Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of a Lighted Stent by Near-Infrared Observation to Identify the Urethra During Transanal Total Mesorectal Excision.

256 DISEASES OF THE COLON & RECTUM VOLUME 63: 2 (2020) Transanal total mesorectal excision (taTME) is a new and complex technique that may improve the quality of total mesorectal excision for patients with mid and low rectal cancer. However, it has been established that there is a risk of iatrogenic urethral injury in men undergoing this technique. A registry reported urethral injury at a rate of 0.8% (12/1594). According to single-center published series, the frequency of urethral injury with taTME has been reported to range from 0% to 6.7%. The use of a lighted stent has been reported as a method to visualize the urethra to prevent urethral injury. In the past, the lighted stent was barely visible under normal-intensity laparoscopic light conditions. Therefore, to identify the urethra clearly, it was necessary to change laparoscopic light to the turned-off condition. However, the surrounding tissue cannot be visualized with the laparoscopic light turned off. Laparoscopic near-infrared observation may therefore be useful for solving this problem. In this video article, we demonstrate the use of a lighted infrared stent (Infrared Illumination System, Stryker, Inc, Kalamazoo, MI) by near-infrared observation to identify the urethra during taTME. The lighted stent can be detected as a strong green fluorescent signal using laparoscopic near-infrared light. This method makes the urethra more clearly translucent and identifiable than previous usage without losing visibility of the surrounding tissue during taTME. See Video at http://links.lww. com/ DCR/B13.
Dynamic and regulated TAF gene expression during mouse embryonic germ cell development

Germ cells undergo many developmental transitions before ultimately becoming either eggs or sperm, and during embryonic development these transitions include epigenetic reprogramming, quiescence, and meiosis. To begin understanding the transcriptional regulation underlying these complex processes, we examined the spatial and temporal expression of TAF4b, a variant TFIID subunit required for fertility, during embryonic germ cell development. By analyzing published datasets and using our own experimental system to validate these expression studies, we determined that both Taf4b mRNA and protein are highly germ cell-enriched and that Taf4b mRNA levels dramatically increase from embryonic day 12.5–18.5. Surprisingly, additional mRNAs encoding other TFIID subunits are coordinately upregulated through this time course, including Taf7l and Taf9b. The expression of several of these germ cell-enriched TFIID genes is dependent upon Dazl and/or Stra8, known regulators of germ cell development and meiosis. Together, these data suggest that germ cells employ a highly specialized and dynamic form of TFIID to drive the transcriptional programs that underlie mammalian germ cell development.
We need an operational framework for heterogeneity in psychiatric research

Despite advancements in research methods and the growth of large international data sharing initiatives,1 our understanding of the biological underpinnings of psychiatric disorders remains limited. An often cited reason for this stagnation is the presence of “heterogeneity,” whether intrinsic to the condition or an artifact of clinical assessment, sampling, experimental protocol, or otherwise. However, for a concept of such longstanding importance to psychiatric research, we have no consistent framework within which to study heterogeneity itself. In this editorial, we argue that heterogeneity must be under stood and communicated in 2 ways. First, we must have a sense of what heterogeneity is as a mathematical and statistical concept. In this respect, we highlight that heterogeneity is generally viewed as a combination of deviance (the degree of differences between elements in a set) and multimodality (the number of clusters in a set or modes in a mixture distribution), both of which can be expressed in a common and easily interpretable set of units known as the “numbers equivalent” or “effective numbers. ”2,3 Second, we must understand that the conceptual relevance of heterogeneity is linked to where (in terms of levels of analysis) it is expressed. That is, heterogeneity gains substantial conceptual power only when discussed with specific reference to the space of features being deemed heterogeneous. Here, too, we argue that the units of numbers equivalent can clarify the level at which heterogeneity is being discussed. A central emphasis of this argument, overall, is that understanding heterogeneity requires us to separate our understanding of it as a quantity from the conditions and features that we deem to be heterogeneous, and the causes thereof.
First-Ever Ischemic Stroke and Incident Major Adverse Cardiovascular Events in 93 627 Older Women and Men

