Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of Anaplasma phagocytophilum in European brown hares (Lepus europaeus) using three different methods

European brown hare (Lepus europaeus Pallas 1778) is a broadly distributed lagomorph species in Europe, recognized as a host for Ixodes ricinus and reservoir of a wide range of pathogens with zoonotic potential. Even though Lepus europaeus represents an important game animal in Central Europe, the data available on Anaplasma phagocytophilum in this lagomorph are scarce. In this study, three populations of brown hare from distinct localities in the Czech Republic were analysed for the presence of Anaplasma phagocytophilum DNA. We used standard qPCR, targeting the msp2 gene and adapted the same assay also for digital droplet PCR. Out of 91 samples, these two methods identified 9 and 12 as positive, respectively. For taxonomic analysis, we amplified the groEL gene from five of six samples that were found positive by both methods. In phylogenetic analyses, this haplotype belongs to ecotype 1, and to the subclade with isolates from cervids and I. ricinus. Our findings underline the importance of correct result interpretation and positivity cut‐off set‐up for different detection methods of A. phagocytophilum. This bacterium is characterized by a high intraspecific variability and highly sensitive detection itself, is not enough. Detailed molecular typing is necessary to define the zoonotic potential of different strains and their natural reservoirs.
Comparative Assessment of Diagnostic Homologous Recombination Deficiency–Associated Mutational Signatures in Ovarian Cancer

Purpose: Homologous recombination (HR) deficiency (HRD) is one of the key determinants of PARP inhibitor response in ovarian cancer, and its accurate detection in tumor biopsies is expected to improve the efficacy of this therapy. Because HRD induces a wide array of genomic aberrations, mutational signatures may serve as a companion diagnostic to identify PARP inhibitor–responsive cases. Experimental Design: From the The Cancer Genome Atlas (TCGA) whole-exome sequencing (WES) data, we extracted different types of mutational signature–based HRD measures, such as the HRD score, genome-wide LOH, and HRDetect trained on ovarian and breast cancer–specific sequencing data. We compared their performance to identify BRCA1/2-deficient cases in the TCGA ovarian cancer cohort and predict survival benefit in platinum-treated, BRCA1/2 wild-type ovarian cancer. Results: We found that the HRD score, which is based on large chromosomal alterations alone, performed similarly well to an ovarian cancer–specific HRDetect, which incorporates mutations on a finer scale as well (AUC = 0.823 vs. AUC = 0.837). In an independent cohort these two methods were equally accurate predicting long-term survival after platinum treatment (AUC = 0.787 vs. AUC = 0.823). We also found that HRDetect trained on ovarian cancer was more accurate than HRDetect trained on breast cancer data (AUC = 0.837 vs. AUC = 0.795; P = 0.0072). Conclusions: When WES data are available, methods that quantify only large chromosomal alterations such as the HRD score and HRDetect that captures a wider array of HRD-induced genomic aberrations are equally efficient identifying HRD ovarian cancer cases.
Controversies in EUS: Do we need miniprobes?

This is the fifth in a series of papers entitled “Controversies in EUS. ” In the current paper, we deal with high-resolution catheter probes, otherwise known as EUS miniprobes (EUS-MPs). The application of miniprobes for early carcinomas in the entire intestinal tract, for subepithelial lesions, and for findings in the bile duct and pancreatic duct as well as endobronchial use is critically discussed. Submucous lesions, especially in the colon, but also early carcinomas in special cases are considered the most important indications. The argument is illustrated by numerous examples.
Biomarker Analysis of the Phase III NALA Study of Neratinib + Capecitabine versus Lapatinib + Capecitabine in Patients with Previously Treated Metastatic Breast Cancer

