Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of resident memory CD8+ T cells with functional specificity for SARS-CoV-2 in unexposed oropharyngeal lymphoid tissue

Description Tissue-resident memory CD8+ T cells in unexposed oropharyngeal lymphoid tissue exhibit specificity for SARS-CoV-2. Preexisting T cell immunity to SARS-CoV-2 Preexisting immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been previously identified, because SARS-CoV-2–specific CD4+ T cells can be found in the blood of unexposed individuals. However, the presence of preexisting T cells that recognize SARS-CoV-2 in unexposed individuals has not been identified in oropharyngeal tissues. Here, Niessl et al. took tonsil samples from children and adults prepandemic and found the presence of SARS-CoV-2–specific CD4+ and CD8+ T cells. SARS-CoV-2–specific CD8+ T cells were more readily detected in the tonsils compared with the blood and displayed a resident memory phenotype but were less functional than CD8+ T cells specific for other viruses. Thus, this work suggests that there is tonsil-resident, preexisting T cell memory in some people who have not been exposed to SARS-CoV-2. Cross-reactive CD4+ T cells that recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more commonly detected in the peripheral blood of unexposed individuals compared with SARS-CoV-2–reactive CD8+ T cells. However, large numbers of memory CD8+ T cells reside in tissues, feasibly harboring localized SARS-CoV-2–specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virus-specific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19 (coronavirus disease 2019). We found that SARS-CoV-2–specific memory CD4+ T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2–specific memory CD8+ T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2–specific memory CD8+ T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus–specific memory CD8+ T cells, but were functionally less potent than other virus-specific memory CD8+ T cell responses. The presence of preexisting tissue-resident memory CD8+ T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.
Positive Feedback Regulation of fzd7 Expression Robustly Shapes Wnt Signaling Range in Early Heart Development

Secreted molecules called morphogens govern tissue patterning in a concentration-dependent manner. However, it is still unclear how reproducible patterning can be achieved with diffusing molecules, especially when patterning differentiation of a thin region. Wnt is a morphogen that organizes cardiac development; especially Wnt6 patterns the cardiogenic mesoderm to induce differentiation of a thin pericardium in Xenopus. It is, however, unclear how Wnt6 can pattern such a thin tissue. In this study, we reveal that a Wnt receptor, frizzled7, is expressed in a Wnt-dependent manner in the prospective heart region, and that this receptor-feedback is essential for shaping a steep gradient of Wnt. In addition, the feedback imparts robustness against fluctuations of Wnt ligand production and allows the system to reach a steady state quickly. We also found a Wnt antagonist sFRP1, which is expressed at the opposite side of Wnt source, accumulates on a novel type of heparan sulfate (HS), N-acetyl-rich HS, which is highly presented in the outer of cardiogenic mesoderm, achieving local inhibition of Wnt signaling by restricting sFRP1 spreading. These two intricate regulatory systems restrict Wnt signaling and ensure reproducible patterning of a thin pericardium tissue.
Inhibition of TGF‐β Increases Bone Volume and Strength in a Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI), is a genetic disorder of bone fragility caused by mutations in collagen I or proteins involved in collagen processing. Previous studies in mice and human OI bones have shown that excessive activation of TGF‐β signaling plays an important role in dominant and recessive OI disease progression. Inhibition of TGF‐β signaling with a murine pan‐specific TGF‐β neutralizing antibody (1D11) was shown to significantly increase trabecular bone volume and long bone strength in mouse models of OI. To investigate the frequency of dosing and dose options of TGF‐β neutralizing antibody therapy, we assessed the effect of 1D11 on disease progression in a dominant OI mouse model (col1a2 gene mutation at G610C). In comparison with OI mice treated with a control antibody, we attempted to define mechanistic effects of 1D11 measured via μCT, biomechanical, dynamic histomorphometry, and serum biomarkers of bone turnover. In addition, osteoblast and osteoclast numbers in histological bone sections were assessed to better understand the mechanism of action of the 1D11 antibody in OI. Here we show that 1D11 treatment resulted in both dose and frequency dependency, increases in trabecular bone volume fraction and ultimate force in lumbar bone, and ultimate force, bending strength, yield force, and yield strength in the femur (p ≤ 0.05). Suppression of serum biomarkers of osteoblast differentiation, osteocalcin, resorption, CTx‐1, and bone formation were observed after 1D11 treatment of OI mice. Immunohistochemical analysis showed dose and frequency dependent decreases in runt‐related transcription factor, and increase in alkaline phosphatase in lumbar bone sections. In addition, a significant decrease in TRACP and the number of osteoclasts to bone surface area was observed with 1D11 treatment. Our results show that inhibition of the TGF‐β pathway corrects the high‐turnover aspects of bone disease and improves biomechanical properties of OI mice. These results highlight the potential for a novel treatment for osteogenesis imperfecta. © 2021 Sanofi‐Genzyme. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Impact of COVID-19 on patient health and self-care practices: a mixed-methods survey with German patients

