Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinicopathologic Profile of Breast Cancer in Germline ATM and CHEK2 Mutation Carriers

The most common breast cancer (BC) susceptibility genes beyond BRCA1/2 are ATM and CHEK2. For the purpose of exploring the clinicopathologic characteristics of BC developed by ATM or CHEK2 mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen ATM and 17 CHEK2 mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in ATM (26.3%) and CHEK2 mutation carriers (41.2%). While 64.3% of CHEK2 tumors were luminal A-like, 56.2% of ATM tumors were luminal B-like/HER2-negative. Moreover, 21.4% of CHEK2-related invasive tumors showed a lobular histotype. About a quarter of all ATM-related BCs and a third of CHEK2 BCs were in situ carcinomas and more than half of ATM and CHEK2-related BCs were diagnosed at stage I-II. Finally, 63.2% of ATM mutation carriers and 64.7% of CHEK2 mutation carriers presented a positive BC family history. The biological and clinical characteristics of ATM and CHEK2-related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with ATM and CHEK2 mutation carriers at the first diagnosis of BC.
Direct Oral Anticoagulants versus Vitamin K Antagonists in Patients Aged 80 Years and Older

The effectiveness of direct oral anticoagulants (DOAC) is non-inferior to vitamin K antagonists (VKA) to treat atrial fibrillation and venous thromboembolism (VTE). In this cross-sectional study, we compared older persons taking DOACs to those taking VKAs. We included ambulatory individuals ≥80 years, affiliated to Mutualité Sociale Agricole of Burgundy, who were refunded for a medical prescription in September 2017. The demographic conditions, registered chronic diseases (RCD), and number and types of prescribed drugs were compared in the DOAC group and VKA group. Of the 3190 included individuals, 1279 (40%) were prescribed DOACs and 1911 (60%) VKAs. Individuals taking VKAs were older than those taking DOACs (87.11 vs. 86.35 years). In the DOAC group, there were more women (51.92% vs. 48.25%) (p = 0.043), less RCD (89.60% vs. 92.73%) (p = 0.002), less VTE (1.80% vs. 6.59%), less severe heart failure (58.09% vs. 67.87%), less severe hypertension (18.22% vs. 23.60%), less severe kidney diseases (1.49% vs. 3.82%), and fewer drugs per prescription (6.15 vs. 6.66) (p < 0.01 for all). The DOAC group were also less likely to be taking angiotensin receptor blockers (10.79% vs. 13.97%), furosemide (40.81% vs. 49.66%) or digoxin (10.32% vs. 13.66%) than the VKA group (p = 0.009, p < 0.001, and p = 0.005). DOACs were less prescribed than VKAs. Individuals taking VKAs were older and had more severe comorbidities and more drugs per prescription than those taking DOACs.
Effects of Supplementing Rumen-Protected Methionine and Lysine on Milk Performance and Oxidative Status of Dairy Ewes

There is limited information on the impact of dietary supplementation with separate rumen-protected (RP) amino acids (AA), or with their combination, on ewes’ oxidative status. Sixty ewes were divided into five groups; C: basal diet (control); M: basal diet + 6 g/ewe RP methionine; L: basal diet + 5 g/ewe RP lysine; LML: basal diet + 6 g methionine and 5 g lysine/ewe; and HML: basal diet + 12 g methionine + 5 g lysine/ewe. Milk’s fat content increased in RP-AA fed ewes, while that of protein in M and L only. In blood plasma, the malondialdehyde (MDA) content was reduced in the M, LML, and HML compared to C-fed ewes. An increase in glutathione transferase activity in the blood plasma of the M and LML compared to the C and HML-fed ewes were found. In milk, lower values of the ferric reducing ability of plasma (FRAP) in the LML and HML-fed ewes and of 2,2′-Azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS) in LML only, were found. Lysine increased milk’s FRAP values and MDA content. Both L and HML diets increased milk’s protein carbonyls content. Methionine improves the organism’s oxidative status, without adversely affecting milk’s oxidative stability. Lysine dietary inclusion affects negatively the oxidative stability of milk.
ATF3-Expressing Large-Diameter Sensory Afferents at Acute Stage as Bio-Signatures of Persistent Pain Associated with Lumbar Radiculopathy

