackson, Mississippi, The Help details the racial turmoil of the time through the grossly comic portrayal of outdoor bathrooms for the domestic workers, the unrealistic arrest of Yule Mae Davis, and the turbulent assassination of Medgar Evers. While Medgar Evers killing was historically accurate, the oversimplification of white allyship, Black resistance, and the softening of segregation and discrimination allow the audience to feel a false sense of accomplishment at the end of the movie which would realistically end in bloodshed. Although The Help builds its story around various key aspects of the Civil Rights movement in 1963, the movie substantially underplays the intensity of discrimination against Black people by heavily filtering the movement to craft an agreeable Hollywood narrative.

Objectives: Multiple health behaviour change is a viable strategy to promote health outcomes. An example is the use of running behaviour to support smoking cessation in the group-mediated Run to Quit program. On the basis that changes in running and smoking identity were related to changes in running and smoking behaviour among individuals in the Run to Quit program, the purpose of this study was to extend these findings by examining key predictors of change in both running and smoking identity. Methods: We analyzed data collected from 450 adult individuals (70.67% female, and 92.44% white) during the program evaluation of Run to Quit from 2016 to 2018. Participants completed assessments at week 1 (baseline), week 3 (mid-program), and week 10 (follow-up) of the program. Relevant predictor variables for change in identity were identified by drawing from theory (identity theory, identity control theory, physical activity self-definition model, social identity theory) and past research regarding exercise and smoking identity. Potential predictors of changes in running and smoking identity included changes in behaviour, self-efficacy, perceptions of the social environment (task and social cohesion, descriptive norms), as well as smoking identity and running identity, respectively. Two regression models, using residualized change scores (for each variable) and relative Pratt indices, were constructed 15 for both running and smoking identity. Results: Changes in running self-efficacy, running frequency, and individual attractions to the group exercise tasks were significant and meaningful predictors of change in running identity, whereas changes in objectively measured smoking behaviour and running identity were significant and meaningful predictors of change in smoking identity. Conclusion: Consistent with identity theories and past research, ensuring individuals develop a sense of efficacy and enjoy group exercise tasks both represent viable strategies to enhance exercise identity. Including an exercise component within smoking cessation programs may help individuals replace their existing smoking identity with a healthier exercise identity.

Endogenous endophthalmitis (EE) is a rare infectious disease of the intraocular tissues with a major risk of significant visual loss. We describe a case of a female patient who presented with altered mental status and vision loss. The patient was found to have bacteraemia, meningitis and bilateral EE caused by

Vaccination remains key to reducing the risk of COVID-19–related severe illness and death. Because of historic medical exclusion and barriers to access, Black communities have had lower rates of COVID-19 vaccination than White communities. We describe the efforts of an academic medical institution to implement community-based COVID-19 vaccine clinics in medically underserved neighborhoods in Philadelphia, Pennsylvania. Over a 13-month period (April 2021–April 2022), the initiative delivered 9038 vaccine doses to community members, a majority of whom (57%) identified as Black. (Am J Public Health. 2022;112(12):1721–1725. https://doi.org/10.2105/AJPH.2022.307030 )

A toddler presented with melaena on a background of a possible enteric duplication cyst, diagnosed in the neonatal period which ‘vanished’. What was later confirmed to be a small bowel duplication cyst was not seen on follow-up ultrasounds and thus the patient was managed expectantly until presentation as an emergency. Our case highlights the challenges faced in managing cystic abdominal structures in infancy and the potential consequences of expectant management. We discuss whether cross-sectional imaging or diagnostic laparoscopy should be advocated when duplications cysts are considered amongst the differentials of a lesion on ultrasound.