Supplemental Digital Content is available in the text. Background and Purpose— Stroke risk is sex-specific, but little is known about sex differences of poststroke major adverse cardiovascular events (MACEs). Stroke-related brain damage causes autonomic dysfunction and inflammation, sometimes resulting in cardiac complications. Sex-specific cardiovascular susceptibility to stroke without the confounding effect of preexisting heart disease constitutes an unexplored field because previous studies focusing on sex differences in poststroke MACE have not excluded patients with known cardiovascular comorbidities. We therefore investigated sex-specific risks of incident MACE in a heart disease-free population-based cohort of patients with first-ever ischemic stroke and propensity-matched individuals without stroke. Methods— We included Ontario residents ≥66 years, without known cardiovascular comorbidities, with first-ever ischemic stroke between 2002 and 2012 and propensity-matched individuals without stroke. We investigated the 1-year risk of incident MACE (acute coronary syndrome, myocardial infarction, incident coronary artery disease, coronary revascularization procedures, incident heart failure, or cardiovascular death) separately for females and males. For estimating cause-specific adjusted hazard ratios, we adjusted Cox models for variables with weighted standardized differences >0.10 or those known to influence MACE risk. Results— We included 93 627 subjects without known cardiovascular comorbidities; 21 931 with first-ever ischemic stroke and 71 696 propensity-matched subjects without stroke. Groups were well-balanced on propensity-matching variables. There were 53 476 women (12 421 with and 41 055 without ischemic stroke) and 40 151 men (9510 with and 30 641 without ischemic stroke). First-ever ischemic stroke was associated with increased risk of incident MACE in both sexes. The risk was time-dependent, highest within 30 days (women: adjusted hazard ratio, 25.1 [95% CI, 19.3–32.6]; men: aHR, 23.4 [95% CI, 17.2–31.9]) and decreasing but remaining significant between 31 and 90 days (women: aHR, 4.8 [95% CI, 3.8–6.0]; men: aHR, 4.2 [95% CI, 3.3–5.4]), and 91 to 365 days (aHR, 2.1 [95% CI, 1.8–2.3]; men: aHR, 2.0 [95% CI, 1.7–2.3]). Conclusions— In this large population-based study, ischemic stroke was independently associated with increased risk of incident MACE in both sexes.
First data on microflora of loggerhead sea turtle (Caretta caretta) nests from the coastlines of Sicily

ABSTRACT Caretta caretta is threatened by many dangers in the Mediterranean basin, but most are human-related. The purposes of this research were: (i) to investigate microflora in samples from six loggerhead sea turtle nests located on the Sicilian coast and (ii) to understand microbial diversity associated with nests, with particular attention to bacteria and fungi involved in failed hatchings. During the 2016 and 2018 summers, 456 eggs and seven dead hatchling from six nests were collected. We performed bacteriological and mycological analyses on 88 egg samples and seven dead hatchlings, allowing us to isolate: Fusarium spp. (80.6%), Aeromonas hydrophila (55.6%), Aspergillus spp. (27.2%) and Citrobacter freundii (9%). Two Fusarium species were identified by microscopy and were confirmed by PCR and internal transcribed spacer sequencing. Statistical analyses showed significant differences between nests and the presence/absence of microflora, whereas no significant differences were observed between eggs and nests. This is the first report that catalogues microflora from C. caretta nests/eggs in the Mediterranean Sea and provides key information on potential pathogens that may affect hatching success. Moreover, our results suggest the need for wider investigations over extensive areas to identify other microflora, and to better understand hatching failures and mortality related to microbial contamination in this important turtle species. Summary: We report for the first time the microflora of six loggerhead sea turtle nests on the Sicilian coast, and associated failed hatchings.
Quantitative analysis of liver inflammatory lesions with contrast enhanced ultrasound