The mechanism of pain chronicity is largely unknown in lumbar radiculopathy (LR). The anatomical location of nerve injury is one of the important factors associated with pain chronicity of LR. Accumulating evidence has shown constriction distal to the dorsal root ganglion (DRG) caused more severe radiculopathy than constriction proximal to the DRG; thereby, the mechanism of pain chronicity in LR could be revealed by comparing the differences in pathological changes of DRGs between nerve constriction distal and proximal to the DRG. Here, we used 2 rat models of LR with nerve constriction distal or proximal to the DRG to probe how the different nerve injury sites could differentially affect pain chronicity and the pathological changes of DRG neuron subpopulations. As expected, rats with nerve constriction distal to the DRG showed more persistent pain behaviors than those with nerve constriction proximal to the DRG in 50% paw withdraw threshold, weight-bearing test, and acetone test. One day after the operation, distal and proximal nerve constriction showed differential pathological changes of DRG. The ratios of activating transcription factor3 (ATF3)-positive DRG neurons were significantly higher in rats with nerve constriction distal to DRG than those with nerve constriction proximal to DRG. In subpopulation analysis, the ratios of ATF3-immunoreactivity (IR) in neurofilament heavy chain (NFH)-positive DRG neurons significantly increased in distal nerve constriction compared to proximal nerve constriction; although, both distal and proximal nerve constriction presented increased ratios of ATF3-IR in calcitonin gene-related peptide (CGRP)-positive DRG neurons. Moreover, the nerve constriction proximal to DRG caused more hypoxia than did that distal to DRG. Together, ATF3 expression in NHF-positive DRG neurons at the acute stage is a potential bio-signature of persistent pain in rat models of LR.
Measuring Gait Velocity and Stride Length with an Ultrawide Bandwidth Local Positioning System and an Inertial Measurement Unit

One possible modality to profile gait speed and stride length includes using wearable technologies. Wearable technology using global positioning system (GPS) receivers may not be a feasible means to measure gait speed. An alternative may include a local positioning system (LPS). Considering that LPS wearables are not good at determining gait events such as heel strikes, applying sensor fusion with an inertial measurement unit (IMU) may be beneficial. Speed and stride length determined from an ultrawide bandwidth LPS equipped with an IMU were compared to video motion capture (i.e., the “gold standard”) as the criterion standard. Ninety participants performed trials at three self-selected walk, run and sprint speeds. After processing location, speed and acceleration data from the measurement systems, speed between the last five meters and stride length in the last stride of the trial were analyzed. Small biases and strong positive intraclass correlations (0.9–1.0) between the LPS and “the gold standard” were found. The significance of the study is that the LPS can be a valid method to determine speed and stride length. Variability of speed and stride length can be reduced when exploring data processing methods that can better extract speed and stride length measurements.
HIV-1 Entry and Membrane Fusion Inhibitors

HIV-1 (human immunodeficiency virus type 1) infection begins with the attachment of the virion to a host cell by its envelope glycoprotein (Env), which subsequently induces fusion of viral and cell membranes to allow viral entry. Upon binding to primary receptor CD4 and coreceptor (e.g., chemokine receptor CCR5 or CXCR4), Env undergoes large conformational changes and unleashes its fusogenic potential to drive the membrane fusion. The structural biology of HIV-1 Env and its complexes with the cellular receptors not only has advanced our knowledge of the molecular mechanism of how HIV-1 enters the host cells but also provided a structural basis for the rational design of fusion inhibitors as potential antiviral therapeutics. In this review, we summarize our latest understanding of the HIV-1 membrane fusion process and discuss related therapeutic strategies to block viral entry.
New Sequence Type ST3449 in Multidrug-Resistant Pseudomonas aeruginosa Isolates from a Cystic Fibrosis Patient

