Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting autotaxin impacts disease advance in the SOD1‐G93A mouse model of amyotrophic lateral sclerosis

A preclinical strategy to broaden the search of potentially effective treatments in amyotrophic lateral sclerosis (ALS) relies on identifying factors controlling motor neuron (MN) excitability. These partners might be part of still unknown pathogenic pathways and/or useful for the design of new interventions to affect disease progression. In this framework, the bioactive membrane‐derived phospholipid lysophosphatidic acid (LPA) affects MN excitability through LPA receptor 1 (LPA1). Furthermore, LPA1 knockdown is neuroprotective in transgenic ALS SOD1‐G93A mice. On this basis, we raised the hypothesis that the major LPA‐synthesizing ectoenzyme, autotaxin (ATX), regulates MN excitability and is a potential target to modulate disease development in ALS mice. We show here that PF‐8380, a specific ATX inhibitor, reduced intrinsic membrane excitability (IME) of hypoglossal MNs in brainstem slices, supporting that baseline ATX activity regulates MN IME. PF‐8380‐induced alterations were prevented by a small‐interfering RNA directed against mRNA for lpa1. These outcomes support that impact of ATX‐originated lysophospholipids on MN IME engages, at least, the G‐protein‐coupled receptor LPA1. Interestingly, mRNAatx levels increased in the spinal cord of pre‐symptomatic (1–2 months old) SOD1‐G93A mice, thus preceding MN loss. The rise in transcripts levels also occurred in cultured spinal cord MNs from SOD1‐G93A embryos, suggesting that mRNAatx upregulation in MNs is an etiopathogenic event in the ALS cell model. Remarkably, chronic administration in the drinking water of the orally bioavailable ATX inhibitor PF‐8380 delayed MN loss, motor deterioration and prolonged life span in ALS mice. Treatment also led to a reduction in LPA1‐immunoreactive patches in transgenic animals mostly in MNs. These outcomes support that neuroprotective effects of interfering with ATX in SOD1‐G93A mice rely, at least in part, on LPA1 knockdown in MNs. Therefore, we propose ATX as a potential target and/or a biomarker in ALS and highlight ATX inhibitors as reasonable tools with therapeutic usefulness for this lethal pathology.
Comparison of flow cytometry and next‐generation sequencing in minimal residual disease monitoring of acute myeloid leukemia: One institute’s practical clinical experience

Monitoring patients with acute myeloid leukemia can be implemented through various techniques such as multiparameter flow cytometry, real‐time quantitative polymerase chain reaction, and next‐generation sequencing. However, there is scarce studies when comparing the data of next‐generation sequencing and flow cytometry for monitoring disease progression, particularly how they might supplement one another when used in tandem.
Citizen Science Provides an Efficient Method for Broad-Scale Tick-Borne Pathogen Surveillance of Ixodes pacificus and Ixodes scapularis across the United States

In the 21st century, zoonotic pathogens continue to emerge, while previously discovered pathogens continue to have changes within their distribution and prevalence. Monitoring these pathogens is resource intensive, requiring both field and laboratory support; thus, data sets are often limited within their spatial and temporal extents. ABSTRACT Tick-borne diseases have expanded over the last 2 decades as a result of shifts in tick and pathogen distributions. These shifts have significantly increased the need for accurate portrayal of real-time pathogen distributions and prevalence in hopes of stemming increases in human morbidity. Traditionally, pathogen distribution and prevalence have been monitored through case reports or scientific collections of ticks or reservoir hosts, both of which have challenges that impact the extent, availability, and accuracy of these data. Citizen science tick collections and testing campaigns supplement these data and provide timely estimates of pathogen prevalence and distributions to help characterize and understand tick-borne disease threats to communities. We utilized our national citizen science tick collection and testing program to describe the distribution and prevalence of four Ixodes-borne pathogens, Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Anaplasma phagocytophilum, and Babesia microti, across the continental United States. IMPORTANCE In the 21st century, zoonotic pathogens continue to emerge, while previously discovered pathogens continue to have changes within their distribution and prevalence. Monitoring these pathogens is resource intensive, requiring both field and laboratory support; thus, data sets are often limited within their spatial and temporal extents. Citizen science collections provide a method to harness the general public to collect samples, enabling real-time monitoring of pathogen distribution and prevalence.
Prevalence and factors associated with sepsis and septic shock in oncological patients in intensive therapy.