Objective This study aimed to examine German patients’: (1) self-estimation of the impact of the pandemic on their health and healthcare; and (2) use of digital self-care practices during the pandemic. Design Cross-sectional mixed-methods survey. Setting and participants General practice patients from four physicians’ offices located in urban and rural areas of Bavaria, Germany, between 21 July 2020 and 17 October 2020. A total of 254 patients participated (55% response rate); 57% (262 of 459) identified as female and participants had an average age of 39.3 years. Patients were eligible to participate if they were 18 years or older and spoke German, and had access to the internet. Results (1) Healthcare for patients was affected by the pandemic, and the mental health of a small group of respondents was particularly affected. The risk of depression and anxiety disorder was significantly increased in patients with quarantine experience. (2) Self-care practices have increased; more than one-third (39%) of participants indicated that they started a new or additional self-care practice during the pandemic, and about a quarter (23%) of patients who were not previously engaged in self-care practices started new self-care activities for the first time; however, such practices were not necessarily digital. Conclusions Further investigation is required to understand the relationship between digital self-care and public health events such as the COVID-19 pandemic, and to develop strategies to alleviate the burden of the quarantine experience for patients.
Mapping the digital food environment: A systematic scoping review

Food environments are directly linked to diets and health outcomes such as overweight, obesity, and noncommunicable diseases. The digitalization of food environments is becoming a central issue in public health, yet little is known about this emerging field. We performed a systematic scoping review to map the research on the digital food environment and investigate how the eight dimensions of the food environment, according to an established framework (availability, prices, vendor and product properties, marketing and regulation, accessibility, affordability, convenience, and desirability), might be shifting in the context of a digital society. We searched MEDLINE, EMBASE, Scopus, and Web of Science for studies published between 2000 and 2019, using search terms covering digital technology and food environment, which yielded 13,580 unique records. Our analysis of 357 studies shows that digitalization is taking place in all dimensions of the food environment, and enabling the emergence of new forms of buying and selling food, such as online grocery shopping and online food delivery, which may be changing availability of foods and affecting the physical distance to shops and time allocated for shopping. Systematic reviews identified indicated that digital food marketing and social media can influence food choices, preferences and consumption. Our findings suggest that digital and physical food environments are interconnected and influencing one another, but the impact of the digital on health and nutrition is yet unclear.
Marker-assisted Selection of New Compounds in Moringa oleifera Lam. Induced by Gamma Irradiation

THE DRY seeds of the medicinal plant Moringa oleifera were exposed to four gamma rays doses (0, 20, 40 and 60Gy) using 60Co gamma unit (Indian gamma cell), that delivered 2.25kGy per hour. Gas chromatography-mass spectrometry (GC-MS) analysis was performed to identify the chemical profile of the ethanol extracts of non-irradiated and gamma irradiated (20, 40 and 60Gy) leaf samples of Moringa oleifera. New chemical compounds such as 5-hydroxymethylfurfural (5-HMF) and 2, 3-dihydro-3, 5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) were detected in the irradiated samples. Ten start codon-targeted (SCoT) primers were used to detect markers correlated with the appearance of 5-HMF and DDMP. Twenty four markers have been used for assessing the new compounds at the three radiation doses used. Nine of them represented positive markers that appeared in the plants treated with each of the three doses under study (20, 40 and 60Gy), but they were absent in the corresponding control. On the other hand, fifteen bands represented negative markers that appeared in non-irradiated samples and were absent in the irradiated ones. The primer SCoT 5 showed the highest percentage of polymorphism (83.3%).
Catch the tweet to fight the flu: Using Twitter to promote flu shots on a college campus