Haemophagocytic lymphocytic histiocytosis (HLH) is a rare, life-threatening condition caused by abnormal activation of cytotoxic T lymphocytes, natural killer cells and macrophages resulting in hypercytokinaemia and immune-mediated injury of multiple organ systems. Secondary HLH occurs in the setting of a malignant, infectious or autoimmune stimulus. Macrophage activation syndrome (MAS) is the term used to describe HLH that develops secondary to rheumatological diseases such as lupus and juvenile idiopathic arthritis, among others. Commonly observed and documented symptoms include fever, organomegaly and lymphadenopathy. Given the potential for multiorgan failure in HLH/MAS, early identification, diagnosis and initiation of treatment is essential. We present a case of secondary HLH/MAS with acute inflammatory gastroenteritis in a middle-aged woman with a history of systemic lupus erythematosus.

Wound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix molecules regulated by the actin cytoskeleton. This microscopic network of filaments is present within the cytoplasm of all cells and provides the shape and mechanical support required for cell movement and proliferation. Here, an overview of the processes of wound healing are described from the perspective of the cell in relation to the actin cytoskeleton. Key points of discussion include the role of actin, its binding proteins, signaling pathways, and events that play significant roles in the phases of wound healing. The identification of cytoskeletal targets that can be used to manipulate and improve wound healing is included as an emerging area of focus that may inform future therapeutic approaches to improve healing of complex wounds. Refereed/Peer-reviewed

The rapid emergence of COVID-19 in the Spring of 2020 forced a majority of academic institutions, teachers, administrators, and students to precipitously move to online learning. In that sudden move, cloud-based video conferencing technology, allowing teachers and students to interact live with one another, became the technology of choice for many. The key factor that precipitated the move to video conferencing technology in schools was the ability to humanize online learning and provide a live visual link between teacher and students. This chapter describes each element of R2D2/C3PO, a research-based, validated, instructional design model, in-depth, providing generic examples of instructional strategies and learning activities for each element. The overarching objective of this article is to list and describe each model component, which are read, reflect, display, do, coaching, conviviality, critical incident questionnaire, planning, and organization, and then to provide detailed descriptions of constructivist instructional strategies and learning activities that can be used.

The apparent virilization of the female spotted hyena raises questions about sex differences in behavior and morphology. We review these sex differences to find a mosaic of dimorphic traits, some of which conform to mammalian norms. These include space-use, dispersal behavior, sexual behavior, and parental behavior. By contrast, sex differences are reversed from mammalian norms in the hyena's aggressive behavior, social dominance, and territory defense. Androgen exposure early in development appears to enhance aggressiveness in female hyenas. Weapons, hunting behavior, and neonatal body mass do not differ between males and females, but females are slightly larger than males as adults. Sex differences in the hyena's nervous system are relatively subtle. Overall, it appears that the "masculinized" behavioral traits in female spotted hyenas are those, such as aggression, that are essential to ensuring consistent access to food; food critically limits female reproductive success in this species because female spotted hyenas have the highest energetic investment per litter of any mammalian carnivore. Evidently, natural selection has acted to modify traits related to food access, but has left intact those traits that are unrelated to acquiring food, such that they conform to patterns of sexual dimorphism in other mammals.

After more than three months of lava dome extrusion, La Soufrière (St. Vincent) transitioned to a series of explosive eruptions in April 2021. Here we present a time-series petrologic analysis of the phenocryst and microlite populations during the first ∼48 hours of explosivity to constrain ascent conditions and processes that drove changes in behavior. Primary eruptive products were crystal-rich (45-50 vol%) basaltic andesites with similar phenocryst phase assemblages and compositions. The change in eruptive style is consistent with overpresurization as a consequence of second boiling from anhydrous microlite crystallization. The microlites display variation between the explosive phases, with two populations: 1) “inherited” - normally zoned high-An plagioclase (>An70) + olivine (Fo62-79) + clinopyroxene + titanomagnetite, inferred to have crystallized at depths >15 km and high water pressures; 2) “juvenile” - unzoned plagioclase (An45-65) + clinopyroxene + orthopyroxene + intermediate pyroxene (Wo12-38) + titanomagnetite, inferred to have crystallized upon ascent due to decompression and degassing. Scoria from the first explosions featured extensive groundmass crystallization and a significant “inherited” microlite population. Later explosions had a more abundant “juvenile” microlite population and lower crystallinity, consistent with more rapid ascent from depth, initiated by decompression following initial blasts and destruction of the lava dome. Supplementary material at https://doi.org/10.6084/m9.figshare.c.6534864

