Miracle-dz/UniFAR-FTUs huggingface dataset:
A Highly Unusual V1 Region of Env in an Elite Controller of HIV Infection

Elite controllers have long provided an avenue for researchers to reveal mechanisms underlying control of HIV-1. While the role of host genetic factors in facilitating elite control is well known, the possibility of infection by attenuated strains of HIV-1 has been much less studied. Here we describe an unusual viral feature found in an elite controller of HIV-1 infection and demonstrate its role in conferring escape from monoclonal antibodies of the V3-glycan class. Our results suggest that extreme variation may be needed by HIV-1 to escape neutralization by some antibody specificities. ABSTRACT HIV elite controllers represent a remarkable minority of patients who maintain normal CD4+ T-cell counts and low or undetectable viral loads for decades in the absence of antiretroviral therapy. To examine the possible contribution of virus attenuation to elite control, we obtained a primary HIV-1 isolate from an elite controller who had been infected for 19 years, the last 10 of which were in the absence of antiretroviral therapy. Full-length sequencing of this isolate revealed a highly unusual V1 domain in Envelope (Env). The V1 domain in this HIV-1 strain was 49 amino acids, placing it in the top 1% of lengths among the 6,112 Env sequences in the Los Alamos National Laboratory online database. Furthermore, it included two additional N-glycosylation sites and a pair of cysteines suggestive of an extra disulfide loop. Virus with this Env retained good infectivity and replicative capacity; however, analysis of recombinant viruses suggested that other sequences in Env were adapted to accommodate the unusual V1 domain. While the long V1 domain did not confer resistance to neutralization by monoclonal antibodies of the V1/V2-glycan-dependent class, it did confer resistance to neutralization by monoclonal antibodies of the V3-glycan-dependent class. Our findings support results in the literature that suggest a role for long V1 regions in shielding HIV-1 from recognition by V3-directed broadly neutralizing antibodies. In the case of the elite controller described here, it seems likely that selective pressures from the humoral immune system were responsible for driving the highly unusual polymorphisms present in this HIV-1 Envelope. IMPORTANCE Elite controllers have long provided an avenue for researchers to reveal mechanisms underlying control of HIV-1. While the role of host genetic factors in facilitating elite control is well known, the possibility of infection by attenuated strains of HIV-1 has been much less studied. Here we describe an unusual viral feature found in an elite controller of HIV-1 infection and demonstrate its role in conferring escape from monoclonal antibodies of the V3-glycan class. Our results suggest that extreme variation may be needed by HIV-1 to escape neutralization by some antibody specificities.
A Test of Competing Models of the Relationships Among Perceptions of Organizational Politics, Perceived Organizational Support, and Individual Outcomes

The authors aimed to distinguish between perceptions of organizational politics (POPs) and perceived organizational support (POS). Previous research has shown that these two constructs are related, and whereas some researchers have suggested that POS mediates the relationships between POPs and outcomes (e.g., M. C. Andrews & K. M. Kacmar, 2001; R. Cropanzano, J. C. Howes, A. A. Grandey, & P. Toth, 1997), others have claimed that POPs mediate the relationships between POS and outcomes (e.g., G. R. Ferris, G. S. Russ, & P. M. Fandt, 1989). The authors investigated these competing models in an organizational sample of 418 employees from a water-management-district office. Results showed that POPs and POS were related to each other and to 5 outcomes: (a) job satisfaction, (b) pay satisfaction, (c) job strains, (d) role conflicts, and (e) turnover intentions. Results also indicated that POS fully mediated 3 of the 5 relationships between POPs and outcomes and partially mediated the other 2.
Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
Application of Machine Learning Methods to Predict Non-Alcoholic Steatohepatitis (NASH) in Non-Alcoholic Fatty Liver (NAFL) Patients

