Miracle-dz/UniFAR-FTUs huggingface dataset:
mOTUs: Profiling Taxonomic Composition, Transcriptional Activity and Strain Populations of Microbial Communities

The mOTU profiler, or mOTUs for short, is a software tool that enables the profiling of microbial communities in terms of their taxonomic composition, relative abundance of metabolically active members, and diversity of strain populations. To this end, it maintains a database of single‐copy phylogenetic marker gene sequences, which are used as a reference to which short read metagenomic and metatranscriptomic reads are mapped for the identification and quantification of microbial taxa. Here, we describe the most common use cases of the mOTU profiler in two basic protocols. Additional supporting protocols provide information on its installation and in‐depth guidance on adjusting its settings for increasing or decreasing the stringency with which taxa are detected and quantified, as well as for customizing the output file format. Guidelines for understanding the profiling results are provided, along with additional information on unique features, methodological details, and the development history of the tool. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.
Comparing Environmental Risk Regulations in China and the United States

The relative stringency of risk regulation across countries may have significant implications for public health and environmental outcomes, as well as for economic and trade impacts. In this study, we build on prior literature—which has often employed qualitative case studies, and has often focused on comparing the United States and Europe—by using a quantitative evidential reasoning approach to compare the relative stringency of federal/central level written rules for 45 randomly selected environmental risks in the United States and China. We find that, on average, in this sample of 45 environmental risks, the written rules for environmental risk regulation were more stringent in the United States than in China. Within this sample, we find that relative stringency was selective, leaning in both directions, as the United States and China each regulated some risks more stringently than the other; for example, the US written rules were more stringent for risks of toxic chemicals and most air pollutants, whereas China's written rules were more stringent for risks in agriculture. We also observe nuanced differences in relative regulatory stringency within sectors and risks; even where one country regulated one risk more stringently, the other country may regulate certain aspects of that risk more stringently. We comment on possible explanations for the patterns we observe. Our methods and findings may contribute to better understanding of comparative risk regulation across the United States and China, and worldwide. We also recognize that in addition to the written rules studied here, countries may also vary in their implementation.
Evidence of intergenerational transmission of diethylstilbestrol health effects: hindsight and insight

Abstract This review summarizes key findings from the US National Cancer Institute (NCI) diethylstilbestrol (DES) Combined Cohort Study with a focus on the results of the NCI Third Generation Study, a cohort of DES-exposed and -unexposed granddaughters. Findings to date from the Third Generation Study are discussed in the context of other research efforts and case reports, suggesting an intergenerational heritability of DES-related effects. The DES story serves as a model for the influence of endocrine disrupting chemicals on human health. It also serves as a warning of the special hazards of pregnancy exposures, and more broadly, of the potential for invisible health consequences arising from new or changing exposures. Summary sentence Diethylstilbestrol is associated with adverse health outcomes in women exposed during pregnancy and in prenatally exposed offspring, particularly daughters; evidence suggests that exposure health effects may extend to the next generation.
Abdominal Complications During Treatment for Pediatric Acute Myeloid Leukemia

Acute myeloid leukemia (AML) accounts for 15% to 20% of childhood leukemias. Because of high-intensive therapy, up to 5% of patients suffer from treatment-related mortality (TRM). Abdominal complications are frequent, however, literature on this subject is sparse. We aimed to characterize severe abdominal pain (AP) and hyperbilirubinemia experienced by pediatric AML patients treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML 2004 protocol (n=313). Patients were censored at hematopoietic stem cell transplantation and relapse. Toxicity information was collected prospectively. Additional information was requested retrospectively from the treating centers. Sixteen episodes of hyperbilirubinemia and 107 episodes of AP were reported. The treating centers deemed infection (30%) and typhlitis (18%) as the most frequent causes of AP. Six patients developed appendicitis (2%). Patients experiencing concurrent AP and sepsis had a high risk of TRM (36%, n=4). Eighty percent of episodes with hyperbilirubinemia fulfilled the European Society for Bone and Marrow Transplantation criteria for sinusoidal obstruction syndrome. In conclusion, abdominal complications were frequent with infection considered the predominate cause. Most patients with hyperbilirubinemia fulfilled the criteria for sinusoidal obstruction syndrome. AML treatment might be associated with appendicitis. Patients suffering from concurrent AP and sepsis had a high risk of TRM indicating that high awareness of abdominal complications is essential to reduce mortality, especially during sepsis.
Buprenorphine management in the perioperative period: educational review and recommendations from a multisociety expert panel