Objective: To evaluate the effects of uncoupling protein (UCP) 1, UCP2 and UCP3 gene variants on body composition and metabolic changes in response to chronic overfeeding and the recovery after the period of overfeeding. Subjects and design: Twenty-four normal weight men (21±2 y), who constituted 12 pairs of identical twins, ate a 4.2 MJ/day energy surplus, 6 days a week, during a period of 100 days. The subjects were asked to return to the laboratory for testing at 4 months and for a final examination 5 y after completion of the overfeeding protocol. Methods: Resting metabolic rate (RMR) measurements were performed before and after overfeeding. A 4.2 MJ test meal was consumed, after which calorimetric measurements were continued for 240 min. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Polymorphisms were typed by PCR and PCR-RFLP-techniques. Thyroid stimulating hormone (TSH) concentrations after a thyrotropin releasing hormone (TRH) injection were measured by radioimmunoassay (RIA). Results: The changes in body weight and adiposity were not different between UCP1 Bcl I, UCP2 alanine to valine (A55V), UCP2 insertion/deletion (I/D) or UCP3 Rsa I genotypes. However, the recovery from overfeeding was worse among G-allele carriers of the UCP1 Bcl I, I allele non-carriers of the UCP2 I/D, AV heterozygote subjects of the UCP2 A55V and CC subjects of the UCP3 Rsa I polymorphisms. RMR was lower both before (P=0.01) and after (P=0.001) overfeeding in subjects with the CC genotype of the UCP3 Rsa I polymorphism. Moreover, after overfeeding, the UCP2 A55V heterozygote and UCP3 Rsa I CC homozygote subjects had significantly higher respiratory quotient (RQ) values at rest (P

Abstract: The fabrication of polymer fibre blends has gained much attention for the development of innovative nanomaterials. Polymer fibre blends are nanomaterials with different functionalities and properties such as a sizeable surface-to-area ratio, high porosity, flexibility, and stability. The focus of this study was to produce zein/PVA fibre blends using the electrospinning technique and varying parameters such as concentration and applied voltage. The two parameters are key driving factors for the production of fibres. Zein as a natural polymer has challenges in developing fibre materials which require artificial polymer like PVA to create a good blending mixture for electrospinning. Methods: The zein/PVA nanofibre blends were fabricated using the electrospinning technique. The FE-SEM (Leo, Zeiss) was used to study the surface morphologies of the zein/PVA nanofibers blends. The optical properties of the nanofibre blends were determined using the UV-vis spectrophotometer and the chemical structure and composition of zein/PVA nanofibers blends were studied using Thermo Scientific Nicolet iS50-FTIR spectrometer, universal ATR with the diamond detector. Results: The SEM images showed smooth zein/PVA ribbon-like nanofibre blends of 90/10, 80/20, 70/30, 60/40, and 50/50. SEM images of zein/PVA (80/20) electrospun at 25 kV were obtained to be the maximum fibre yield due to zein/PVA compatibility, increased conductivity, and enhanced fibre formation. The optical properties (absorption spectroscopy) suggested that the zein/PVA (80/20) fibre blend was miscible, and the FTIR spectra confirmed their functional groups. Therefore, the characterization results showed that the polymer blended solutions concentration and applied voltage increment affected fibre size distribution and morphology. Conclusion: Optimizing concentration and applied voltage successfully produced smooth, uniform bead-free zein/PVA fibre blends as parameters are increased.

