Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of Ocular Muscles in Patients With Myasthenia Gravis With Nonocular Onset

Background: Myasthenia gravis (MG) is an autoimmune disorder involving neuromuscular junctions and more than half of MG patients manifested with extraocular muscle weakness initially. In the remained patients, ocular weakness may occur later in the course of the disease. However, little data are available about ocular involvement in such patients. Therefore, the study aims to investigate ocular weakness in MG patients with nonocular onset and evaluate the associated factors influencing it. Methods: In our monocentric retrospective study, 54 adult-onset patients with MG with nonocular onset were included and were followed up for at least 2 years from the onset. The primary outcome was the occurrence of ptosis, diplopia, or both. Kaplan–Meier analysis was performed to estimate the time to the ocular weakness, and log-rank tests were used to analyze the association between clinical characteristics and ocular weakness. Multivariate Cox proportional hazards regression models were used to identify factors associated with ocular involvement. Results: A total of 47 (87.0%) patients developed ocular weakness during the study period. The median time to ocular weakness was 6.0 months. Time to the ocular involvement was earlier in patients with bulbar onset (P = 0.007), whereas patients receiving pyridostigmine monotherapy and immunomodulatory therapy had a longer median time of ocular weakness (P < 0.0001). No significant difference was noted between ocular weakness and age of onset, gender, and thymoma. The Cox analysis showed that bulbar onset was a risk factor of ocular weakness (adjusted hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.41–4.99), whereas pyridostigmine monotherapy (adjusted HR 0.28, 95% CI 0.13–0.60) and immunotherapy (adjusted HR 0.09, 95% CI 0.04–0.22) were protective factors. Conclusions: Eighty-seven percent of patients with MG with nonocular onset developed ocular weakness. Bulbar onset was an independent risk factor for ocular involvement, whereas pyridostigmine and immunotherapy were protective factors.
Models of Inflammation: Carrageenan Air Pouch

The subcutaneous air pouch is an in vivo model that can be used to study the components of acute and chronic inflammation, the resolution of the inflammatory response, the oxidative stress response, and potential therapeutic targets for treating inflammation. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this article has been extensively used to identify potential anti‐inflammatory drugs. © 2021 Wiley Periodicals LLC.
Long-Term Hydromethylthionine Treatment Is Associated with Delayed Clinical Onset and Slowing of Cerebral Atrophy in a Pre-Symptomatic P301S MAPT Mutation Carrier

One of the mutations in the microtubule-associated protein tau, P301S, is causative for dominantly inherited frontotemporal dementia characterized by extensive tau pathology for which no licensed treatment is available. Hydromethylthionine is a potent tau aggregation inhibitor. We report treatment of an asymptomatic carrier of the P301S mutation using hydromethylthionine over a 5-year period beginning at the mean age of onset of clinical decline in the family. During the period of treatment, the rates of progression of cerebral atrophy were reduced by 61%–66% in frontal and temporal lobes, and the patient remained clinically asymptomatic.
Synergistic antimicrobial activities of epigallocatechin gallate, myricetin, daidzein, gallic acid, epicatechin, 3‐hydroxy‐6‐methoxyflavone and genistein combined with antibiotics against ESKAPE pathogens

To verify synergistic effects, we investigated the antimicrobial activity of seven phenolic phytochemicals (gallic acid; epicatechin; epigallocatechin gallate; daidzein; genistein; myricetin; 3‐hydroxy‐6‐methoxyflavone) in combination with six antibiotics against multidrug‐resistant isolates from the ESKAPE group.
The Response and Tolerability of a Novel Cold Atmospheric Plasma Wound Dressing for the Healing of Split Skin Graft Donor Sites: A Controlled Pilot Study