Background The past two decades have witnessed an epidemic of opioid use disorder (OUD) in the USA, resulting in catastrophic loss of life secondary to opioid overdoses. Medication treatment of opioid use disorder (MOUD) is effective, yet barriers to care continue to result in a large proportion of untreated individuals. Optimal analgesia can be obtained in patients with MOUD within the perioperative period. Anesthesiologists and pain physicians can recommend and consider initiating MOUD in patients with suspected OUD at the point of care; this can serve as a bridge to comprehensive treatment and ultimately save lives. Methods The Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, American Society of Anesthesiologists, American Academy of Pain Medicine, American Society of Addiction Medicine and American Society of Health System Pharmacists approved the creation of a Multisociety Working Group on Opioid Use Disorder, representing the fields of pain medicine, addiction, and pharmacy health sciences. An extensive literature search was performed by members of the working group. Multiple study types were included and reviewed for quality. A modified Delphi process was used to assess the literature and expert opinion for each topic, with 100% consensus being achieved on the statements and each recommendation. The consensus statements were then graded by the committee members using the United States Preventive Services Task Force grading of evidence guidelines. In addition to the consensus recommendations, a narrative overview of buprenorphine, including pharmacology and legal statutes, was performed. Results Two core topics were identified for the development of recommendations with >75% consensus as the goal for consensus; however, the working group achieved 100% consensus on both topics. Specific topics included (1) providing recommendations to aid physicians in the management of patients receiving buprenorphine for MOUD in the perioperative setting and (2) providing recommendations to aid physicians in the initiation of buprenorphine in patients with suspected OUD in the perioperative setting. Conclusions To decrease the risk of OUD recurrence, buprenorphine should not be routinely discontinued in the perioperative setting. Buprenorphine can be initiated in untreated patients with OUD and acute pain in the perioperative setting to decrease the risk of opioid recurrence and death from overdose.
YAP‐TEAD mediates PPAR α–induced hepatomegaly and liver regeneration in mice

Peroxisome proliferator–activated receptor α (PPARα, NR1C1) is a ligand‐activated nuclear receptor involved in the regulation of lipid catabolism and energy homeostasis. PPARα activation induces hepatomegaly and plays an important role in liver regeneration, but the underlying mechanisms remain unclear.
Sexual dimorphism in liver cell cycle and senescence signalling pathways in young and old rats

At the molecular level, cellular ageing involves changes in multiple gene pathways. Cellular senescence is both an important initiator and a consequence of natural ageing. Senescence results in changes in multiple cellular mechanisms that result in a natural decrease in cell cycle activity. Liver senescence changes impair hepatic function. Given the well‐established sexual dimorphism in ageing, we hypothesized that the natural hepatic ageing process is driven by sex‐dependent gene mechanisms. We studied our well‐characterized normal, chow‐fed rat ageing model, lifespan ∼850 days, in which we have reported ageing of metabolism, reproduction and endocrine function. We performed liver RNA‐seq on males and females at 110 and 650 days to determine changes in the cell cycle and cellular senescence signalling pathways. We found that natural liver ageing shows sexual dimorphism in these pathways. RNA‐seq revealed more male (3967) than female (283) differentially expressed genes between 110 and 650 days. Cell cycle pathway signalling changes in males showed decreased protein and expression of key genes (Cdk2, Cdk4, Cycd and PCNA) and increased expression ofp57 at 650 vs 110 days. In females, protein and gene expression of cell growth regulators, e.g. p15 and p21, which inhibit cell cycle G1 progression, were increased. The cell senescence pathway also showed sexual dimorphism. Igfbp3, mTOR and p62 gene and protein expression decreased in males while those ofTgfb3 increased in females. Understanding the involvement of cell cycling and cellular senescence pathways in natural ageing will advance evaluation of mechanisms associated with altered ageing and frailty trajectories.
Non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy is associated with lower cell-associated HIV RNA and DNA levels compared to protease inhibitor-based therapy