Objective To investigate the diagnostic value of contrast enhanced ultrasound(CEUS)in quantitative analysis of liver inflammatory lesions.Methods A total of 22 lesions in 22 patients[16 patients with inflammatory pseudotumor of liver(IPL)and 6 patients with liver abscess]were analyzed retrospectively.Both conventional ultrasound(US)and CEUS were performed in all patients.The diagnosis of liver inflammatory lesions was confirmed by operation or ultrasound guided biopsy.A diagnostic score of 1 to 5 was given to each lesion at US and CEUS.Sonoliver software was used to analyze the dynamical process of both lesion and normal liver tissue with CEUS respectively.The rise time(RT),time to peak(TTP),mean transit time(mTT),maximum intensity(Imax) and the dynamic vascular pattern(DVP) curve was obtained to analyze the differences between liver inflammatory lesions and normal liver tissue,as well as between IPL and liver abscess.The vascular characteristics of the IPL and liver abscess was analyzed.Results Using the score of 1-2 as diagnostic criteria,the accuracy rate of CEUS(63.6%,14/22) was obviously higher than that of US(13.6%,3/22)(χ2=11.6,P0.01). RT of liver inflammatory lesions(25.1±9.1)s was obviously earlier than that of normal liver tissue(32.4±8.8)s(t=-2.6,P0.05). TTP of liver inflammatory lesions(29.0±13.9)s was obviously earlier than that of normal liver tissue(39.3±11.2)s(t=-2.6,P0.05). The mTT and Imax were not significantly different between liver inflammatory lesions and normal liver tissue.The RT,TTP,mTT and Imax between IPL and liver abscess were not significantly different.All the DVP curve of liver inflammatory lesions could be divided into three types:Ⅰ. hyperenhancement without wash-out(18.2%,4/22),Ⅱ. hyperenhancement with wash-out(36.4%,8/22),and Ⅲ. hypoenhancement(45.4%,10/22). Enhancement pattern in arterial phase and shape of necrosis in parenchymal phase were significantly different between IPL and liver abscess(χ2=9.9,8.32;P0.05). In the arterial phase the shape and boundary between IPL and liver abscess were not significantly different.The wash-out rate and boundary between IPL and liver abscess in parenchymal phase were not significantly different.Conclusions CEUS could improve the diagnostic accuracy in liver inflammatory lesions.Quantitative analysis of liver inflammatory lesions with CEUS could provide an objective evaluation on lesion vascularity.
Solid organ donation after death in the United States: Data‐driven messaging to encourage potential donors

US deceased donor solid organ transplantation (dd‐SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the United States. Informing individuals of their own lifetime risk of needing dd‐SOT could reframe the decision‐making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007‐2016), this cross‐sectional study identified (1) deceased organ donors, (2) individuals waitlisted for dd‐SOT (liver, kidney, pancreas, heart, lung, intestine), and (3) dd‐SOT recipients. Using US population projections, life tables, and mortality estimates, we quantified probabilities (Pr) of (1) becoming deceased organ donors, (2) needing dd‐SOT, and (3) receiving dd‐SOT. Lifetime Pr (per 100 000 US population) for males and females of becoming deceased organ donors were 212 and 146, respectively, and of needing dd‐SOT were 1323 and 803, respectively. Lifetime Pr of receiving dd‐SOT was 50% for males, 48% for females. Over a lifetime, males were 6.2 and females 5.5 times more likely to need dd‐SOT than to become deceased organ donors. Organ donation is traditionally contextualized in terms of charity toward others. Our analyses yield a new tool, in the form of quantifying an individual's own likelihood of needing dd‐SOT, which may assist with reframing motivations toward deceased donor organ donation.
Decreased nuclear distribution nudE-like 1 enzyme activity in an animal model with dysfunctional disrupted-in-schizophrenia 1 signaling featuring aberrant neurodevelopment and amphetamine-supersensitivity