Introduction: Cold atmospheric plasma (CAP) has positive effects on wound healing and antimicrobial properties. However, an ongoing challenge is the development of specific modes of application for different clinical indications. Objectives: We investigated in a prospective pilot study the response and tolerability of a newly developed CAP wound dressing for the acute healing of split skin graft donor sites compared to conventional therapy. Methods: We applied both treatments to each patient (n = 10) for 7 days and measured 4 parameters of wound healing every other day (i.e., 1,440 measurements) using a hyperspectral imaging camera. Additionally, we evaluated the clinical appearance and pain levels reported by the patients. Results: The CAP wound dressing was superior to the control (p < 0.001) in the improvement of 3 wound parameters, that is, deep tissue oxygen saturation, hemoglobin distribution, and tissue water distribution. CAP was well tolerated, and pain levels were lower in CAP-treated wound areas. Conclusion: CAP wound dressing is a promising new tool for acute wound healing.
Single‐Cell RNA‐Seq of T Cells in B‐ALL Patients Reveals an Exhausted Subset with Remarkable Heterogeneity

Characterization of functional T cell clusters is key to developing strategies for immunotherapy and predicting clinical responses in leukemia. Here, single‐cell RNA sequencing is performed with T cells sorted from the peripheral blood of healthy individuals and patients with B cell‐acute lymphoblastic leukemia (B‐ALL). Unbiased bioinformatics analysis enabled the authors to identify 13 T cell clusters in the patients based on their molecular properties. All 11 major T cell subsets in healthy individuals are found in the patients with B‐ALL, with the counterparts in the patients universally showing more activated characteristics. Two exhausted T cell populations, characterized by up‐regulation of TIGIT, PDCD1, HLADRA, LAG3, and CTLA4 are specifically discovered in B‐ALL patients. Of note, these exhausted T cells possess remarkable heterogeneity, and ten sub‐clusters are further identified, which are characterized by different cell cycle phases, naïve states, and GNLY (coding granulysin) expression. Coupled with single‐cell T cell receptor repertoire profiling, diverse originations of the exhausted T cells in B‐ALL are suggested, and clonally expanded exhausted T cells are likely to originate from CD8+ effector memory/terminal effector cells. Together, these data provide for the first‐time valuable insights for understanding exhausted T cell populations in leukemia.
The feasibility of withdrawing canakinumab in paediatric colchicine-resistant familial Mediterranean fever patients.

OBJECTIVES To determine the feasibility of withdrawing canakinumab (CAN) in a large cohort of paediatric patients with colchicine-resistant familial Mediterranean fever (crFMF). METHODS This retrospective observational cohort study included paediatric crFMF patients that received CAN treatment for ≥6 months. Patient data were recorded at treatment onset (baseline), and at 1, 3, 6, 12, 18, and 24 months after initiation of treatment. RESULTS The study included 114 patients that were followed-up for 2736 person-months. During the 24-month follow-up period, the CAN dose interval remained unchanged in 44 patients. The dose interval was extended in 58 patients within a median 6 months (range: 3-18 months) of treatment initiation. In all, 4 of these 58 patients had a new attack of crFMF after the dose interval was extended. CAN was withdrawn in 12 patients (in 5 at month 12 month and in 7 at month 18), of which 2 had a new attack within 3 months of withdrawal. In these 2 patients CAN was re-initiated with a dose interval of 8 weeks. The remaining 10 patients in which CAN was withdrawn did not report any symptoms throughout the remainder of the 24-month follow-up period. The median attack-free period in those treated with CAN was 669 d (95% CI: 644-696). CONCLUSIONS The present findings show that it may be feasible to withdraw CAN or extend its dose interval in paediatric crFMF patients. Based on the present findings, we think that as the quantity of real-life data increases, standard CAN protocols may be developed.
Social capital, perceived neighborhood environment, and depressive symptoms among older adults in rural China: the role of self-rated health