Purpose: Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + capecitabine (L+C) in 621 patients with HER2-positive (HER2+) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens in the metastatic setting. We evaluated correlations between exploratory biomarkers and PFS. Patients and Methods: Somatic mutations were evaluated by next-generation sequencing on primary or metastatic samples. HER2 protein expression was evaluated by central IHC, H-score, and VeraTag/HERmark. p95 expression (truncated HER2) was measured by VeraTag. HRs were estimated using unstratified Cox proportional hazards models. Results: Four hundred and twenty samples had successful sequencing: 34.0% had PIK3CA mutations and 5.5% had HER2 (ERBB2) mutations. In the combined patient populations, PIK3CA mutations trended toward shorter PFS [wild-type vs. mutant, HR = 0.81; 95% confidence interval (CI), 0.64–1.03], whereas HER2 mutations trended toward longer PFS [HR = 1.69 (95% CI, 0.97–3.29)]. Higher HER2 protein expression was associated with longer PFS [IHC 3+ vs. 2+, HR = 0.67 (0.54–0.82); H-score ≥240 versus <240, HR = 0.77 (0.63–0.93); HERmark positive vs. negative, HR = 0.76 (0.59–0.98)]. Patients whose tumors had higher HER2 protein expression (any method) derived an increased benefit from N+C compared with L+C [IHC 3+, HR = 0.64 (0.51–0.81); H-score ≥ 240, HR = 0.54 (0.41–0.72); HERmark positive, HR = 0.65 (0.50–0.84)], as did patients with high p95 [p95 ≥2.8 relative fluorescence (RF)/mm2, HR = 0.66 (0.50–0.86) vs. p95 < 2.8 RF/mm2, HR = 0.91 (0.61–1.36)]. Conclusions: PIK3CA mutations were associated with shorter PFS whereas higher HER2 expression was associated with longer PFS. Higher HER2 protein expression was also associated with a greater benefit for N+C compared with L+C.
Mental health and discrimination among migrants from Africa: An Italian cross‐sectional study

Abstract This study aimed to assess depression, anxiety, posttraumatic stress disorder (PTSD) and discrimination in African migrants and investigate determinants. A cross‐sectional study was conducted in Italy (July 2019–February 2020). Inclusion criteria: being a citizen of an African country or having parents who are citizens of an African country. Questionnaires included tests for depression, anxiety, PTSD, discrimination. Multivariable regressions were performed. Participants were 293. The prevalence of depression, anxiety, and PTSD was: 12.1%, 12.1%, and 24.4%. Only 7.2% declared not to be discriminated. Among significantly associated factors, waiting for/being in possession of temporary permits and discrimination were associated with all mental outcomes. Being (or having parents from) Sub‐Saharan Africa increased the likelihood of discrimination. A relevant prevalence of mental illnesses was reported. Particularly, Sub‐Saharan Africans potentially offer a unique point of view. Migrants' mental health should be a priority for national and international programs of health monitoring.
Understanding Online Health Risk Information Seeking and Avoiding during the COVID-19 Pandemic

ABSTRACT This study tested the utility of the Risk Information Seeking and Processing (RISP) model in understanding why people seek or avoid online information about COVID-19. Data collected at three different time points (i.e., February, April, and May 2020) showed the measured RISP model constructs explained between 70–78.8% of the variance for information seeking, and between 36.9–62.5% of the variance for information avoiding. Specifically, fear, information insufficiency, and relevant channel beliefs consistently predicted information seeking. Further, information insufficiency and relevant channel beliefs consistently predicted information avoidance. However, fear had no association with information avoidance. Longitudinally, the study found that within individuals, there were larger increases in most RISP model constructs between Time 1 and Time 2, and smaller changes occurred from Time 2 to Time 3. However, there was no significant change in information seeking over time.
Inter‐subject stability and regional concentration estimates of 3D‐FID‐MRSI in the human brain at 7 T

Recently, a 3D‐concentric ring trajectory (CRT)‐based free induction decay (FID)‐MRSI sequence was introduced for fast high‐resolution metabolic imaging at 7 T. This technique provides metabolic ratio maps of almost the entire brain within clinically feasible scan times, but its robustness has not yet been thoroughly investigated. Therefore, we have assessed quantitative concentration estimates and their variability in healthy volunteers using this approach.
Molecular characterization of Staphylococcus aureus isolates derived from severe pneumonia: a retrospective monocentre study

