Miracle-dz/UniFAR-FTUs huggingface dataset:
Repurposing of anticancer drugs expands possibilities for antiviral and anti-inflammatory discovery in COVID-19.

In 2020, the COVID-19 pandemic led to an unprecedented destabilization of the world's health and economic systems. The rapid spread and life-threatening consequences of COVID-19 have imposed a repurposing drug testing, by investigating drugs already used in other indications, including anti-cancer drugs. Anti-cancer drug repurposing started to contour after deciphering similarities between COVID-19 and malignancies pathogenesis, including abnormal inflammatory and immunological responses. In this review we will discuss the salient positive and negative points of repurposing the main anticancer drugs to further treat COVID-19.
Prevalence and genotype distribution of high‐risk HPV infection among women in Beijing, China

Cervical cancer (CC) is highly associated with high‐risk human papillomavirus (HPV) infection and genotype distribution of high‐risk HPV (HR‐HPV) infection varies greatly in different regions. Clinical specimens were collected from 46 365 patients at Beijing Friendship Hospital, Capital Medical University from January 2017 to December 2020. HPV DNA genotype testing was performed using real‐time PCR. The infection rates based on disease group were compared using the χ 2 test. The linear‐by‐linear association test and gamma value were used to assess the changes in HPV prevalence over calendar year and age group. A total of 10 514 women were infected with HR‐HPV, with an overall positive rate of 22.7%. The most prevalent HR‐HPV types were HPV52, 58, 16, 51, and 66, and HPV59 had a higher prevalence except for HPV16, 58, and 52 in the CC group. Single infection of HR‐HPV was dominant among different disease groups. The infection rate of HR‐HPV decreased first and then increased from below 20 years old to over 60 years old. There were significant differences in the HR‐HPV infection rates among the age and disease groups. Our findings demonstrate that the genotype distribution of HR‐HPV varied with age and diseases. The HR‐HPV genotypes prevalence was found to be directly useful for local governments to promote HPV targeted vaccination in the study region.
Quantifying high‐temperature stress on soybean canopy photosynthesis: The unique role of sun‐induced chlorophyll fluorescence

High temperature and accompanying high vapor pressure deficit often stress plants without causing distinctive changes in plant canopy structure and consequential spectral signatures. Sun‐induced chlorophyll fluorescence (SIF), because of its mechanistic link with photosynthesis, may better detect such stress than remote sensing techniques relying on spectral reflectance signatures of canopy structural changes. However, our understanding about physiological mechanisms of SIF and its unique potential for physiological stress detection remains less clear. In this study, we measured SIF at a high‐temperature experiment, Temperature Free‐Air Controlled Enhancement, to explore the potential of SIF for physiological investigations. The experiment provided a gradient of soybean canopy temperature with 1.5, 3.0, 4.5, and 6.0°C above the ambient canopy temperature in the open field environments. SIF yield, which is normalized by incident radiation and the fraction of absorbed photosynthetically active radiation, showed a high correlation with photosynthetic light use efficiency (r = 0.89) and captured dynamic plant responses to high‐temperature conditions. SIF yield was affected by canopy structural and plant physiological changes associated with high‐temperature stress (partial correlation r = 0.60 and −0.23). Near‐infrared reflectance of vegetation, only affected by canopy structural changes, was used to minimize the canopy structural impact on SIF yield and to retrieve physiological SIF yield (ΦF) signals. ΦF further excludes the canopy structural impact than SIF yield and indicates plant physiological variability, and we found that ΦF outperformed SIF yield in responding to physiological stress (r = −0.37). Our findings highlight that ΦF sensitively responded to the physiological downregulation of soybean gross primary productivity under high temperature. ΦF, if reliably derived from satellite SIF, can support monitoring regional crop growth and different ecosystems' vegetation productivity under environmental stress and climate change.
Corrective attachment episodes in attachment-based family therapy: the power of enactment