Posterior distributions for community structure in sparse planted bi-section models are shown to achieve exact (resp. almost-exact) recovery, with sharp bounds for the sparsity regimes where edge probabilities decrease as $O(\log(n)/n)$ (resp. $O(1/n)$). Assuming posterior recovery, one may interpret credible sets (resp. enlarged credible sets) as asymptotically consistent confidence sets; the diameters of those credible sets are controlled by the rate of posterior concentration. If credible levels are chosen to grow to one quickly enough, corresponding credible sets can be interpreted as frequentist confidence sets without conditions on posterior concentration. In the regimes with $O(1/n)$ edge sparsity, or when within-community and between-community edge probabilities are very close, credible sets may be enlarged to achieve frequentist asymptotic coverage, also without conditions on posterior concentration., 29 pp., 3 fig

The water systems inside a dental unit are known to be contaminated with a multi-kingdom biofilm encompassing bacteria, fungi, viruses and protozoa. Aerosolization of these micro-organisms can potentially create a health hazard for both dental staff and the patient. Very little is known on the efficacy of dental unit disinfection products against amoeba. In this study we have examined the effect of four different treatment regimens, with the hydrogen peroxide (H2O2) containing product Oxygenal, on an in-vitro multi-kingdom dental unit water system (DUWS) biofilm. The treatment efficacy was assessed in time using heterotrophic plate counts, the bacterial 16S rDNA, fungal 18S rDNA gene load and the number of genomic units for Legionella spp. the amoeba Vermamoeba vermiformis. The results indicated that a daily treatment of the DUWS with a low dose H2O2 (0.02% for 5 h), combined with a weekly shock dose (0.25% H2O2, 30 min) is necessary to reduce the heterotrophic plate count of a severely contaminated DUWS (>106 CFU.mL−1) to below 100 CFU.mL−1. A daily treatment with a low dose hydrogen peroxide alone, is sufficient for the statistically significant reduction of the total amount of bacterial 16S rDNA gene, Legionella spp. and Vermamoeba vermiformis load (p < 0.005). Also shown is that even though hydrogen peroxide does not kill the trophozoite nor the cysts of V. vermiformis, it does however result in the detachment of the trophozoite form of this amoeba from the DUWS biofilm and hereby ultimately removing the amoeba from the system.

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare peroxisomal disorder causing pristanic acid accumulation. Only 16 cases have been described so far. A female in her seventh decade presented with episodes of dysphasia, headache and sensory disturbance inconsistent with migraine, epilepsy or transient ischaemic attack. An MRI demonstrated unusual changes in the pons, red nuclei, thalami and white matter. Mitochondrial disease was suspected but detailed testing was negative. After eight years of symptoms, she developed a febrile encephalopathy with hemispheric dysfunction, focal convulsive seizures and coma. Her condition stabilised after one month. Lacosamide was continued for seizure prevention. The diagnosis remained elusive until whole genome sequencing revealed AMACR deficiency. Pristanic acid levels were highly elevated and dietary modification was recommended. Genetic peroxisomal disorders can present in older age; our patient is the oldest in the AMACR deficiency literature. Novel features in our case include central apnoea, dystonia and rapid eye movement behaviour disorder.

Ocular surface melanoma (OSM) is rare. An 81-year-old Caucasian woman presented with a 4-month history of right eye pain and reduced vision. Histopathological examination of the excisional biopsy identified invasive amelanotic melanoma of the conjunctiva expressing Melan A and SOX10. X-ray of chest, CT of liver and MRI of the brain and orbit did not identify macroscopic metastases. She was given adjuvant topical mitomycin-C 0.04% for four cycles of 2 weeks. Her vision improved and the cornea was clear at 6 months.