Pseudomonas aeruginosa is one of the most critical bacterial pathogens associated with chronic infections in cystic fibrosis patients. Here we show the phenotypic and genotypic characterization of five consecutive multidrug-resistant isolates of P. aeruginosa collected during a month from a CF patient with end-stage lung disease and fatal outcome. The isolates exhibited distinct colony morphologies and pigmentation and differences in their capacity to produce biofilm and virulence potential evaluated in larvae of Galleria mellonella. Whole genome-sequencing showed that isolates belonged to a novel sequence type ST3449 and serotype O6. Analysis of their resistome demonstrated the presence of genes blaOXA-396, blaPAO, aph(3’)-IIb, catB, crpP and fosA and new mutations in chromosomal genes conferring resistance to different antipseudomonal antibiotics. Genes exoS, exoT, exoY, toxA, lasI, rhlI and tse1 were among the 220 virulence genes detected. The different phenotypic and genotypic features found reveal the adaptation of clone ST3449 to the CF lung environment by a number of mutations affecting genes related with biofilm formation, quorum sensing and antimicrobial resistance. Most of these mutations are commonly found in CF isolates, which may give us important clues for future development of new drug targets to combat P. aeruginosa chronic infections.
COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program — Kentucky, March 2021

Although COVID-19 mRNA vaccines demonstrated high efficacy in clinical trials (1), they were not 100% efficacious. Thus, some infections postvaccination are expected. Limited data are available on effectiveness in skilled nursing facilities (SNFs) and against emerging variants. The Kentucky Department for Public Health (KDPH) and a local health department investigated a COVID-19 outbreak in a SNF that occurred after all residents and health care personnel (HCP) had been offered vaccination. Among 83 residents and 116 HCP, 75 (90.4%) and 61 (52.6%), respectively, received 2 vaccine doses. Twenty-six residents and 20 HCP received positive test results for SARS-CoV-2, the virus that causes COVID-19, including 18 residents and four HCP who had received their second vaccine dose >14 days before the outbreak began. An R.1 lineage variant was detected with whole genome sequencing (WGS). Although the R.1 variant has multiple spike protein mutations, vaccinated residents and HCP were 87% less likely to have symptomatic COVID-19 compared with those who were unvaccinated. Vaccination of SNF populations, including HCP, is critical to reduce the risk for SARS-CoV-2 introduction, transmission, and severe outcomes in SNFs. An ongoing focus on infection prevention and control practices is also essential.
The Relationship between Intelligence and Divergent Thinking—A Meta-Analytic Update

This paper provides a meta-analytic update on the relationship between intelligence and divergent thinking (DT), as research on this topic has increased, and methods have diversified since Kim’s meta-analysis in 2005. A three-level meta-analysis was used to analyze 849 correlation coefficients from 112 studies with an overall N = 34,610. The overall effect showed a significant positive correlation of r = . 25. This increase of the correlation as compared to Kim’s prior meta-analytic findings could be attributed to the correction of attenuation because a difference between effect sizes prior-Kim vs. post-Kim was non-significant. Different moderators such as scoring methods, instructional settings, intelligence facets, and task modality were tested together with theoretically relevant interactions between some of these factors. These moderation analyses showed that the intelligence–DT relationship can be higher (up to r = .31–.37) when employing test-like assessments coupled with be-creative instructions, and considering DT originality scores. The facet of intelligence (g vs. gf vs. gc) did not affect the correlation between intelligence and DT. Furthermore, we found two significant sample characteristics: (a) average sample age was positively associated with the intelligence–DT correlation, and (b) the intelligence–DT correlation decreased for samples with increasing percentages of females in the samples. Finally, inter-moderator correlations were checked to take potential confounding into account, and also publication bias was assessed. This meta-analysis provides a comprehensive picture of current research and possible research gaps. Theoretical implications, as well as recommendations for future research, are discussed.
Parent and Peer Emotion Responsivity Styles: An Extension of Gottman’s Emotion Socialization Parenting Typologies

This theoretical paper introduces six emotion socialization typologies that can be used for designating emotion responsivity styles of parents and peers of children in middle childhood, referred to as Parent and Peer Emotion Responsivity Styles (PPERS). This typology draws on theoretical foundations of meta-emotion and emotion socialization. These typologies are compliment with and extend Gottman’s emotion-based parenting styles, as they are organized generally by whether the response is more positive or more negative and whether the response is more emotionally constructive or destructive, but extend the four styles to include whether the parent or peer targets the emotion directly when responding to a child’s emotions, or whether they target the emotion-related behavior. On the positive end, there is the Emotion Constructive style, which targets the child’s emotions directly. The other two positive styles include Emotion Responsive and Emotion Acceptive, which target the child’s emotional behaviors with higher or lower levels of activity. On the negative side, there is the Emotion Destructive style which is employed to target the emotion itself, while the Emotion Punitive and Emotion Dismissive styles target the child’s emotion-related behavior with varying levels of activity. Implications for the development and study of these theoretical typologies are discussed.
Higher circulating intermediate monocytes are associated with cognitive function in women with HIV