ABSTRACT Objectives: This study examined the relationships between social capital, perceived neighborhood environment, and depressive symptoms among older adults living in rural China, and the moderating effect of self-rated health (SRH) in these relationships. Participants: A quota sampling method was applied to recruit 447 participants aged 60 years and older in rural communities in Jilin province, China in 2019. Measurements: Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale. Structural equation modeling was used to build latent constructs of social capital and test the proposed model. Multiple group analysis was used to test the moderation effects. Results: Cognitive social capital and structural social capital were both associated with depressive symptoms controlling for participants’ demographics, socioeconomic status, and health status. After adding perceived environment variables in the model, the relationship between cognitive social capital and depressive symptoms became nonsignificant, while structural social capital remained became a significant factor (β = −.168, p < .01). Satisfaction with health care was significantly associated with depressive symptoms among those with poor SRH (β = −.272, p < .01), whereas satisfaction with security and transportation were strongly associated with depressive symptoms among those with good SRH (security: β = −.148, p < .01; transportation: β = −.174, p < .01). Conclusions: Study findings highlighted the importance of social capital and neighborhood environment as potential protective factors of depressive symptoms in later life. Policy and intervention implications were also discussed.
Tumor-to-Tumor Metastasis: Lung Adenocarcinoma as a Recipient of Metastasis from Renal Cell Carcinoma: A Case Report

Patient: Male, 67-year-old Final Diagnosis: Lung adenocarcinoma Symptoms: Abdominal pain Medication:— Clinical Procedure: Lobectomy Specialty: Oncology • Pathology Objective: Rare co-existance of disease or pathology Background: The occurrence of metastasis from one neoplasm to another is known as tumor-to-tumor metastasis (TTM). It is a rare phenomenon in the natural history of any neoplasm, with approximately 100 cases reported in the literature to date. The lungs are the most frequent metastatic tumor donors and kidney cancer is the most common recipient. However, the opposite phenomenon (lung adenocarcinoma as a recipient of metastasis from renal carcinoma) has not been previously reported in the literature. Case Report: We present the case of a man with a history of multiple neoplasms. He had a diffuse large B-cell lymphoma in 2006, a left papillary renal cell carcinoma (RCC) type 2 in 2006, and an acinar adenocarcinoma of the prostate in 2011. A follow-up computed tomography scan in July 2019 showed a suspicious lung nodule on the left upper lobe and a retroperitoneal hypermetabolic mass on the positron emission tomography scan. The lung nodule and retroperitoneal mass biopsies were consistent with a primary lung adenocarcinoma with a lepidic pattern and a metastatic RCC, respectively. In January 2020, he underwent a thoracoscopic left upper lobectomy and a mediastinal lymph node dissection. Histopathological evaluation revealed a 2-cm nodule composed of a lung adenocarcinoma with an intratumoral metastasis from a papillary RCC. To date, the patient has stable renal neoplastic metastatic disease and no locoregional recurrences of the lung adenocarcinoma. Conclusions: Metastasis from one primary tumor to another primary tumor is an extremely unusual event. We report one of the first cases of an RCC metastasis to a primary lung adenocarcinoma.
CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming

Neuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs eventually develop resistance to RA. Loss of the chromatin modifier chromatin assembly factor 1 subunit p150 (CHAF1A) promotes NB cell differentiation; however, the mechanism by which CHAF1A drives NB oncogenesis has remained unexplored. This study shows that CHAF1A gain‐of‐function supports cell malignancy, blocks neuronal differentiation in three models (zebrafish NC, human NC, and human NB), and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression. Targeting polyamine synthesis promotes NB differentiation and enhances the anti‐tumor activity of RA. The authors' results provide insight into the mechanisms that drive NB oncogenesis and suggest a rapidly translatable therapeutic approach (DFMO plus RA) to enhance the clinical efficacy of differentiation therapy in NB patients.
Thiostrepton inhibits growth and induces apoptosis by targeting FoxM1/SKP2/MTH1 axis in B-precursor acute lymphoblastic leukemia cells