Funder: Amazon Web Services (AWS) Imagine Grant, Funder: Kingston University (Kingston University, London); doi: https://doi.org/10.13039/100010049, Funder: Association Nationale de la Recherche et de la Technologie (National Association for Research and Technology); doi: https://doi.org/10.13039/501100003032, Funder: Association Nationale de la Recherche Scientifique and Pacifica (CIFRE grant 2017/0245), Funder: PRIMUS/20/HUM/009, Funder: UID/PSI/03125/2019 from the Portuguese National Foundation for Science and Technology (FCT)., Funder: PSA research grant ($285.59) for the PSACR projects data collection, Funder: The work of Dmitrii Dubrov was supported within the framework of the Basic Research Program at HSE University, RF, Funder: Agentúra na podporu výskumu a vývoja (Slovak Research and Development Agency) - APVV-17-0596, Funder: Progres Q18, Charles University, Funder: JSPS KAKENHI Grant Numbers JP18K12015 and JP20H04581, Funder: National Science Centre, Poland (2019/35/B/HS6/00528), Funder: Slovak Research and Development Agency - APVV-17-0596, Funder: Huo Family Foundation, Funder: The Japan Society for the Promotion of Science KAKENHI [19K14370], Funder: The Institute of Psychology, Jagiellonian University, Funder: Program FUTURE LEADER of Lorraine Université d’Excellence within the program Investissements Avenir (ANR-15-IDEX-04-LUE) operated by the French National Research Agency, Funder: Rubicon grant (019.183SG.007) from the Netherlands Organization for Scientific Research (NWO), Funder: Australian Research Council (DP180102384), Funder: HSE University Basic Research Program, Funder: Horizon 2020 grant 964728 (JITSUVAX) from the European Commission and was supported by a United Kingdom Research and Innovation (UKRI) Research Fellowship grant ES/V011901/1, Funder: Social Science and Humanities Research Council of Canada, Funder: Dominican University Faculty Support Grant, Funder: FONDECYT 1221538, Funder: Vicerrectoria de Investigaciones, Uniandes, Funder: Statutory funds of the Institute of Psychology, University of Wroclaw, Funder: University of Desarrollo, Faculty of Psychology, Funder: IDN Being Human Lab (University of Wrocław), Funder: ANID - Fondecyt 1201513, In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.

Background Colorectal cancer (CRC) can be divided into four consensus molecular subtypes (CMS), each with distinct biological features. CMS4 is associated with epithelial-mesenchymal transition and stromal infiltration (Guinney et al., Nat Med 21:1350–6, 2015; Linnekamp et al., Cell Death Differ 25:616–33, 2018), whereas clinically it is characterized by lower responses to adjuvant therapy, higher incidence of metastatic spreading and hence dismal prognosis (Buikhuisen et al., Oncogenesis 9:66, 2020). Methods To understand the biology of the mesenchymal subtype and unveil specific vulnerabilities, a large CRISPR-Cas9 drop-out screen was performed on 14 subtyped CRC cell lines to uncover essential kinases in all CMSs. Dependency of CMS4 cells on p21-activated kinase 2 (PAK2) was validated in independent 2D and 3D in vitro cultures and in vivo models assessing primary and metastatic outgrowth in liver and peritoneum. TIRF microscopy was used to uncover actin cytoskeleton dynamics and focal adhesion localization upon PAK2 loss. Subsequent functional assays were performed to determine altered growth and invasion patterns. Results PAK2 was identified as a key kinase uniquely required for growth of the mesenchymal subtype CMS4, both in vitro and in vivo. PAK2 plays an important role in cellular attachment and cytoskeletal rearrangements (Coniglio et al., Mol Cell Biol 28:4162–72, 2008; Grebenova et al., Sci Rep 9:17171, 2019). In agreement, deletion or inhibition of PAK2 impaired actin cytoskeleton dynamics in CMS4 cells and, as a consequence, significantly reduced invasive capacity, while it was dispensable for CMS2 cells. Clinical relevance of these findings was supported by the observation that deletion of PAK2 from CMS4 cells prevented metastatic spreading in vivo. Moreover, growth in a model for peritoneal metastasis was hampered when CMS4 tumor cells were deficient for PAK2. Conclusion Our data reveal a unique dependency of mesenchymal CRC and provide a rationale for PAK2 inhibition to target this aggressive subgroup of colorectal cancer.