BACKGROUND Identifying a quantitative biomarker of neuropsychiatric dysfunction in people with HIV (PWH) remains a significant challenge in the neuroHIV field. The strongest evidence to date implicates the role of monocytes in central nervous system (CNS) dysfunction in HIV, yet no study has examined monocyte subsets in blood as a correlate and/or predictor of neuropsychiatric function in virally suppressed PWH. METHODS In 2 independent cohorts of virologically suppressed women with HIV (vsWWH; n = 25 and n = 18), whole blood samples were obtained either in conjunction with neuropsychiatric assessments (neuropsychological [NP] test battery, self-report depression and stress-related symptom questionnaires) or 1 year prior to assessments. Immune cell subsets were assessed by flow cytometry. RESULTS A higher proportion of intermediate monocytes (CD14+CD16+) was associated with lower global NP function when assessing monocytes concurrently and approximately 1 year before (predictive) NP testing. The same pattern was seen for executive function (mental flexibility) and processing speed. Conversely, there were no associations with monocyte subsets and depression or stress-related symptoms. Additionally, we found that a higher proportion of classical monocytes was associated with better cognition. CONCLUSION Although it is widely accepted that lentiviral infection of the CNS targets cells of monocyte-macrophage-microglial lineage and is associated with an increase in intermediate monocytes in the blood and monocyte migration into the brain, the percentage of intermediate monocytes in blood of vsWWH has not been associated with neuropsychiatric outcomes. Our findings provide evidence for a new, easily measured, blood-based cognitive biomarker in vsWWH. FUNDING R01-MH113512, R01-MH113512-S, P30-AI094189, R01-MH112391, R01-AI127142, R00-DA044838, U01-AI35004, and P30-MH075673
Glyphosate Herbicide Induces Changes in the Growth Pattern and Somatic Indices of Crossbred Red Tilapia (O. niloticus × O. mossambicus)

Simple Summary In this study, a chronic, seven-week study of the effect of technical grade glyphosate on the toxicity parameters of crossbred red tilapia (O. niloticus × O. mossambicus) was carried out. The results show that the bodyweight index was the most sensitive toxicity parameter wherein a reduction in body weight was observed at 25 mg/L of glyphosate. Negative correlations between the glyphosate concentration and toxicity parameters such as specific growth rate (SGR), hepato-somatic index (HIS), and gonado-somatic index (GSI) were observed. The fish condition factor and feed conversion ratio were found to be unaffected at the highest glyphosate concentration tested (150 mg/L). Abstract The development of glyphosate-resistant genetically modified organisms (GMO) has increased the use of herbicide glyphosate by several magnitudes in recent years. It is now the most commonly used pesticide globally that affects aquatic habitats, especially fish. This study aims to add new knowledge on the effect of technical grade glyphosate on several toxicity parameters and to identify the most effective parameter in predicting technical grade glyphosate chronic toxicity (seven weeks) to fish, especially Malaysia’s heavily farmed red tilapia. The results show that a relatively high concentration of technical grade glyphosate is needed to induce significant changes in all tested parameters. However, the results also indicate that the bodyweight index is the most sensitive toxicity parameter in that a reduction in body weight was observed at 25 mg/L of glyphosate. Negative correlations between the glyphosate concentration and toxicity parameters such as specific growth rate (SGR), hepato-somatic index (HIS), and gonado-somatic index (GSI) were observed. The fish condition factor and feed conversion ratio were found not to be affected at the highest glyphosate concentration tested (150 mg/L). To conclude, crossbred red tilapia (O. niloticus × O. mossambicus) is one potential species for evaluating the toxic effects of technical grade glyphosate on fish.
Application of the Ridden Horse Pain Ethogram to Elite Dressage Horses Competing in World Cup Grand Prix Competitions