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. NAFLD patients have excessive liver fat (steatosis), without other liver diseases and without excessive alcohol consumption. NAFLD consists of a spectrum of conditions: benign steatosis or non-alcoholic fatty liver (NAFL), steatosis accompanied by inflammation and fibrosis or nonalcoholic steatohepatitis (NASH), and cirrhosis. Given a lack of clinical biomarkers and its asymptomatic nature, NASH is under-diagnosed. We use electronic health records from the Optum Analytics to (1) identify patients diagnosed with benign steatosis and NASH, and (2) train machine learning classifiers for NASH and healthy (non-NASH) populations to (3) predict NASH disease status on patients diagnosed with NAFL. Summarized temporal lab data for alanine aminotransferase, aspartate aminotransferase, and platelet counts, with basic demographic information and type 2 diabetes status were included in the models.
Functional deficiency in endogenous interleukin‐1 receptor antagonist in patients with febrile infection‐related epilepsy syndrome

We recently reported successful treatment of a child with febrile infection‐related epilepsy syndrome (FIRES), a subtype of new onset refractory status epilepticus, with the recombinant interleukin‐1 (IL1) receptor antagonist (IL1RA) anakinra. On this basis, we tested whether endogenous IL1RA production or function is deficient in FIRES patients.
The sensitivity and specificity of the balance evaluation systems test-BESTest in determining risk of fall in stroke patients.

BACKGROUND Balance disorders cause disability in stroke and increase risk of falls. The Balance Evaluation Systems Test (BESTest), examines balance, determines parameters causing balance disorders, provides information on risk factors for falls. OBJECTIVE To investigate the sensitivity and specificity of the BESTest in determining the risk of falls in stroke patients. METHODS Fifty patients with chronic stroke were included in the study. Balance was assessed using BESTest, Berg Balance Scale (BBS), Activity Specific Balance Confidence scale (ABC) and Biodex-BioSway Balance System. To examine the content validity of BESTest, the relationship between BESTest and other balance assessment methods was examined. The internal consistency reliability of BESTest was evaluated by Cronbach's α coefficient. Analysis of receiver operating characteristics (ROC) was performed to determine cut-off point, sensitivity and specificity. RESULTS BESTest, BBS, ABC and Biodex-BioSway Balance System results of faller stroke patients were worse than that of non-faller (p <0.05). Internal consistency of BESTest was found to be Cronbach's α = 0.960. The BESTest value of area under curve (AUC) was 0.844, with a cut-off point of 69.44%, a sensitivity of 75% and a specificity of 84.6% (p < 0.01). CONCLUSION BESTest is reliable and valid with high sensitivity and specificity in determining the risk of fall in stroke patients.
Effects of breed and different lipid dietary supplements on beef quality.

Focus of this study was to evaluate the most suitable breed/crossbred and the appropriate nutritional strategies to increase marbling in beef muscle and to improve its healthy properties, in particular the n-3 fatty acids content. One hundred and seventy-six heifers of three crossbreed commonly reared by Emilia-Romagna farmers: 48 Bleu Belge × Freisian (ITA), 48 Charolais × Aubrac (FRA), and 80 Angus (ANG) were used. Animals of each breed were randomly subdivided in two experimental groups that received two diets, differing for the dietary lipid source. Control group (C) received a basal diet containing protected vegetable fats, whereas treated one (T) received the same basal diet supplemented with 0.9 kg/head/day of extruded flaxseed. After slaughtering, a sample of Longissimus thoracis was collected from each animal for meat quality analysis. Our results demonstrated that, in a shorter fattening period, ANG animals obtained the best dry matter intake, average daily gain and the best fattening scores. ITA and ANG meat presented the highest marbling scores. ANG breed had the highest amount of C18:1, the highest unsaturated/saturated fatty acids ratio and the lowest n-6/n-3 ratio. The T animals, independently from breed, showed the highest amount of α-linolenic acid (ALA). In addition, ANG-T meat presented the highest ALA content.
Rapamycin Corrects T Regulatory Cell Depletion and Improves Embryo Implantation and Live Birth Rates in a Murine Model