Background: Interaction of nuclear-distribution element-like 1 with disrupted-in-schizophrenia 1 protein is crucial for neurite outgrowth/neuronal migration, and this interaction competitively inhibits nuclear-distribution element-like 1 peptidase activity. Nuclear-distribution element-like 1 activity is reduced in antipsychotic-naïve first-episode psychosis and in medicated chronic schizophrenia, with even lower activity in treatment-resistant schizophrenia. Aims: The purpose of this study was to investigate in a rat model overexpressing human non-mutant disrupted-in-schizophrenia 1, with consequent dysfunctional disrupted-in-schizophrenia 1 signaling, the relation of nuclear-distribution element-like 1 activity with neurodevelopment and dopamine-related phenotypes. Methods: We measured cell distribution in striatum and cortex by histology and microtomography, and quantified the basal and amphetamine-stimulated locomotion and nuclear-distribution element-like 1 activity (in blood and brain) of transgenic disrupted-in-schizophrenia 1 rat vs wild-type littermate controls. Results: 3D assessment of neuronal cell body number and spatial organization of mercury-impregnated neurons showed defective neuronal positioning, characteristic of impaired cell migration, in striatum/nucleus accumbens, and prefrontal cortex of transgenic disrupted-in-schizophrenia 1 compared to wild-type brains. Basal nuclear-distribution element-like 1 activity was lower in the blood and also in several brain regions of transgenic disrupted-in-schizophrenia 1 compared to wild-type. Locomotion and nuclear-distribution element-like 1 activity were both significantly increased by amphetamine in transgenic disrupted-in-schizophrenia 1, but not in wild-type. Conclusions: Our findings in the transgenic disrupted-in-schizophrenia 1 rat allow us to state that decreased nuclear-distribution element-like 1 activity reflects both a trait (neurodevelopmental phenotype) and a state (amphetamine-induced dopamine release). We thus define here a role for decreased nuclear-distribution element-like 1 peptidase activity both for the developing brain (the neurodevelopmental phenotype) and for the adult (interaction with dopaminergic responses), and present nuclear-distribution element-like 1 activity in a novel way, as unifying neurodevelopmental with dysfunctional dopamine response phenotypes.
Robotic orthoses for gait rehabilitation: An overview of mechanical design and control strategies

The application of robotic devices in providing physiotherapies to post-stroke patients and people suffering from incomplete spinal cord injuries is rapidly expanding. It is crucial to provide valid rehabilitation for people who are experiencing abnormality in their gait performance; therefore, design and development of newer robotic devices for the purpose of facilitating patients’ recovery is being actively researched. In order to advance the traditional gait treatment among patients, exoskeletons and orthoses were introduced over the last two decades. This article presents a thorough review of existing robotic gait rehabilitation devices. The latest advancements in the mechanical design, types of control and actuation are also covered. The study comprehends discussions on robotic rehabilitation devices developed both for the training on treadmill and over-ground training. The assist-as-needed strategy for the gait training is particularly emphasized while reviewing various control strategies applied to these robotic devices. This study further reviews experimental investigations and clinical assessments of different control strategies and mechanism designs of robotic gait rehabilitation devices using experimental and clinical trials.
Interleukin 6 is increased in preclinical HNSCC models of acquired cetuximab resistance, but is not required for maintenance of resistance

