Citations

AbstractOral cavity lymphomas constitute only 3% of all lymphomas in the general population but are the third most common oral malignancy. A 67‐year‐old female with a history of osteoporosis, Graves’ disease and non‐Hodgkin's lymphoma was referred to the Department of Dental Specialties with a chief complaint of persistent soft tissue swelling facial to the maxillary incisors of possible non‐odontogenic origin. To expedite care, the patient was first seen via teledentistry and subsequently appointed for an in‐person evaluation and treatment. Examination revealed 1–3 mm probing depths and a firm, non‐tender, non‐fluctuant mass in the facial soft tissues approximating teeth nos. 7–10. Biopsy of the affected area was performed. A diagnosis of recurrent follicle center cell lymphoma, a form of non‐Hodgkin's lymphoma, was rendered. The patient was subsequently referred to the Oncology and Hematology team, followed for 6 weeks and remained symptom‐free. This case underlies the importance of teledentistry to expedite care and manage patient expectations. Additionally, it also underscores the importance of microscopic examination of tissue samples from oral lesions that appear non‐odontogenic in nature and reinforces the role of dentistry in uncovering the oral‐systemic link.

AbstractAcute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID‐19) and is associated with in‐hospital death. We investigated the incidence of AKI in 223 hospitalized COVID‐19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID‐19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID‐19 and 99 with severe COVID‐19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID‐19 and 4.0% for moderate COVID‐19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150–8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361–13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622–22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 10⁹/L, interquartile range [IQR] 11.3 vs. 8.3 × 10⁹/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID‐19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID‐19 patients.

The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. The expansion properties of human hepatocytes in immunodeficient mice are well known. However, little has been reported about larger animals that are more scalable and practical for clinical purposes. Therefore, we engineered immunodeficient swine to support expansion of human hepatocytes and identify barriers to their clinical application. Immunodeficient swine were engineered by knockout of the recombinase-activating gene 2 ( RAG2 ) and fumarylacetoacetate hydrolase (FAH). Immature human hepatocytes (ihHCs) were injected into fetal swine by intrauterine cell transplantation (IUCT) at day 40 of gestation. Human albumin was measured as a marker of engraftment. Cytotoxicity against ihHCs was measured in transplanted piglets and control swine. We initially detected higher levels of human albumin in cord blood of newborn FAH/ RAG2 -deficient (FR) pigs compared with immunocompetent controls (196.26 ng/dL vs. 39.29 ng/dL, p = 0.008), indicating successful engraftment of ihHCs after IUCT and adaptive immunity in the fetus. Although rare hepatocytes staining positive for human albumin were observed, levels of human albumin did not rise after birth, but declined, suggesting rejection of xenografted ihHCs. Cytotoxicity against ihHCs increased after birth by 3.8% (95% CI: [2.1%–5.4%], p < 0.001) and inversely correlated with declining levels of human albumin ( p = 2.1 × 10 −5 , R 2 = 0.17). Circulating numbers of T cells and B cells were negligible in FR pigs. However, circulating natural killer (NK) cells exerted cytotoxicity against ihHCs. NK cell activity was lower in immunodeficient piglets after IUCT than in naive controls (30.4% vs. 40.1%, p = 0.011, 95% CI for difference [2.7%–16.7%]). In conclusion, ihHCs were successfully engrafted in FR swine after IUCT. NK cells were a significant barrier to expansion of hepatocytes. New approaches are needed to overcome this hurdle and allow large-scale expansion of human hepatocytes in immunodeficient swine. Impact statement There is currently a need for robust expansion of human hepatocytes. We describe an immunodeficient swine model into which we engrafted immature human hepatocytes (ihHCs). We identified the mechanism of the eventual graft rejection by the intact NK cell population, which has not been previously shown to have a significant role in xenograft rejection. By both improving engraftment and reducing NK cell-mediated cytotoxicity toward the graft through intrauterine cell transfer, we confirmed the presence of residual adaptive immunity in this model of immunodeficiency and the ability to induce hyposensitization in the NK cell population by taking advantage of the fetal microenvironment.