Abstract Corrective attachment episodes, therapeutic enactments designed to increase openness and trust between young adults and their parents, are the purported primary change mechanism in attachment-based family therapy. This study examined whether sequences of therapist interventions, young adults’ productive emotional processing, and parental behaviors thought to reflect corrective attachment episodes were characteristic of good versus poor outcome cases. Thirty conjoint attachment sessions were analyzed using the THEME algorithm. Results revealed that only in good outcome cases were there four-step sequences hypothesized to facilitate attachment. One sequence began with the therapist focusing on the young adult’s primary adaptive emotions, followed by the young adult’s productive emotional processing of their vulnerable emotions, followed by the therapist empathizing with and validating the parent, followed by parents’ expressions of warmth toward their young adult. The second sequence began with the therapist focusing on the young adult’s unmet attachment needs, followed by the young adult productively processing their vulnerable emotions, followed by the parent expressing a willingness to fulfill their young adult’s attachment needs, followed by parents’ expressions of warmth toward their young adult. Findings provide an empirically-based clinical map for conducting therapeutic enactments in family therapy and have implications for treatment development, therapist training and supervision.
Experiences and emotional strain of NHS frontline workers during the peak of the COVID-19 pandemic

Background: The mental health of the population has been negatively affected due to the pandemic. Frontline healthcare workers with increased exposure to COVID diagnosis, treatment and care were especially likely to report psychological burden, fear, anxiety and depression. Aim: To elicit how working as a health professional during the pandemic is impacting on the psychological wellbeing of frontline staff. Method: United Kingdom population of healthcare workers were approached by advertising the survey via social media, NHS trusts and other organisations. Open-ended survey answers were qualitatively explored using content analysis. Results: Survey collected data from 395 NHS staff was developed into three themes; (1) Despair and uncertainty: feeling overwhelmed trying to protect everyone, (2) Behavioural and psychological impact: affecting wellbeing and functioning and (3) Coping and employer support: getting the right help. Conclusion: NHS staff felt enormous burden to adequately complete their professional, personal and civil responsibility to keep everyone safe leading to negative psychological and behavioural consequences and desire for NHS employers to offer better support. As the pandemic progresses, the results of this study may inform NHS employers on how optimum support can be offered to help them cope with negative psychological consequences of the pandemic.
Red meat consumption, cooking mutagens, NAT1/2 genotypes and pancreatic cancer risk in two ethnically diverse prospective cohorts

There is limited evidence on the association between red meat consumption and pancreatic cancer among ethnic minorities. We assessed this relationship in two large prospective cohorts: the Multiethnic Cohort Study (MEC) and the Southern Community Cohort Study (SCCS). Demographic, dietary and other risk factor data were collected at cohort entry. Red meat intake was assessed using cohort‐specific validated food frequency questionnaires. Incident pancreatic cancer cases were identified via linkages to state cancer registries. Cox regression was used to calculate relative risks (RRs) and 95% confidence intervals (CIs) for the association of red meat intake with pancreatic cancer risk in each cohort. We performed additional analyses to evaluate cooking methods, mutagens and effect modification by NAT1/2 genotypes. From a total of 184 542 (MEC) and 66 793 (SCCS) at‐risk participants, we identified 1618 (MEC) and 266 (SCCS) incident pancreatic cancer cases. Red meat consumption was associated with pancreatic cancer risk in the MEC (RRQ4vsQ1 1.18, 95% CI 1.02‐1.37) and with borderline statistical significance in the SCCS (RRQ4vsQ1 1.31, 95% CI 0.93‐1.86). This association was significant in African Americans (RRQ4vsQ1 1.49, 95% CI 1.06‐2.11) and Latinos (RRQ4vsQ1 1.44, 95% CI 1.02‐2.04) in the MEC, and among African Americans (RRQ4vsQ1 1.55, 95% CI 1.03‐2.33) in the SCCS. NAT2 genotypes appeared to modify the relationship between red meat and pancreatic cancer in the MEC (pinteraction = 0.03). Our findings suggest that the associations for red meat may be strongest in African Americans and Latinos. The mechanisms underlying the increased risk for these populations should be further investigated.
Destination safety climate: scale development and validation