Abstract Forkhead box M1 (FoxM1) is a transcription factor that plays an important role in the etiology of many cancers, however, its role has not been elucidated in B-precursor acute lymphoblastic leukemia (B-pre-ALL). In the current study, we showed that the downregulation of FoxM1 by its inhibitor thiostrepton inhibited cell viability and induced caspase-dependent apoptosis in a panel of B-pre-ALL cell lines. Thiostrepton led downregulation of FoxM1 accompanied by decreased expression of Aurora kinase A, B, matrix metalloproteinases, and oncogene SKP2 as well as MTH1. Downregulation of the FoxM1/SKP2/MTH1 axis led to increase in the Bax/Bcl2 ratio and suppression of antiapoptotic proteins. Thiostrepton-mediated apoptosis was prevented by N-acetyl cysteine, a scavenger of reactive oxygen species. Co-treatment of B-pre-ALL with subtoxic doses of thiostrepton and bortezomib potentiated the proapoptotic action. Altogether, our results suggest that targeting FoxM1expression could be an attractive strategy for the treatment of B-pre-ALL.
Well-Being of Health Care Professionals Treating Opioid Use Disorder During the COVID-19 Pandemic: Results From a National Survey.

OBJECTIVE The COVID-19 pandemic has dramatically affected health care delivery, effects that are juxtaposed with health care professional (HCP) burnout and mental distress. The Opioid Use Disorder Provider COVID-19 Survey was conducted to better understand the impact of COVID-19 on clinical practice and HCP well-being. METHODS The cross-sectional survey was e-mailed to listservs with approximately 157,000 subscribers of diverse professions between July 14 and August 15, 2020. Two dependent variables evaluated HCP functioning and work-life balance. Independent variables assessed organizational practices and HCP experiences. Covariates included participant demographic characteristics, addiction board certification, and practice setting. Multilevel multivariate logistic regression models were used. RESULTS Among 812 survey respondents, most were men, White, and physicians, with 46% located in urban settings. Function-impairing anxiety was reported by 17%, and 28% reported more difficulty with work-life balance. Difficulty with functioning was positively associated with having staff who were sick with COVID-19 and feeling close to patients, and was negatively associated with being male and having no staff changes. Difficulty with work-life balance was positively associated with addiction board certification; working in multiple settings; having layoffs, furloughs, or reduced hours; staff illness with COVID-19; and group well-being check-ins. It was negatively associated with male gender, older age, and no staff changes. CONCLUSIONS Demographic, provider, and organizational-practice variables were associated with reporting negative measures of well-being during the COVID-19 pandemic. These results should inform HCPs and their organizations on factors that may lead to burnout, with particular focus on gender and age-related concerns and the role of well-being check-ins.
COVID-19 Vaccine Hesitancy Among Community-Dwelling Older Adults: The Role of Information Sources

Despite high enthusiasm surrounding the rollout of the COVID-19 vaccine, some older adults continue to remain hesitant about its receipt. There is limited evidence on vaccine hesitancy among community-dwelling older adults. In this study, we examine the prevalence and predictors (particularly the role played by information sources) of vaccine hesitancy in this group. We use the Medicare Current Beneficiary Survey and employ multivariable logistic regression models to explore this. Relative to those relying on regular news, those depending on health care providers (HCPs), social media, other internet/webpages, and family/friends as the main information source on COVID-19 expressed higher negative vaccine intent. The high negative intent with HCPs as the main information source should be interpreted with caution. This could be reflective of the timing of the survey and changing attitude toward the vaccine among HCPs themselves.
Text neck: An adverse postural phenomenon.