OBJECTIVES to analyze factors associated with sepsis and septic shock in cancer patients in the Intensive Care Unit. METHODS cross-sectional, retrospective study with a quantitative approach, with a sample of 239 patients in an oncology hospital. Secondary data from medical records were used. The outcome variable was "presence of sepsis and/or septic shock"; and exposures: sex, length of stay, origin, use of invasive procedures and primary tumor site. Descriptive, bivariate analyzes and multiple logistic regression models were performed. RESULTS the prevalence of sepsis was 95% CI: 14.7-24.7 and septic shock of 95% CI: 37.7-50.3. In the multiple analysis, sepsis and/or septic shock were associated with hospital stay longer than seven days, being from the Emergency Department, presence of invasive procedures and hematological site. CONCLUSIONS sepsis and/or septic shock in cancer patients were associated with clinical characteristics and health care factors.
Therapeutic education as a tool to improve patient‐reported and clinical outcomes after renal transplantation: results of the EPHEGREN multicenter retrospective cohort study

Patients are not always aware of the inconveniences associated with renal transplantation, which they compare with a « rebirth », and from which they expect complete recovery. Therapeutic education is proposed to prepare patients for their life after transplantation. This study evaluated the impact of pretransplant therapeutic education on patient‐reported outcomes and rejection‐free survival over the first year. We collected data from 383 renal transplant patients followed‐up in seven centers. Patients who benefited from therapeutic education before transplantation (N = 182) were compared with patients who did not (N = 139) for quality‐of‐life, adherence and adverse events using the Pearson’s chi‐square test, one‐way ANOVA or t‐test. The association between therapeutic education and time to acute rejection was investigated using Cox models. The patients who benefited from therapeutic education reported adverse events less frequently (e.g., tremor: 9% vs. 32.4%, P = 0.01) and better quality‐of‐life (MCS‐QOL: 50.7 ± 8.1 vs. 47.7 ± 9.5, P = 0.02; PCS‐QOL: 49.1 ± 7.1 vs. 46.0 ± 9.2, P = 0.013). No difference was found on adherence. Rejection‐free survival was slightly better in the therapeutic education group (HR = 0.44, 95% CI = [0.19–1.01]). This multicenter retrospective cohort study suggests that integrating therapeutic education to care pathways entails clinical benefit, in terms of quality‐of‐life, self‐reported adverse events and rejection‐free survival. Randomized clinical trials are necessary to confirm this.
COVID shelter in place orders and mental health outcomes among college undergraduates

Abstract Objective The purpose of this study is to examine the relationship , if any, COVID-19 shelter-in-place orders had on mental health outcomes for undergraduate students. Participants This study was comprised of 138 students, all of which were recruited from a single four-year college in the Midwest. Methods A pre-/post-test comparative design was adopted and was leveraged to capture data regarding students’ experiences before and after the shelter-in-place orders were enacted to determine if there was a marked effect between the pre-virus condition and the situation after stay at home orders went into effect. Results Paired sample t-test were conducted to determine whether the mental health outcomes of depression, anxiety and stress were significantly changed from before to after COVID-19 shelter in place disorders. While anxiety and stress scores were revealed no significant difference, significantly greater depression was revealed after COVID-19. Conclusion Overall, the results of this study highlight the need for colleges to be aware of the mental health toll that the pandemic and shelter-in-place orders may take on their students. Though this toll registered only directly in depression, there remains significant reasons to believe the situation may also affect stress and anxiety regardless of the absence of evidence for these factors in this study. There remains much to be done in assessing the ultimate impact of the pandemic on students’ mental health.
Causes of death in HIV-infected and HIV-uninfected children aged under-five years in western Kenya

Supplemental Digital Content is available in the text Objectives: Describe the causes of death among infants and children less than 5 years stratified by HIV status. Design: Cross-sectional analysis of causes of death ascertained through minimally invasive tissue sampling (MITS) in the Kenya Child Health and Mortality Prevention Surveillance site. Methods: We included decedents aged 28 days to less than 5 years, whose death was reported within 36 h, underwent MITS, and had HIV test results and causes of death determined. MITS specimens were tested using Taqman Array Cards, culture, cytology, histopathology and immunohistochemistry and HIV PCR. A panel evaluated epidemiologic, clinical, verbal autopsy and laboratory data to assign causes of death using ICD-10 guidelines. Causes of death and etiological agents were stratified by HIV status. Results: Of 176 included decedents, 14% (n = 25) were HIV-infected, median viral load was 112 205 copies/ml [interquartile range (IQR) = 9349–2 670 143). HIV-disease (96%; n = 24) and malnutrition (23%; n = 34) were the leading underlying causes of death in HIV-infected and HIV-uninfected decedents, respectively. Malnutrition was more frequent in the causal chain of HIV-infected (56%; n = 14) than HIV-uninfected decedents (31%; n = 49) (P value = 0.03). Viral pneumonia was twice as common in HIV-infected (50%; n = 9) than HIV-uninfected decedents (22%; n = 7) (P value = 0.04). Conclusion: Nearly all HIV-infected decedents’ underlying cause of death was HIV disease, which was associated with malnutrition. Our findings underscore the need for strengthening early identification and management of HIV-infected children. Prevention, early diagnosis and treatment of malnutrition could be instrumental in improving the survival of HIV-infected and HIV-uninfected children.
Whole-genome assembly of Ganoderma leucocontextum (Ganodermataceae, Fungi) discovered from the Tibetan Plateau of China