ABSTRACT Destination safety is crucial for destination management. However, measurement scales for destination safety climate are absent. Thus, the purpose of this study was to develop a destination safety climate scale, based on tourism-stakeholder perspectives. Through a rigorous development process, the 31-item seven-dimensional destination safety climate scale was proven to have validity and reliability. This study contributes to the theoretical literature on safety climate, in addition to further study of the relationships between destination safety climate and other relevant constructs. The findings of this study can serve as a reference for destination managers and travel suppliers in terms of safety management.
Research note: the role of willingness to communicate in cross-cultural adaptation

ABSTRACT Despite widely reported ‘Mainland-Hong Kong conflicts’, recent years have witnessed progressive growth of Mainland Chinese students in Hong Kong universities. This study aims to explore the role of Willingness to Communicate (WTC) in the cross-cultural adaptation of such a group of sojourning students. Structural equation modelling showed that the competence in L2 communication played a significant role in L2 WTC, which had an influential effect on academic adaptation, which was itself identified as a mediator between psychological adaptation and socio-cultural adaptation. Implications for curriculum design and instructional practice on international students are discussed.
The extended self-identify- based electric product adoption model and airline business strategy: A new theoretical framework for green technology products

ABSTRACT This study developed a framework of the self-identity-based electric product adoption model to comprehend air travelers’ intentions to adopt eco-friendly electric airplanes. Through a quantitative process and survey method, our analysis revealed that the model satisfactorily accounted for the travelers’ eco-friendly airplane adoption intentions. The model comprised the concepts of green self-identity, care for environmental consequences, green moral obligation, attitude, and anticipated feelings. Moreover, we extended the model by considering the moderating impact of perceived risks. Overall, this study successfully provided a sufficient understanding of travelers’ eco-friendly technology product adoption behaviors in the airline context.
Layaway Freedom: Coercive Financialization in the Criminal Legal System1

Economic sociologists have documented the rise of financialization, including credit and debt. In the case of monetary sanctions in the criminal legal system, courts frequently extend payment plans—or “layaway”—as a way for defendants to manage financial court debt and gain their freedom. Using 241 hours of courtroom ethnography and 155 interviews with court actors and people paying their court debt in Illinois, the authors offer a microsociology of financialization that shows how the creditor/debtor relationship commodifies freedom, confuses and suffuses court processes, amplifies control, and expands the financial sector into domains that obligate participation. Layaway freedom represents a case of coercive financialization, or the externally imposed, involuntary, or last-resort entry into financial engagements. The manipulation of money and time achieves disproportionate punishment that is multiplicative, rather than simply additive, all under the guise of routine financial responsibility. The authors discuss implications of these concepts for both economic and criminal-legal sociology.
Constraints and variation in food web link-species space

Predicting food web structure in future climates is a pressing goal of ecology. These predictions may be impossible without a solid understanding of the factors that structure current food webs. The most fundamental aspect of food web structure—the relationship between the number of links and species—is still poorly understood. Some species interactions may be physically or physiologically ‘forbidden'—like consumption by non-consumer species—with possible consequences for food web structure. We show that accounting for these ‘forbidden interactions' constrains the feasible link-species space, in tight agreement with empirical data. Rather than following one particular scaling relationship, food webs are distributed throughout this space according to shared biotic and abiotic features. Our study provides new insights into the long-standing question of which factors determine this fundamental aspect of food web structure.
Declining greenness in Arctic-boreal lakes