Background: It remains unclear whether combination antiretroviral therapy (ART) regimens differ in their ability to fully suppress human immunodeficiency virus (HIV) replication. Here, we report the results of two cross-sectional studies that compared levels of cell-associated (CA) HIV markers between individuals receiving suppressive ART containing either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Methods: CA HIV unspliced RNA and total HIV DNA were quantified in two cohorts (n = 100, n = 124) of individuals treated with triple ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an NNRTI or a PI. To compare CA HIV RNA and DNA levels between the regimens, we built multivariable models adjusting for age, gender, current and nadir CD4+ count, plasma viral load zenith, duration of virological suppression, NRTI backbone composition, low-level plasma HIV RNA detectability, and electronically measured adherence to ART. Results: In both cohorts, levels of CA HIV RNA and DNA strongly correlated (rho = 0.70 and rho = 0.54) and both markers were lower in NNRTI-treated than in PI-treated individuals. In the multivariable analysis, CA RNA in both cohorts remained significantly reduced in NNRTI-treated individuals (padj = 0.02 in both cohorts), with a similar but weaker association between the ART regimen and total HIV DNA (padj = 0.048 and padj = 0.10). No differences in CA HIV RNA or DNA levels were observed between individual NNRTIs or individual PIs, but CA HIV RNA was lower in individuals treated with either nevirapine or efavirenz, compared to PI-treated individuals. Conclusions: All current classes of antiretroviral drugs only prevent infection of new cells but do not inhibit HIV RNA transcription in long-lived reservoir cells. Therefore, these differences in CA HIV RNA and DNA levels by treatment regimen suggest that NNRTIs are more potent in suppressing HIV residual replication than PIs, which may result in a smaller viral reservoir size. Funding: This work was supported by ZonMw (09120011910035) and FP7 Health (305522).
Is the Genetic Code Optimized for Resource Conservation?

Abstract The causes and consequences of the nonrandom structure of the standard genetic code (SGC) have been of long-standing interest. A recent study reported that mutations in present-day protein-coding sequences are less likely to increase proteomic nitrogen and carbon uses under the SGC than under random genetic codes, concluding that the SGC has been selectively optimized for resource conservation. If true, this finding might offer important information on the environment in which the SGC and some of the earliest life forms evolved. However, we here show that the hypothesis of optimization of a genetic code for resource conservation is theoretically untenable. We discover that the aforementioned study estimated the expected mutational effect by inappropriately excluding mutations lowering resource consumptions and including mutations involving stop codons. After remedying these problems, we find no evidence that the SGC is optimized for nitrogen or carbon conservation.
A Roadmap to Implementing Venous Thromboembolism Risk Stratification and Mitigation

Supplemental digital content is available in the text. Introduction Venous thromboembolism (VTE) is a life-threatening postoperative complication that carries high morbidity and mortality for plastic surgery patients. In 2011, the American Society of Plastic Surgeons recommended the adoption of a VTE risk stratification and mitigation; however, successful implementation of VTE prophylaxis protocols has not been well described. To address and reduce the VTE burden at our academic center, a risk assessment protocol was implemented for patients undergoing outpatient plastic surgery procedures. Method All patients who received outpatient plastic surgery between August 2018 and July 2019 were eligible for the VTE modified Caprini risk assessment screening. Sampling of practice patterns was done by chart review from the first week of each month. The study was divided into 3 phases to assess the relationship of screening compliance rates with each protocol change. Compliance was defined as completion of VTE Caprini screening with documentation in patients' charts. Results Over the 12-month study period, 277 patients met the inclusion criteria. From August to November 2018 (phase 1), patients were screened at the initial clinic visit with an average compliance rate of 11.1%. In December 2018 (phase 2), patients were screened on the day of surgery, with an average compliance rate of 47.1%. From January to July 2019 (phase 3), surgeons recorded the numerical Caprini score into the patient's electronic medical record with a subsequent compliance rate of 61.3%. The overall compliance during the 12 months was 44.8%. The median calculated Caprini score for this population was 4 (range, 1–7). Conclusions Standardization of VTE risk assessment is vital for patient safety and outcomes. Successful implementation and long-term protocol sustainability are not a simple goal. In this study, protocol compliance greatly improved after tailoring the guidelines to the specific institutional needs and workflow. These results reinforce the importance of continuous protocol review and modification to ensure optimal departmental buy-in and sustainability.
Multiple thrombotic sources and embolic events at arterial sites in a patient with protein-C deficiency

Protein-C deficiency causes a thrombophilic environment in circulation. Although venous thromboembolism is the most common presentation, arterial events are rare. A 45 year-old woman with protein-C deficiency presented with multiple thromboembolic events including bilateral renal infarct and inferior ST-elevation myocardial infarction 3-days after coronary angiography via femoral approach which were normal coronary arteries. Computed tomographic angiography and transesophageal echocardioraphy displayed multiple thrombi sources including left atrium, left subclavian artery, sinus valsalva and descending aorta. Unfractionated-heparin and tissue plasminogen activator infusion were given. Although regression in ST-segment elevation and chest pain, no reduction in sizes of left atrial and aortic thrombus was observed by imaging modality. The patient refused surgical removal of thrombi, then warfarin therapy was planned. In patients with congenital thrombophilia and history of thromboembolism, anticoagulant treatment should be carefully managed during percutaneous diagnostic and interventional treatments and they should be performed by radial approach without interruption of anticoagulants.
The effect of national disease-modifying therapy subsidy policy on long-term disability outcomes in people with multiple sclerosis