Abstract Ganoderma leucocontextum, a newly discovered species of Ganodermataceae in China, has diverse pharmacological activities. Ganoderma leucocontextum was widely cultivated in southwest China, but the systematic genetic study has been impeded by the lack of a reference genome. Herein, we present the first whole-genome assembly of G. leucocontextum based on the Illumina and Nanopore platform from high-quality DNA extracted from a monokaryon strain (DH-8). The generated genome was 50.05 Mb in size with an N50 scaffold size of 3.06 Mb, 78,206 coding sequences, and 13,390 putative genes. Genome completeness was assessed using the Benchmarking Universal Single-Copy Orthologs (BUSCO) tool, which identified 96.55% of the 280 Fungi BUSCO genes. Furthermore, differences in functional genes of secondary metabolites (terpenoids) were analyzed between G. leucocontextum and Ganoderma lucidum. Ganoderma leucocontextum has more genes related to terpenoids synthesis compared to G. lucidum, which may be one of the reasons why they exhibit different biological activities. This is the first genome assembly and annotation for G. leucocontextum, which would enrich the toolbox for biological and genetic studies in G. leucocontextum.
Advancement in Arthroscopic Superior Capsular Reconstruction for Irreparable Massive Rotator Cuff Tear

Irreparable massive rotator cuff tear (IMRCT) was one of the causes of shoulder dysfunction, despite technical improvement, the failure rate of IMRCT was still demonstrated to be high. Traditional treatments like non‐surgical treatments, partial rotator cuff repair, and tendon transfers could only achieve a slight improvement. A potential cause for high failure rate was the fact that traditional treatments cannot restore the superior stability of glenohumeral joint, and thus restricted the movement of shoulder joint severely. Superior capsular reconstruction (SCR) using a variety of grafts (autograft, allograft, xenograft, or synthetic grafts) provided a promising option for IMRCT. In surgery, graft was fixed medially to superior glenoid and laterally to the footprint of humeral greater tuberosity. SCR could increase the stability of the superior glenohumeral joint, decrease the subacromial pressure and acromiohumeral distance. This review summarized the relevant literature regarding the alternative grafts, surgery indications, operative techniques and clinical outcomes of SCR. we compared the different grafts, key surgical steps, the advantages and disadvantages of different surgical methods to provide clinicians with new surgical insights into the treatments of IMRCT. In conclusion, IMRCT without severe glenohumeral arthritis was the best suitable indication for SCR. The clinical outcomes were positive in the short‐term and middle‐term following‐up. More studies were necessary to determine long‐term results of this surgical procedure.
Immunogenicity and safety of different schedules of the meningococcal ABCWY vaccine, with assessment of long-term antibody persistence and booster responses – results from two phase 2b randomized trials in adolescents

ABSTRACT The meningococcal serogroup B (MenB) protein vaccine, 4CMenB, combined with MenA, MenC, MenW and MenY polysaccharide-protein conjugates for a pentavalent MenABCWY vaccine, can potentially protect against most causative agents of invasive meningococcal disease worldwide. Two phase 2b, randomized, multicenter studies were conducted (NCT02212457, NCT02946385) to assess the immunogenicity and safety of the MenABCWY vaccine as well as antibody persistence and response to a booster dose 2 years after the last vaccination, compared to 4CMenB vaccination. Participants (10 − 18 years), randomized (3:3:2:2:2:2), received the 4-component 4CMenB vaccine according to a 0–2 month (M) schedule or MenABCWY according to a 0–2, 0–6, 0-2-6, 0–1, or 0–11 M schedule. All participants received 5 injections (at M0, M1, M2, M6 and M12) with either the study vaccines or placebo/hepatitis A vaccine. Follow-on participants (4CMenB-0-2, MenABCWY-0-2, MenABCWY-0-6 and MenABCWY-0-2-6 groups) received one dose of either 4CMenB (4CMenB-0-2 group) or MenABCWY and newly enrolled, age-matched, meningococcal vaccine-naïve adolescents (randomized 1:1) received 2 doses (0–2 M) of either 4CMenB or MenABCWY. MenABCWY vaccination was immunogenic against MenB test strains. Non-inferiority for all 4 components of the 4CMenB vaccine could not be demonstrated for the 0–2 M schedule. Antibodies persisted up to 2 years post-MenABCWY vaccination and a booster dose induced an anamnestic response as higher titers were observed in follow-on participants compared to the first-dose response in vaccine-naïve participants. MenABCWY had a clinically-acceptable safety profile, not different from that of 4CMenB.
Perceived social stigma, self-concealment, and suicide risk among North Korean refugee women exposed to traumatic events.