There are few treatments for patients with recurrent pregnancy loss (RPL) or recurrent implantation failure (RIF). Women with RPL and unexplained infertility have lower T regulatory cell (Treg) expression when compared to fertile controls. A murine model has been developed with depletion of regulatory T cells (DEREG) after administration of diphtheria toxin (DT), resulting in smaller litter sizes, secondary to embryo implantation failure. Numerous murine studies have shown that adoptive transfer of CD4+CD25+FoxP3+ Tregs from donors improves litter sizes in DEREG mice with depleted Tregs. Our hypothesis is that DEREG mice treated with a single dose of DT will deplete Tregs and subsequently decrease litter sizes and that treatment with rapamycin (sirolimus; Pfizer) during the time of embryo implantation will increase Tregs and restore litter sizes nearly back to normal levels. Syngeneic mating of DEREG mice after depletion of Tregs resulted in smaller litter sizes and this defect was reversed when these DEREG mice were treated with rapamycin at the time of embryo implantation. The importance of Tregs at the time of embryo implantation has been well established and immunotherapy treatments, such as rapamycin (mammalian target of rapamycin inhibitor), may prove to be an effective treatment for patients with RPL, RIF, or unexplained infertility with low Treg.
Noninvasive ventilation and weaning in patients with chronic hypercapnic respiratory failure: a randomized multicenter trial.

RATIONALE The use of noninvasive ventilation (NIV) as an early weaning/extubation technique from mechanical ventilation remains controversial. OBJECTIVES To investigate NIV effectiveness as an early weaning/extubation technique in difficult-to-wean patients with chronic hypercapnic respiratory failure (CHRF). METHODS In 13 intensive care units, 208 patients with CHRF intubated for acute respiratory failure (ARF) who failed a first spontaneous breathing trial were randomly assigned to three groups: conventional invasive weaning group (n = 69), extubation followed by standard oxygen therapy (n = 70), or NIV (n = 69). NIV was permitted as rescue therapy for both non-NIV groups if postextubation ARF occurred. Primary endpoint was reintubation within 7 days after extubation. Secondary endpoints were: occurrence of postextubation ARF or death within 7 days after extubation, use of rescue postextubation NIV, weaning time, and patient outcomes. MEASUREMENTS AND MAIN RESULTS Reintubation rates were 30, 37, and 32% for invasive weaning, oxygen-therapy, and NIV groups, respectively (P = 0.654). Weaning failure rates, including postextubation ARF, were 54, 71, and 33%, respectively (P < 0.001). Rescue NIV success rates for invasive and oxygen-therapy groups were 45 and 58%, respectively (P = 0.386). By design, intubation duration was 1.5 days longer for the invasive group than in the two others. Apart from a longer weaning time in NIV than in invasive group (2.5 vs. 1.5 d; P = 0.033), no significant outcome difference was observed between groups. CONCLUSIONS No difference was found in the reintubation rate between the three weaning strategies. NIV decreases the intubation duration and may improve the weaning results in difficult-to-wean patients with CHRF by reducing the risk of postextubation ARF. The benefit of rescue NIV in these patients deserves confirmation.
Indications for Pediatric External Ventricular Drain Placement and Risk Factors for Conversion to a Ventriculoperitoneal Shunt