Background: Disease-modifying therapies (DMTs) are used to treat people with relapsing-onset multiple sclerosis (ROMS), but our knowledge is largely limited to their short-term effects. Objective: To determine (1) the impact of national-level DMT subsidy policy on DMT use and health outcomes in people with MS (PwMS) and (2) the long-term effects of DMT on disability and quality of life (QoL; 5-level EQ-5D version (EQ-5D-5L) utility value). Methods: This observational cohort study compared Australian and New Zealand populations with different levels of DMT availability 10–20 years post-ROMS diagnosis. Between-country differences were assessed using standardised differences. Associations were assessed with multivariable linear regression models. Results: We recruited 328 Australians and 256 New Zealanders. The Australian cohort had longer DMT treatment duration, greater proportion of disease course treated and shorter duration between diagnosis and starting DMT. The Australian cohort had lower median Expanded Disability Status Scale (EDSS) (3.5 vs 4.0) and Multiple Sclerosis Severity Score (MSSS) (3.05 vs 3.71) and higher QoL (0.71 vs 0.65). In multivariable models, between-country differences in disability and QoL were largely attributed to differential use of DMT. Conclusions: This study provides evidence for the impact of national-level DMT policy on disability outcomes in PwMS. Where DMTs are more accessible, PwMS experienced less disability progression and improved QoL 10–20 years post-diagnosis.
Factors associated with early and late digital revascularization and replantation failure: a retrospective cohort study

Factors associated with failure of digital revascularization and replantation procedures have been well characterized, but studies have not investigated failures occurring beyond the early postoperative period. A single-centre retrospective chart review included 284 patients (434 digits) who underwent digital revascularization or replantation. Patient-, injury- and surgery-related characteristics were compared among successful procedures, digits that failed while in hospital (early failure), and initially viable digits that failed after hospital discharge (late failure). Overall, 202 patients had successful procedures (71%). There were 51 early failures (18%) and 31 late failures (11%). Crush injuries and vein grafting were associated with early failure only. Complete amputations and leeching were strongly associated with both early and late failure. This study revealed that a substantial proportion of initially viable digits fail after discharge from hospital. Patients with signs of venous congestion may benefit from longer observation periods in hospital to avoid late failure. Level of evidence: IV
Cognitive and Executive Contributions to Trail-Making Task Performance on Adolescents With and Without Attention Deficit Hyperactivity Disorder

Objective: The trail making task is used to assess executive functioning in ADHD youth, yet has only been validated in adult populations. We compare the relative contributions of various cognitive measures to performance on a trail making task analog, the Switching of Attention (SoA) task, in typically-developing and ADHD adolescents. Method: Participants were 160 adolescents with ADHD from the International Study to Predict Optimized Treatment—in ADHD, assessed at pretreatment baseline and 6-week medicated follow-up, and 160 matched typically-developing peers. Attention, processing speed, working memory, impulsivity, and motor speed were assessed using a cognitive battery. Results: Processing speed and working memory significantly contributed to SoA performance in ADHD, regardless of medication status. While medicated, motor speed also underpinned the prediction of most task measures. For typically-developing adolescents, sustained attention and working memory contributed to SoA performance. Conclusion: Typically-developing, unmedicated and treated ADHD adolescents recruit different aspects of cognition during SoA completion.
Systematic review of health-related quality of life following thyroid cancer

This systematic review provides a summary of all studies published between 2000 and 2019 using a health-related quality of life (HRQOL) patient-completed questionnaire to report outcomes following diagnosis and treatment of thyroid cancer. The search terms were “thyroid cancer” or “thyroid carcinoma,” “quality of life” or “health related quality of life,” and “questionnaire” or “patient reported outcome. ” EMBASE, PubMed, Medline, PsycINFO, CINAHL, and HaNDLE-On-QOL search engines were searched between 2 February and 23 February 2020. A total of 811 identified articles were reduced to 314 when duplicates were removed. After exclusion criteria (not thyroid specific, no quality of life questionnaires, and conference abstracts) were applied, 92 remained. Hand searching identified a further 2 articles. Of the 94 included, 16 had a surgical, 26 a primarily medical, and 52 a general focus. There were articles from 27 countries. A total of 49 articles were published from 2015 through 2019 inclusive. A total of 72 questionnaires were used among the articles and a range of 7 to 2215 participants were included within each article. This review demonstrated an increasing number of publications annually. The scope of enquiry into aspects of HRQOL following thyroid cancer is broad, with relatively few addressing surgical aspects and many focusing on the impact of radio-iodine. More research is required into shared decision-making in initial management decisions and HRQOL and interventions aimed specifically at addressing long-term HRQOL difficulties.