INTRODUCTION Suicide among North Korean (NK) refugee women is one of the most concerning public health problems in South Korea. Pre-resettlement trauma exposure and post-resettlement factors can contribute to suicide risk among NK refugee women; however, few studies have explored these associations. METHODS This study aimed to assess suicidal ideation and suicide attempts among NK refugee women in South Korea (N = 212) and to examine the impact of pre-resettlement trauma exposure on suicide risk. Perceived social stigma and self-concealment in the post-resettlement phases were investigated as moderating factors for suicide risk related to trauma exposure using multiple regression analyses. RESULTS Trauma exposure significantly increased suicidal ideation severity and the risk of suicide attempt. Furthermore, perceived social stigma significantly moderated this relationship such that the impact of trauma exposure in the pre-resettlement phases was amplified as perceived social stigma increased. CONCLUSION Based on our study findings, professionals working with refugee populations should assess for perceived social stigma and exposure to traumatic events to reduce and prevent suicidal ideation and attempts.
Evaluation and treatment of facial feminization surgery: part I. forehead, orbits, eyebrows, eyes, and nose

Facial feminization surgery (FFS) incorporates aesthetic and craniofacial surgical principles and techniques to feminize masculine facial features and facilitate gender transitioning. A detailed understanding of the defining male and female facial characteristics is essential for success. In this first part of a two-part series, we discuss key aspects of the general preoperative consultation that should be considered when evaluating the prospective facial feminization patient. Assessment of the forehead, orbits, hairline, eyebrows, eyes, and nose and the associated procedures, including scalp advancement, supraorbital rim reduction, setback of the anterior table of the frontal sinus, rhinoplasty, and soft tissue modifications of the upper and midface are discussed. In the second part of this series, bony manipulation of the midface, mandible, and chin, as well as soft tissue modification of the nasolabial complex and chondrolaryngoplasty are discussed. Finally, a review of the literature on patient-reported outcomes in this population following FFS is provided.
Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke.

Importance Understanding the temporal association between atrial fibrillation (AF) and ischemic stroke informs our understanding of the AF-stroke mechanism and treatment of paroxysmal AF. Objective To define the temporal association between episodes of AF and stroke in patients with cardiac implantable electronic devices (CIEDs). Design, Setting, and Participants In this case-crossover study, data from a large national electronic health record database were linked with a single-vendor database of heart rhythm records of patients with CIEDs capable of continuous heart rhythm monitoring. Patients with CIEDs who sustained an ischemic stroke who also had 120 days of continuous remote rhythm monitoring prestroke were included. Data were collected from January 2007 to March 2017, and data were analyzed from November 2019 to June 2020. Exposure AF for 5.5 hours or more on any given day during days 1 to 30 vs days 91 to 120 prestroke. Main Outcomes and Measures Odds ratio for stroke comparing AF during days 1 to 30 vs 91 to 120 prestroke. This analysis was planned prior to the study. Results From 466 635 patients included in both the Optum electronic health record and CareLink databases, 891 patients with CIEDs and ischemic stroke with continuous monitoring in the 120 days prestroke were identified. Of 891 included patients, 575 (64.5%) were male, and the median (interquartile range) age was 76 (67-82) years. The vast majority of patients with stroke had either no AF meeting the threshold duration of 5.5 hours or more in both the case and control periods (682 of 891 [76.5%]) or AF of 5.5 hours or more in both periods (143 of 891 [16.0%]). For those not meeting the 5.5-hour AF threshold in either period, there was no or very little AF throughout the 120 days prestroke. A total of 66 patients had informative, discordant arrhythmic states, with 52 having AF of 5.5 hours or more in the case period vs 14 in the control period (odds ratio [OR], 3.71; 95% CI, 2.06-6.70). Stroke risk was increased most in days 1 to 5 following an AF episode (OR, 5.00; 95% CI, 2.62-9.55). AF greater than 23 hours on a given day was associated with the clearest increase in stroke risk (OR, 5.00; 95% CI, 2.08-12.01). Conclusions and Relevance In this large cohort of patients with CIEDs and continuous rhythm monitoring prior to ischemic stroke, excess stroke risk above baseline was highest within 5 days of an episode of AF of 5.5 hours or more in duration and diminished rapidly thereafter. Our findings are consistent with the traditional view that AF is directly and transiently associated with ischemic stroke. These results provide support for trials of time-delimited anticoagulation for patients with infrequent multihour episodes of AF and rigorous, continuous rhythm monitoring.
Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial

Objectives: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. Methods: Patients aged 18–70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0–2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). Results: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. Conclusions: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.