Abstract Objective: Over the 2018–2019 flu season we conducted a randomized controlled trial examining the efficacy of a Twitter campaign on vaccination rates. Concurrently we investigated potential interactions between digital social network structure and vaccination status. Participants: Undergratuates at a large midwestern public university were randomly assigned to an intervention (n = 353) or control (n = 349) group. Methods: Vaccination data were collected via monthly surveys. Participant Twitter data were collected through the public-facing Twitter API. Intervention impact was assessed with logistic regression. Standard network science tools examined vaccination coverage over online social networks. Results: The campaign had no effect on vaccination outcome. Receiving a flu shot the prior year had a positive impact on participant vaccination. Evidence of an interaction between digital social network structure and vaccination status was detected. Conclusions: Social media campaigns may not be sufficient for increasing vaccination rates. There may be potential for social media campaigns that leverage network structure.
Phase Ib Dose Expansion and Translational Analyses of Olaparib in Combination with Capivasertib in Recurrent Endometrial, Triple-Negative Breast, and Ovarian Cancer

Purpose: On the basis of strong preclinical rationale, we sought to confirm recommended phase II dose (RP2D) for olaparib, a PARP inhibitor, combined with the AKT inhibitor capivasertib and assess molecular markers of response and resistance. Patients and Methods: We performed a safety lead-in followed by expansion in endometrial, triple-negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300 mg orally twice daily and capivasertib orally twice daily on a 4-day on 3-day off schedule was evaluated. Two dose levels (DL) of capivasertib were planned: 400 mg (DL1) and 320 mg (DL-1). Patients underwent biopsies at baseline and 28 days. Results: A total of 38 patients were enrolled. Seven (18%) had germline BRCA1/2 mutations. The first 2 patients on DL1 experienced dose-limiting toxicities (DLT) of diarrhea and vomiting. No DLTs were observed on DL-1 (n = 6); therefore, DL1 was reexplored (n = 6) with no DLTs, confirming DL1 as RP2D. Most common treatment-related grade 3/4 adverse events were anemia (23.7%) and leukopenia (10.5%). Of 32 evaluable subjects, 6 (19%) had partial response (PR); PR rate was 44.4% in endometrial cancer. Seven (22%) additional patients had stable disease greater than 4 months. Tumor analysis demonstrated strong correlations between response and immune activity, cell-cycle alterations, and DNA damage response. Therapy resistance was associated with receptor tyrosine kinase and RAS-MAPK pathway activity, metabolism, and epigenetics. Conclusions: The combination of olaparib and capivasertib is associated to no serious adverse events and demonstrates durable activity in ovarian, endometrial, and breast cancers, with promising responses in endometrial cancer. Importantly, tumor samples acquired pre- and on-therapy can help predict patient benefit.
Science funding under an authoritarian regime: Portugal's National Education Board and the European ‘academic landscape’ in the interwar period

This article enables an understanding of scientific practice and funding in a peripheral country ruled by a dictatorship in the interwar period, and thus provides the basis for comparison with studies of other non-democratic regimes. We examine the work of Portugal's Junta de Educação Nacional (National Education Board), which administered and provided funding for science from 1929 to 1936. Our findings show that this public body encouraged the participation of the Portuguese academic community in international science networks. This scenario contrasts with the dominant historiographical thesis that between the wars the Portuguese academic community did not play a role in international networks, and that it lacked state support. Also in contrast with the dominant historiography, whose ideological bias meant that a simplified picture was portrayed, whereas the reality is shown to be complex, this study demonstrates that the Portuguese dictatorial state sought to foster scientific progress through the Junta, but that resentment among academics and the resistance of universities to innovation meant that this objective was only partially achieved. Finally, the memory of a number of scientists has been rescued from oblivion, as we show how their political stance during the dictatorship led to their being ignored by historiographers when democracy prevailed.
The Identification and Genetic Characterization of Parechovirus Infection Among Pediatric Patients With Wide Clinical Spectrum in Chongqing, China

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34–0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23–4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It’s concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.
Mitochondrial DNA sequencing of a wet-collection syntype demonstrates the importance of type material as genetic resource for lantern shark taxonomy (Chondrichthyes: Etmopteridae)