Background/Aims: The external ventricular drain (EVD) is commonly used for the treatment of hydrocephalus and intracranial pressure (ICP) monitoring. In this study, we retrospectively reviewed indications for EVD placement over the last 20 years in pediatric patients at our institution. Additionally, we evaluated the rate that an EVD needed to be converted to a ventriculoperitoneal shunt (VPS) and ascertained how hydrocephalus etiology impacted long-term drainage requirements. Methods: Patients that received an EVD between 1990 and 2010 at our institution were identified using billing codes. Demographics, etiology of hydrocephalus, length of stay (LOS) and EVD duration were recorded. Only patients receiving their first EVD were included; those with any prior ventricular catheter (including prior shunts) were excluded from this study. Results: A total of 180 patients underwent first-time placement of an EVD over the 20-year period. Of these, 78.9% were placed on the right side and 81.7% were performed through a frontal burr hole site. The average age of all patients at their initial procedure was 9.3 years (median 9.8; range 0-18), hospital LOS was 22.5 days (median 16; range 1-174) and EVD duration was 7.8 days (median 7; range 1-37). Trauma (43.3%) and neoplasms (32.2%) were the most common indications. Approximately, one quarter of the patients were unable to become EVD independent and, therefore, required a VPS. Only patients receiving an EVD for traumatic brain injury were significantly less likely to be converted to a shunt than other causes of hydrocephalus (relative risk, RR = 0.18, 95% confidence interval, CI = 0.07-0.46). Conversely, patients with neoplasms (RR = 3.56, 95% CI = 1.74-7.31), obstructive hydrocephalus (RR = 5.48, 95% CI = 1.37-22.0) and intraventricular hemorrhage (RR = 9.86, 95% CI = 1.05-92.3) were more likely to need a shunt. Conclusion: Traumatic brain injuries and neoplasms represent the most common indications for EVD placement in the pediatric population. While patients with neoplasm were much more likely to need conversion to a VPS for long-term cerebrospinal fluid diversion, the majority of EVDs in patients with head injuries were successfully weaned.
A Standardized Evaluation Method for FOXP3+ Tregs and CD8+ T-cells in Breast Carcinoma: Association With Breast Carcinoma Subtypes, Stage and Prognosis

Background/Aim: The role of FOXP3+ Tregs and CD8+ T-cells in different stages and subtypes of breast carcinoma (BC) is yet to be fully defined, mainly because of methodological variations between studies. The aim of this study was to assess FOXP3+ and CD8+ intratumoral stromal TILs (sTILs) by a standardized method, in order to discern differences between the histological subtypes and BC stage and evaluate the applicability of the method. Patients and Methods: FOXP3+ and CD8+ sTILs were studied immunohistochemically in 207 BCs and counted on digital images, amounting to a standard stromal area of a 10×10 grid on ×40 magnification. The results were correlated with clinicopathological features and outcomes. Results: Tregs and CD8+ TILs were more abundant in HER2+ BCs (p=0.02, p=0.007, respectively), estrogen receptor (ER)-BCs (p<0.001, for both cell types), and triple-negative BCs (TNBCs) (p=0.01, p=0.006, respectively). Tregs and CD8+ TILs were associated with high grade (p<0.001 and p=0.002, respectively) and high Ki67 index (p<0.001, for both cell types). Lower CD8/FOXP3 ratio was associated with node metastases (p=0.007). Node metastases and advanced stage paralleled with decreased CD8+ sTILs (p=0.023, p=0.019, respectively). In the entire group and in ER− BCs, CD8+ TILs were associated with favorable distant metastasis-free survival (p=0.021, p<0.001, respectively), disease-free survival (p=0.022, p<0.001, respectively) and breast cancer specific survival (BCSS) (p=0.022, p=0.005). In ER-BCs, Tregs were associated with favorable BCSS (p=0.02). Conclusion: Tregs and CD8+ TILs are higher in early-stage TNBCs and HER2+ BCs and diminish with progression to advanced stages. The findings provide support for immunotherapeutic manipulation of TILs, particularly in early stages of these BC subtypes. The evaluation methodology can be easily implemented for standardization of immunohistochemically-detected TILs.
A Subpopulation of Amygdala Neurons Mediates the Affective Component of Itch