Significance Arctic and boreal regions are undergoing dramatic warming and also possess the world’s highest concentration of lakes. However, ecological changes in lakes are poorly understood. We present a continental-scale trend analysis of satellite lake color in the green wavelengths, which shows declining greenness from 1984 to 2019 in Arctic-boreal lakes across western North America. Annual 30-m Landsat composites indicate lake greenness has decreased by 15%. Our findings show a relationship between lake color, rising air temperatures, and increasing precipitation, supporting the theory that warming may be increasing connectivity between lakes and surrounding landscapes. Overall, our results bring a powerful set of observations in support of the hypothesis that lakes are sentinels for global change in rapidly warming Arctic-boreal ecosystems. The highest concentration of the world’s lakes are found in Arctic-boreal regions [C. Verpoorter, T. Kutser, D. A. Seekell, L. J. Tranvik, Geophys. Res. Lett. 41, 6396–6402 (2014)], and consequently are undergoing the most rapid warming [J. E. Overland et al., Arctic Report Card (2018)]. However, the ecological response of Arctic-boreal lakes to warming remains highly uncertain. Historical trends in lake color from remote sensing observations can provide insights into changing lake ecology, yet have not been examined at the pan-Arctic scale. Here, we analyze time series of 30-m Landsat growing season composites to quantify trends in lake greenness for >4 × 105 waterbodies in boreal and Arctic western North America. We find lake greenness declined overall by 15% from the first to the last decade of analysis within the 6.3 × 106-km2 study region but with significant spatial variability. Greening declines were more likely to be found in areas also undergoing increases in air temperature and precipitation. These findings support the hypothesis that warming has increased connectivity between lakes and the land surface [A. Bring et al., J. Geophys. Res. Biogeosciences 121, 621–649 (2016)], with implications for lake carbon cycling and energy budgets. Our study provides spatially explicit information linking climate to pan-Arctic lake color changes, a finding that will help target future ecological monitoring in remote yet rapidly changing regions.
Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease

Significance Mendelian susceptibility to mycobacterial disease (MSMD) is defined by selective vulnerability to weakly virulent mycobacteria. The 32 known inborn errors of IFN-γ immunity account for MSMD in about half of the patients, and for a smaller proportion of cases of tuberculosis (TB). We report homozygous ZNFX1 variants in two families in which the index cases had MSMD or TB with intermittent monocytosis. Upon overexpression, the two variants encode truncated proteins. We show that human ZNFX1 is localized in ribonucleoprotein granules called stress granules. The patients’ production of and response to IFN-γ are apparently intact, and the patients have not experienced severe viral illnesses. Inherited deficiency of stress granule-associated ZNFX1 is a genetic etiology of MSMD or TB with intermittent monocytosis. Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient IFN-γ production by lymphoid cells, impaired myeloid cell responses to this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette–Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. The patients are homozygous for ZNFX1 variants (p.S959* and p.E1606Rfs*10) predicted to be loss of function (pLOF). There are no subjects homozygous for pLOF variants in public databases. ZNFX1 is a conserved and broadly expressed helicase, but its biology remains largely unknown. It is thought to act as a viral double-stranded RNA sensor in mice, but these patients do not suffer from severe viral illnesses. We analyze its subcellular localization upon overexpression in A549 and HeLa cell lines and upon stimulation of THP1 and fibroblastic cell lines. We find that this cytoplasmic protein can be recruited to or even induce stress granules. The endogenous ZNFX1 protein in cell lines of the patient homozygous for the p.E1606Rfs*10 variant is truncated, whereas ZNFX1 expression is abolished in cell lines from the patients with the p.S959* variant. Lymphocyte subsets are present at normal frequencies in these patients and produce IFN-γ normally. The hematopoietic and nonhematopoietic cells of the patients tested respond normally to IFN-γ. Our results indicate that human ZNFX1 is associated with stress granules and essential for both monocyte homeostasis and protective immunity to mycobacteria.
Capture and metabolomic analysis of the human endometrial epithelial organoid secretome