BACKGROUND The excessive use of hand-held mobile devices (HHMD) leads to a postural phenomenon known as text neck. OBJECTIVE The aim of this paper is to discuss the anatomical, biomechanical and muscle activation changes within the cervical and thoracic regions associated with the sustained, forward, flexed neck posture, observed with excessive usage of hand-held mobile devices. Additionally, this paper examines the relationship of gender, as well as the effects of carrying backpack loads by youth, on this forward, flexed neck posture. METHODS Multiple aspects of the text neck position that occur when an individual uses a HHMD are described. RESULTS Prolonged use of hand-held mobile devices results in adverse anatomical and biomechanical changes in the cervical and thoracic spine, muscular imbalances, and postural compensations, all of which contribute to muscular overuse and fatigue resulting in pain. CONCLUSIONS Physical therapists must educate their patients about proper posture while using hand-held mobile devices. Proper posture includes: holding the device close to eye level, using the device while standing or sitting and holding the device with a line of sight perpendicular to the surface of the device, using a larger screen, and texting with both hands. Also, because children are using hand held mobile devices at younger ages, parents and teachers must be educated about the dangers of prolonged use of hand-held devices.
Droplet digital polymerase chain reaction for detection and quantification of cell-free DNA TP53 target somatic mutations in oral cancer

BACKGROUND: TP53 mutation is a driver mutation of oral carcinogenesis. This study investigated cancerous and cell-free DNA (cfDNA) in patients with oral squamous cell carcinoma (OSCC) to detect the target hotspot somatic mutation of TP53. OBJECTIVE: TP53 target hotspot mutations were determined in surgically resected primary tumor samples from 107 OSCC patients. METHODS: Cancerous and cfDNA samples were examined for mutations through droplet digital polymerase chain reaction (ddPCR) by using mutation-specific assays. The ddPCR results were evaluated alongside clinicopathological data. RESULTS: In total, 23 cases had target TP53 mutations in varying degrees. We found that OSCC had relatively low cfDNA shedding, and mutations were at low allele frequencies. Of these 23 cases, 13 had target TP53 mutations in their corresponding cfDNA. Target somatic mutations in cancerous DNA and cfDNA are related to cervical lymph node metastasis. The cfDNA concentration is related to primary tumor size, lymph node metastasis, and OSCC stage. CONCLUSIONS: Our results show that the detection of TP53 target somatic mutations in OSCC patients by using ddPCR is technically feasible. Low levels of cfDNA may produce different results between cancerous tissue and cfDNA analyses. Future research on cfDNA may quantify diagnostic biomarkers in the surveillance of OSCC patients.
Justifications for heavy alcohol use among gender and sexually diverse people

ABSTRACT A range of research reports that many gender and sexually diverse people drink alcohol at heavy levels. This study used 24 focus groups to explore shared understandings of alcohol use among gender and sexually diverse people living in New Zealand. An inductive, data-driven thematic analysis was employed to identify explanations for heavy drinking among gender and sexually diverse people. Three key explanations were articulated: alcohol is needed for socialising; drinking helps coping with stress; alcohol and drug treatment services are inadequate. These results demonstrate justifications for heavy drinking in certain contexts. This behaviour runs counter to public health approaches and messages that highlight low-risk levels of drinking or not drinking as desirable. Public health interventions should continue to address alcohol use at a whole population level but should be supplemented by policy and interventions that take into account the sociocultural contexts and structural conditions that encourage drinking among gender and sexually diverse people.
Cell competition in intratumoral and tumor microenvironment interactions

Tumors are complex cellular and acellular environments within which cancer clones are under continuous selection pressures. Cancer cells are in a permanent mode of interaction and competition with each other as well as with the immediate microenvironment. In the course of these competitive interactions, cells share information regarding their general state of fitness, with less‐fit cells being typically eliminated via apoptosis at the hands of those cells with greater cellular fitness. Competitive interactions involving exchange of cell fitness information have implications for tumor growth, metastasis, and therapy outcomes. Recent research has highlighted sophisticated pathways such as Flower, Hippo, Myc, and p53 signaling, which are employed by cancer cells and the surrounding microenvironment cells to achieve their evolutionary goals by means of cell competition mechanisms. In this review, we discuss these recent findings and explain their importance and role in evolution, growth, and treatment of cancer. We further consider potential physiological conditions, such as hypoxia and chemotherapy, that can function as selective pressures under which cell competition mechanisms may evolve differently or synergistically to confer oncogenic advantages to cancer.