Itch consists of both sensory and affective components. For chronic itch patients, the affective component of itch affects both quality of life (leading to psychological comorbidities) and disease prognosis (by promoting scratching of itchy skin). We found that acute itch stimuli, such as histamine, induced anxiety-like behavior and increased activity (c-Fos expression) in the amygdala in adult male C57BL/6 mice. Itch stimuli also increased activity in projection areas to the amygdala, suggesting that these regions form a circuit for affective itch processing. Electrophysiological characterization of histamine-responsive amygdala neurons showed that this population was active on a behaviorally relevant timescale and partially overlapped with pain signaling. Selective optogenetic activation of histamine-responsive amygdala neurons in adult male and female Fos:CreERT2;R26Ai14 mice using the Targeted Recombination in Active Populations system enhanced both scratching and anxiety-like behavior. These results highlight the importance of itch-responsive amygdala neurons in modulating itch-related affect and behavior. SIGNIFICANCE STATEMENT The sensation of itch includes an affective component that leads to stress and anxiety in chronic itch patients. We investigated the neuronal basis of affective itch in mice, with a focus on the amygdala, the key brain region for the generation of anxiety. A subpopulation of amygdala neurons responded to itch stimuli such as histamine. Optogenetic activation of histamine-responsive amygdala neurons affected both scratching and anxiety-like behavior. Therefore, this population appears to be important for mediating the affective component of itch.
Patch-scale culls of an overabundant bird defeated by immediate recolonization.

Overabundant native animals cause a variety of human-wildlife conflicts that can require management to reduce their social, environmental, or economic impacts. Culling is an intuitively attractive management response to overabundance, but poor monitoring of results and costs means that evidence for successful outcomes is often lacking. Furthermore, many culls worldwide have been ineffective or counterproductive due to ecological release mechanisms or compensatory responses by the overabundant species. We completed a controlled, replicated, costed, and rigorously monitored experimental cull of the endemic Australian honeyeater, the Noisy Miner (Manorina melanocephala). Aggressive exclusion of birds from remnant woodland patches by overabundant Noisy Miners is listed as a Key Threatening Process under Australian conservation legislation due to its impacts on threatened birds. The problem is particularly prevalent in the highly modified agricultural landscapes of eastern Australia. The species impacts avian assemblages at low densities (0.6-0.8 birds/ha) and at a subcontinental scale (>1 million km2 ). Some ecologists recommend culling as the only management response capable of timely reversal of declines of threatened small woodland birds. We monitored Noisy Miner abundance before and for 12 months after a culling program and found that immediate recolonization from the surrounding landscape negated the impact of the cull. We hypothesize that this is due to a vacuum effect; whereby, birds resident in more marginal habitat around treatment patches move into the vacant territory post-cull. Modeled mean abundance of Noisy Miners declined by 22% in treatment sites compared to an increase of 4% in control sites in the post-cull period. Abundance in all sites, however, remained three to five times higher than published ecological impact thresholds. Return on investment analysis indicated no relationship between culling effort and reduction in Noisy Miner abundance. We conclude that culling at a patch scale is not an efficient method of reducing Noisy Miner abundance to levels unlikely to impact threatened woodland birds in the highly modified study landscape, despite estimated costs 18 times lower than another potential management response of revegetation. Our study highlights the importance of building empirical evidence before intuitively attractive but not necessarily ecologically effective management responses are applied more widely.
Genital Self-Image: Associations with Other Domains of Body Image and Sexual Response

Abstract Genital self-image is an emerging aspect of body image relevant to sexual functioning and sexual satisfaction. The aims of the present study were to (1) examine the association between body image and genital self-image with a broad range of sexuality-related outcomes; (2) explore whether genital self-image is a more salient influence on sexual satisfaction and functioning than body image and (3) determine whether this would hold true for both men and women. The analytic sample (6,228 cis-gendered, heterosexual men and women between the ages of 18 and 40) was recruited from reddit.com online communities. Participants completed a survey that assessed genital self-image, body image, sexual satisfaction, and sexual functioning. Among women and men, positive genital self-image was associated with positive feelings about one’s body overall and reduced body-related concerns specific to sexual encounters (e.g., sexual performance). In female respondents, as genital self-image increased, so did sexual satisfaction. Although genital self-image did not significantly predict sexual satisfaction among men, exploratory analysis indicated a mediating relationship with body image concerns. Findings from the current study may inform interventions to facilitate the development of a healthy sexual self-concept as well as a more positive outlook on genital appearance among men and women.