Abstract Background Staphylococcus aureus is endowed with a repertoire of virulence factors potentially implicated in its pathogenicity and ability to cause invasive disease. The main objective of this study was to describe the bacterial genotype, including virulence genes and affiliation to clonal complexes (CCs), encountered in severe pneumonia. Methods DNA microarray was used to analyse 18 S. aureus isolates from patients hospitalized with severe pneumonia between 2017 and 2019. Results Among 18 S. aureus isolates, 14 were methicillin-susceptible S. aureus (MSSA), and 4 methicillin-resistant S. aureus (MRSA). There were 14 community-acquired, 3 healthcare-associated, and 1 hospital-acquired infections. Different radiological presentations were observed: necrotizing pneumonia (n = 8, 44%), alveolar consolidation (n = 7, 39%), alveolar-interstitial infiltrates (n = 3, 17%). Sixteen patients (89%) required ICU hospitalization, 13 (72%) an invasive mechanical ventilation, and 12 (67%) a vasopressor support. Mortality affected 6 patients (33%). Panton–Valentine leukocidin (PVL), staphylococcal enterotoxins, toxic shock syndrome toxine-1 (TSST-1) encoding genes were documented in nine (50%), 12 (67%), one (6%) of the isolates, respectively. Accessory regulator gene group I was the most reported (n = 9, 50%) and was found in five deaths. The majority of isolates were affiliated to CC152 (n = 6), followed by CC15 (n = 3), CC45 (n = 2), CC30 (n = 2), CC1 (n = 2), CC8 (n = 1), CC9 (n = 1), and CC25 (n = 1). All the CC152 isolates were PVL-positive. Conclusion CC152-PVL positive S. aureus strains were the most prevalent in severe pneumonia. Other virulence gene profiles were found coupled to additional clonal lineages. A genotyping strategy contributes to describe the current circulating strains and bacterial genetic backgrounds.
Dendrite Morphology Minimally Influences the Synaptic Distribution of Excitation and Inhibition in Retinal Direction-Selective Ganglion Cells

Abstract Throughout the nervous system, the organization of excitatory and inhibitory synaptic inputs within a neuron’s receptive field shapes its output computation. In some cases, multiple motifs of synaptic organization can contribute to a single computation. Here, we compare two of these mechanisms performed by two morphologically distinct retinal direction-selective ganglion cells (DSGCs): directionally tuned inhibition and spatially offset inhibition. Using drifting stimuli, we found that DSGCs that have asymmetric dendrites exhibited stronger directionally tuned inhibition than symmetric DSGCs. Using stationary stimuli to map receptive fields, we found that DSGCs with both symmetric and asymmetric dendrites exhibited similar spatially offset inhibition. Interestingly, we observed that excitatory and inhibitory synapses for both cell types were locally correlated in strength. This result indicates that in the mouse retina, dendritic morphology influences the amount of tuned inhibition attained through asymmetric wiring but does not dictate the synaptic organization of excitation relative to inhibition.
Microbiological Pattern, Antimicrobial Resistance and Prevalence of MDR/XDR Organisms in Patients With Diabetic Foot Infection in an Indian Tertiary Care Hospital

Foot infections are the most prevalent problem in persons with diabetes. The burden of multidrug resistant (MDR) microorganisms in diabetic foot infections (DFIs) is rising day by day. Given that, the present study aims to determine the variety of microorganisms isolated from the diabetic foot ulcers (DFUs), and their antibiotic sensitivity pattern. This prospective observational study was conducted for 1 year at Bharati Hospital and Research Centre, Pune, India. Clinically infected patients with DFU admitted to the surgery ward were included in this study. The specimen for microbiological studies is obtained from the wound swabs, soft tissue, and bone tissue as a part of routine clinical care. All demographic, clinical data, microbial culture results were collected, and evaluated for each case. Antimicrobial susceptibility testing to different agents was carried out using the VITEK-2® machine. A total of 110 microorganisms were isolated from 76 specimens, with an average of 1.4 organisms per lesion. Staphylococcus aureus (n = 27, 24.5%) and Escherichia coli (n = 17, 15.4%) were the most prevalent Gram-positive and Gram-negative organisms isolated, respectively. MDR organisms constituted up to 52 (47.2%), while 6 (5.4%) of the samples were extensively drug resistant (XDR). Methicillin-resistant S aureus (MRSA) accounted for up to 19 (70.3%) of the S aureus isolates, likewise extended-spectrum beta-lactamase producing microorganisms constituted 16 (14.5%) of total isolates in this study. Oxacillin and benzyl penicillin exhibited least susceptibility against Gram-positive bacteria, among Gram-negative organisms; cefuroxime, ceftriaxone, and ciprofloxacin were least sensitive. As most of the S aureus isolate in our study was MRSA, empirical antimicrobial therapy may include coverage for MRSA in a patient with risk factors associated with this pathogen. A crucial observation is the presence of XDR strains of Proteus mirabilis in DFIs, which is resistant to almost all the antimicrobials, tested. Appropriate antimicrobial selection may reduce the morbidity and the emergence of MDR organisms in DFIs.
Dual Function Antibody Conjugates for Multimodal Imaging and Photoimmunotherapy of Cancer Cells