The epidermal growth factor receptor inhibitor cetuximab is the only oncogene-targeted agent that has been FDA approved for the treatment of head and neck squamous cell carcinoma (HNSCC). Currently, there are no biomarkers used in the clinic to predict which HNSCC tumors will respond to cetuximab, and even in tumors that regress with treatment, acquired resistance occurs in the majority of cases. Though a number of mechanisms of acquired resistance to cetuximab have been identified in preclinical studies, no therapies targeting these resistance pathways have yet been effectively translated into the clinic. To address this unmet need, we examined the role of the cytokine interleukin 6 (IL-6) in acquired cetuximab resistance in preclinical models of HNSCC. We found that IL-6 secretion was increased in PE/CA-PJ49 cells that had acquired resistance to cetuximab compared to the parental cells from which they were derived. However, addition of exogenous IL-6 to parental cells did not promote cetuximab resistance, and inhibition of the IL-6 pathway did not restore cetuximab sensitivity in the cetuximab-resistant cells. Further examination of the IL-6 pathway revealed that expression of IL6R, which encodes a component of the IL-6 receptor, was decreased in cetuximab-resistant cells compared to parental cells, and that treatment of the cetuximab-resistant cells with exogenous IL-6 did not induce phosphorylation of signal transducer and activator of transcription 3, suggesting that the IL-6 pathway was functionally impaired in the cetuximab-resistant cells. These findings demonstrate that, even if IL-6 is increased in the context of cetuximab resistance, it is not necessarily required for maintenance of the resistant phenotype, and that targeting the IL-6 pathway may not restore sensitivity to cetuximab in cetuximab-refractory HNSCC.
HDAC inhibition improves cardiopulmonary function in a feline model of diastolic dysfunction

Histone deacetylase inhibition counteracts adverse left ventricular remodeling, improves pulmonary function, and reverses diastolic dysfunction. Counteracting cardiopulmonary dysfunction In patients with heart failure, impaired relaxation of the left ventricle (diastolic dysfunction) results in incomplete filling with blood and increased pressure. Wallner et al. treated a feline model of slow-progressive pressure-overload–induced diastolic dysfunction with the histone deacetylase inhibitor SAHA. SAHA increased myofibril relaxation, improved pulmonary function, reduced left ventricular filling pressures, and reduced left ventricle hypertrophy in cats. The authors determined that SAHA altered acetylation of mitochondrial enzymes, resulting in enhanced mitochondrial respiration. Results suggest that histone deacetylase inhibition could potentially be beneficial for improving cardiopulmonary function. Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on cardiopulmonary structure, function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysfunction common to human HFpEF. Male domestic short-hair felines (n = 31, aged 2 months) underwent a sham procedure (n = 10) or loose aortic banding (n = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, n = 8), a Food and Drug Administration–approved pan-HDAC inhibitor, or vehicle (b + veh, n = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) (P < 0.0001) and left atrium size (P < 0.0001) versus b + veh animals. Left ventricular (LV) end-diastolic pressure and mean pulmonary arterial pressure were significantly reduced in b + SAHA (P < 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and function in patients.
Commentary on evidence in support of a grief‐related condition as a DSM diagnosis

The death of a loved one is one of life's greatest stressors. Most bereaved individuals experience a period of acute grief that diminishes in intensity as they adapt to the changes brought about by their loss. Over the past four decades, a growing body of research has focused on a form of prolonged grief that is painful and impairing. There is a substantial and growing evidence base that supports the validity and significance of a grief‐related disorder, including the clinical value of being able to diagnose it and provide effective targeted treatment. ICD‐11 will include a new diagnosis of prolonged grief disorder (PGD). DSM‐5 called this condition persistent complex bereavement disorder (PCBD) and included it in Section III, signaling agreement that a diagnosis is warranted while further research is needed to determine the optimal criteria. Given the remaining uncertainties, reading this literature can be confusing. There is inconsistency in naming the condition (including complicated grief as well as PGD and PCBD) and lack of uniformity in identifying it, with respect to the optimal threshold and timeframe for distinguishing it from normal grief. As an introductory commentary for this Depression and Anxiety special edition on this form of grief, the authors discuss the history, commonalities, and key areas of variability in identifying this condition. We review the state of diagnostic criteria for DSM‐5 and the current ICD‐11 diagnostic guideline, highlighting the clinical relevance of making this diagnosis.