After initial detection of target archival DNA of a 116-year-old syntype specimen of the smooth lantern shark, Etmopterus pusillus, in a single-stranded DNA library, we shotgun-sequenced additional 9 million reads from this same DNA library. Sequencing reads were used for extracting mitochondrial sequence information for analyses of mitochondrial DNA characteristics and reconstruction of the mitochondrial genome. The archival DNA is highly fragmented. A total of 4599 mitochondrial reads were available for the genome reconstruction using an iterative mapping approach. The resulting genome sequence has 12 times coverage and a length of 16 741 bp. All 37 vertebrate mitochondrial loci plus the control region were identified and annotated. The mitochondrial NADH2 gene was subsequently used to place the syntype haplotype in a network comprising multiple E. pusillus samples from various distant localities as well as sequences from a morphological similar species, the shortfin smooth lantern shark Etmopterus joungi. Results confirm the almost global distribution of E. pusillus and suggest E. joungi to be a junior synonym of E. pusillus. As mitochondrial DNA often represents the only available reference information in non-model organisms, this study illustrates the importance of mitochondrial DNA from an aged, wet collection type specimen for taxonomy.
Do mechanisms matter? Comparing cancer treatment strategies across mathematical models and outcome objectives

When eradication is impossible, cancer treatment aims to delay the emergence of resistance while minimizing cancer burden and treatment. Adaptive therapies may achieve these aims, with success based on three assumptions: resistance is costly, sensitive cells compete with resistant cells, and therapy reduces the population of sensitive cells. We use a range of mathematical models and treatment strategies to investigate the tradeoff between controlling cell populations and delaying the emergence of resistance. These models extend game theoretic and competition models with four additional components: 1) an Allee effect where cell populations grow more slowly at low population sizes, 2) healthy cells that compete with cancer cells, 3) immune cells that suppress cancer cells, and 4) resource competition for a growth factor like androgen. In comparing maximum tolerable dose, intermittent treatment, and adaptive therapy strategies, no therapeutic choice robustly breaks the three-way tradeoff among the three therapeutic aims. Almost all models show a tight tradeoff between time to emergence of resistant cells and cancer cell burden, with intermittent and adaptive therapies following identical curves. For most models, some adaptive therapies delay overall tumor growth more than intermittent therapies, but at the cost of higher cell populations. The Allee effect breaks these relationships, with some adaptive therapies performing poorly due to their failure to treat sufficiently to drive populations below the threshold. When eradication is impossible, no treatment can simultaneously delay emergence of resistance, limit total cancer cell numbers, and minimize treatment. Simple mathematical models can play a role in designing the next generation of therapies that balance these competing objectives.
Lymphocyte‐to‐monocyte ratio is a predictor of clinically significant prostate cancer at prostate biopsy

Inflammation plays critical roles at different stages of carcinogenesis and cancer progression. Several previous studies showed conflicting results for the predictive role of systemic inflammation markers in the detection of clinically significant prostate cancers (CSPCs). We aimed to determine the predictive roles of lymphocyte‐to‐monocyte (LMR) and eosinophil‐to‐lymphocyte ratios (ELR) in the detection of CSPC at standard 12‐core transrectal ultrasound‐guided prostate biopsy (12‐core‐TRUS‐Bx) using our large‐cohort database.
Interdependence of a mechanosensitive anion channel and glutamate receptors in distal wound signaling

Glutamate has dual roles in metabolism and signaling; thus, signaling functions must be isolatable and distinct from metabolic fluctuations, as seen in low-glutamate domains at synapses. In plants, wounding triggers electrical and calcium (Ca2+) signaling, which involve homologs of mammalian glutamate receptors. The hydraulic dispersal and squeeze-cell hypotheses implicate pressure as a key component of systemic signaling. Here, we identify the stretch-activated anion channel MSL10 as necessary for proper wound-induced electrical and Ca2+ signaling. Wound gene induction, genetics, and Ca2+ imaging indicate that MSL10 acts in the same pathway as the glutamate receptor–like proteins (GLRs). Analogous to mammalian NMDA glutamate receptors, GLRs may serve as coincidence detectors gated by the combined requirement for ligand binding and membrane depolarization, here mediated by stretch activation of MSL10. This study provides a molecular genetic basis for a role of mechanical signal perception and the transmission of long-distance electrical and Ca2+ signals in plants.