Significance The ability to robustly isolate intraorganoid fluid in a high-throughput capacity, using human endometrial epithelia as a model, circumvents several constraints typically associated with obtaining biological fluids, both in vivo and in vitro. This approach also allows for direct tandem genomics, transcriptomics, proteomics, and functional metabolomics. In addition to enhancing our understanding of uterine fluid composition regulation, this innovation is directly and readily transferrable to wider fields of cell and organoid biology, with implications for personalized, or precision, medicine approach development. Suboptimal uterine fluid (UF) composition can lead to pregnancy loss and likely contributes to offspring susceptibility to chronic adult-onset disorders. However, our understanding of the biochemical composition and mechanisms underpinning UF formation and regulation remain elusive, particularly in humans. To address this challenge, we developed a high-throughput method for intraorganoid fluid (IOF) isolation from human endometrial epithelial organoids. The IOF is biochemically distinct to the extraorganoid fluid (EOF) and cell culture medium as evidenced by the exclusive presence of 17 metabolites in IOF. Similarly, 69 metabolites were unique to EOF, showing asymmetrical apical and basolateral secretion by the in vitro endometrial epithelium, in a manner resembling that observed in vivo. Contrasting the quantitative metabolomic profiles of IOF and EOF revealed donor-specific biochemical signatures of organoids. Subsequent RNA sequencing of these organoids from which IOF and EOF were derived established the capacity to readily perform organoid multiomics in tandem, and suggests that transcriptomic regulation underpins the observed secretory asymmetry. In summary, these data provided by modeling uterine luminal and basolateral fluid formation in vitro offer scope to better understand UF composition and regulation with potential impacts on female fertility and offspring well-being.
4E-BP2–dependent translation in parvalbumin neurons controls epileptic seizure threshold

Significance In numerous models of neurodevelopmental disorders and epilepsy, genetic mutations associated with enhanced mTORC1 activity engender an increase in the susceptibility to epileptic seizures. This study shows that the deletion of the mTORC1-downstream translational repressor, 4E-BP2, but not 4E-BP1, promotes epileptogenesis. By deleting 4E-BP2 in different cell types, we reveal that the up-regulation of mTORC1/eIF4E signaling in parvalbumin inhibitory neurons is sufficient to reduce the threshold for the induction of seizures. We conclude that downstream of mTORC1, 4E-BP2 is the main 4E-BP paralog controlling epileptogenesis and propose that parvalbumin inhibitory neurons are a vulnerable cell type in which the aberrant activation of mTORC1-dependent translation contributes to epileptic pathology. The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals to regulate critical cellular processes such as mRNA translation, lipid biogenesis, and autophagy. Germline and somatic mutations in mTOR and genes upstream of mTORC1, such as PTEN, TSC1/2, AKT3, PIK3CA, and components of GATOR1 and KICSTOR complexes, are associated with various epileptic disorders. Increased mTORC1 activity is linked to the pathophysiology of epilepsy in both humans and animal models, and mTORC1 inhibition suppresses epileptogenesis in humans with tuberous sclerosis and animal models with elevated mTORC1 activity. However, the role of mTORC1-dependent translation and the neuronal cell types mediating the effect of enhanced mTORC1 activity in seizures remain unknown. The eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and 2 (4E-BP2) are translational repressors downstream of mTORC1. Here we show that the ablation of 4E-BP2, but not 4E-BP1, in mice increases the sensitivity to pentylenetetrazole (PTZ)- and kainic acid (KA)–induced seizures. We demonstrate that the deletion of 4E-BP2 in inhibitory, but not excitatory neurons, causes an increase in the susceptibility to PTZ-induced seizures. Moreover, mice lacking 4E-BP2 in parvalbumin, but not somatostatin or VIP inhibitory neurons exhibit a lowered threshold for seizure induction and reduced number of parvalbumin neurons. A mouse model harboring a human PIK3CA mutation that enhances the activity of the PI3K-AKT pathway (Pik3caH1047R-Pvalb) selectively in parvalbumin neurons shows susceptibility to PTZ-induced seizures. Our data identify 4E-BP2 as a regulator of epileptogenesis and highlight the central role of increased mTORC1-dependent translation in parvalbumin neurons in the pathophysiology of epilepsy.