Simple Summary A Ridden Horse Pain Ethogram (RHpE) was developed comprising 24 behaviours; a score of ≥8/24 is likely to reflect the presence of musculoskeletal pain. The aim of the study was to apply the RHpE to elite dressage horses, competing at World Cup Grand Prix qualifying competitions or finals. It was hypothesised that this should be a group of horses with a low incidence of musculoskeletal pain; thus, RHpE scores would be consistently <8. Additional aims were to compare RHpE scores with judges’ scores and to compare these and other observations concerning gait with the guidelines for judging Fédération Equestre Internationale (FEI) dressage. The RHpE was applied by a trained assessor to video recordings of 147 competitors at nine venues. Freehand notes described additional observations. The median RHpE score for all competitors was 3/24 (range 0, 7). There was a moderate negative correlation between the RHpE score and the judges’ score. There was a high frequency of occurrence of head behind vertical ≥10° ≥10 s, mouth open with separation of the teeth ≥10 s and repeated tail swishing, behaviours that should be penalised according to FEI rules. It was nonetheless concluded that most horses appeared to work comfortably for the majority of the test. Abstract There is considerable debate about the social license to compete with horses and controversy about training methods for dressage horses. The objectives were to: 1. apply the Ridden Horse Pain Ethogram (RHpE) to dressage horses competing at elite Grand Prix level; 2. compare RHpE and judges’ scores; and 3. document deviations in gaits from Fédération Equestre Internationale (FEI) guidelines. Video recordings of 147 competitors from nine World Cup competitions were assessed. Spearman’s rank correlation coefficient tested the correlation between RHpE and judges’ scores. The median RHpE score was 3 (IQR 1, 4; range 0, 7). There was a moderate negative correlation (Spearman rho −0.40, p < 0.001) between the RHpE scores and the judges’ scores. Mouth open with separation of the teeth for ≥10 s (68%), head behind vertical ≥10° ≥10 s (67%), an intense stare for ≥5 s (30%) and repeated tail swishing (29%) were the most frequent RHpE behaviours. Deviations from FEI guidelines were most frequent in passage, piaffe, canter flying-changes, canter pirouettes and “halt-immobility-rein back five steps-collected trot”. In conclusion, most horses appeared to work comfortably for the majority of the test. Further investigation of the influence of a double bridle compared with a snaffle bridle on head position and mouth opening is merited.
Prognostic Impact of PD-L1 Expression in pN1 NSCLC: A Retrospective Single-Center Analysis

Simple Summary The analysis of prognostic biomarkers (e.g., PD-L1) helps to define treatment for lung cancer patients. To date, these markers have only been examined in metastatic or inoperable situations. We analyzed the PD-L1 expression-levels of tumors from 277 lung cancer patients that underwent curative intent surgery. PD-L1 was identified as a prognostic factor, depending on histologic subtype. Abstract The programmed death-ligand 1 (PD-L1) plays a crucial role in immunomodulatory treatment concepts for end-stage non-small cell lung cancer (NSCLC). To date, its prognostic significance in patients with curative surgical treatment but regional nodal metastases, reflecting tumor spread beyond the primary site, is unclear. We evaluated the prognostic impact of PD-L1 expression in a surgical cohort of 277 consecutive patients with pN1 NSCLC on a tissue microarray. Patients with PD-L1 staining (clone SP263) on >1% of tumor cells were defined as PD-L1 positive. Tumor-specific survival (TSS) of the entire cohort was 64% at five years. Low tumor stage (p < 0.0001) and adjuvant therapy (p = 0.036) were identified as independent positive prognostic factors in multivariate analysis for TSS. PD-L1 negative patients had a significantly better survival following adjuvant chemotherapy than PD-L1 positive patients. The benefit of adjuvant therapy diminished in patients with PD-L1 expression in more than 10% of tumor cells. Stratification towards histologic subtype identified PD-L1 as a significant positive predictive factor for TSS after adjuvant therapy in patients with adenocarcinoma, but not squamous cell carcinoma. Routine PD-L1 assessment in curative intent treatment may help to identify patients with a better prognosis. Further research is needed to elucidate the predictive value of PD-L1 in an adjuvant setting.