High-resolution esophageal manometry (HRM) is frequently used in the outpatient setting, but its role in the inpatient setting is unknown. We conducted a retrospective study of patients who underwent inpatient or outpatient HRM. Few differences were noted between groups and 28% of inpatients had an additional intervention. Tolerance of oral diet and diabetes were associated with a lower likelihood of additional intervention. Ultimately, the inpatient HRM group had unique characteristics and few subsequent interventions.

How to catch a dynamic state AMP-activated protein kinase (AMPK) is a key sensor of energy status in eukaryotes. Its dynamic structure is regulated by allosteric factors including phosphorylation and binding of nucleotides and metabolites. Yan et al. developed conformation-specific antibodies that trap AMPK in a fully inactive state that has experienced a large, domain-level rotation. Biophysical experiments in cells and in vitro are consistent with the structural work and support a model in which the activation loop is fully exposed in the completely inactive, dephosphorylated state. These structures inform our understanding of the complex allosteric behavior in this crucial metabolic regulator. Science , abe7565, this issue p. 413

Objectives To observe the weight change in Chinese youth during a 4-month COVID-19 lockdown, and the association between weight change and mental health, physical activity and sedentary time changes, and dietary habits. Design A retrospective observational study. Settings Two universities located in Zhejiang and Hunan provinces, China. Participants This study enrolled 12 889 college students whose body weight was measured before the lockdown (1 December 2019–20 January 2020) at the two universities, and reported their weight measured at home or community after the end of the lockdown (1–23 May 2020) via an online follow-up questionnaire. Primary and secondary outcome measures The primary outcome was the weight change in Chinese youth during a 4-month lockdown resulting from the COVID-19 pandemic. The secondary outcomes were the relationships of weight change to COVID-19-related stress, depression, anxiety, physical activity and sedentary time changes, and dietary habits. Results Participants’ ages ranged from 17 to 27 years ( M =19, SD=1) with 80.2% identified as female. The average absolute and relative changes in body weight were 2.6 (95% CI 2.0 to 3.2)) kg and 4.2% (95% CI 4.0% to 4.3%) for men, and 2.1 (1.9 to 2.4) kg and 4.2% (95% CI 3.9% to 4.4%) for women. An increase in overweight and obese individuals according to Asian cut-off points as a demographic percentage by 4.5% and 2.7% and 4.8% and 3.4% in men and women, respectively ( P <0.001), was observed. Weight gain was significantly associated with increased sedentary time and an increase in COVID-19-related stress and depression score. Conclusion The present study’s results suggest that the risk of weight gain in Chinese youth during the lockdown increased and that strategies to decrease sedentary time and improve mental health may be warranted to mitigate weight gain during and after the COVID-19 pandemic.

Abstract Cell fate conversion by overexpressing defined factors is a powerful tool in regenerative medicine. However, identifying key factors for cell fate conversion requires laborious experimental efforts; thus, many of such conversions have not been achieved yet. Nevertheless, cell fate conversions found in many published studies were incomplete as the expression of important gene sets could not be manipulated thoroughly. Therefore, the identification of master transcription factors for complete and efficient conversion is crucial to render this technology more applicable clinically. In the past decade, systematic analyses on various single-cell and bulk OMICs data have uncovered numerous gene regulatory mechanisms, and made it possible to predict master gene regulators during cell fate conversion. By virtue of the sparse structure of master transcription factors and the group structure of their simultaneous regulatory effects on the cell fate conversion process, this study introduces a novel computational method predicting master transcription factors based on group sparse optimization technique integrating data from multi-OMICs levels, which can be applicable to both single-cell and bulk OMICs data with a high tolerance of data sparsity. When it is compared with current prediction methods by cross-referencing published and validated master transcription factors, it possesses superior performance. In short, this method facilitates fast identification of key regulators, give raise to the possibility of higher successful conversion rate and in the hope of reducing experimental cost.