Precision imaging, utilizing molecular targeted agents, is an important tool in cancer diagnostics and guiding therapies. While there are limitations associated with single mode imaging probes, multimodal molecular imaging probes enabling target visualization through complementary imaging technologies provides an attractive alternative. However, there are several challenges associated with designing molecular probes carrying contrast agents for complementary multimodal imaging. Here, we propose a dual function antibody conjugate (DFAC) comprising an FDA approved photosensitizer Benzoporphyrin derivative (BPD) and a naphthalocyanine‐based photoacoustic dye (SiNc(OH)) for multimodal infrared (IR) imaging. While fluorescence imaging, through BPD, provides sensitivity, complementing it with photoacoustic imaging, through SiNc(OH), provides a depth‐resolved spatial resolution much beyond the optical diffusion limits of fluorescence measurements. Through a series of in vitro experiments, we demonstrate the development and utilization of DFACs for multimodal imaging and photodynamic treatment of squamous cell carcinoma (A431) cell line. The proposed DFACs have potential use in precision imaging applications such as guiding tumor resection surgeries and photodynamic treatment of residual microscopic disease thereby minimizing local recurrence. The data demonstrated in this study merits further investigation for its preclinical and clinical translation.
Hemodynamic and Functional Correlates of Concentric versus Eccentric LVH in a Community-Based Sample with Prevalent Volume-Dependent Hypertension.

BACKGROUND Whether in populations with prevalent volume-dependent primary hypertension, concentric left ventricular (LV) remodelling beyond hypertrophy (LVH) represents the impact of a pressure rather than a volume overload, is unclear. METHODS Using central arterial pressure, and aortic velocity and diameter measurements in the outflow tract and echocardiography, we determined the factors that associate with concentric LVH or remodelling in the LV short axis in a community of African ancestry (n=709) with prevalent volume-dependent primary hypertension. RESULTS Both left ventricular mass index (LVMI) and RWT were positively and independently associated with end diastolic volume (EDV), stroke volume (SV) and peak aortic flow (Q) (p<0.05 to <0.0001). However, neither LVMI nor RWT were positively and independently associated with systemic vascular resistance (SVR), or aortic characteristic impedance (Zc) or inversely associated with total arterial compliance (TAC). Consequently, both concentric (p<0.0001) and eccentric (p<0.0001) LVH were associated with similar increases in EDV, SV, and either office brachial, central arterial or 24-hour blood pressures, but neither increases in SVR or Zc nor decreases in TAC. Left ventricular RWT, but not LVMI was nevertheless independently and inversely associated with myocardial systolic function (midwall fractional shortening and LV wall myocardial shortening velocity [s']) (p<0.05 to <0.005) and decreases in LV systolic function were noted in concentric (p<0.05), but not eccentric LVH. CONCLUSIONS In volume-dependent primary hypertension, concentric LVH is determined as much by volume-dependent increases in systemic flow and an enhanced BP as eccentric LVH. Concentric remodelling nevertheless reflects decreases in systolic function beyond LVH.
Investigation of changes in activity and function in acute unilateral open globe injury–associated brain regions based on percent amplitude of fluctuation method: a resting-state functional MRI study

Background Open globe injury (OGI) is a serious condition that can lead to visual impairment and lifelong sequelae, brain activity of some brain regions would change in patients with OGI. Purpose To evaluate changes in brain activity associated with unilateral OGI by resting-state functional magnetic resonance imaging (rs-fMRI) and analysis of percentage amplitude of fluctuation (PerAF). Material and Methods A total of 22 patients with OGI (12 men, 10 women) and 22 healthy controls (HCs) matched for sex, age, and body weight were enrolled. All patients underwent rs-fMRI scans. Brain activity in the relevant brain regions was assessed with the PerAF method. The ability of PerAF to distinguish patients with OGI from HCs was assessed by receiver operating characteristic (ROC) curve analysis. We also examined the relationship between Hospital Anxiety and Depression Scale (HADS) scores and PerAF signals by Pearson’s correlation analysis. Results PerAF values in amygdala_R and Frontal_Inf_Orb_L/Frontal_Inf_Oper_L were increased whereas that in Cerebellum Anterior Lobe/Cerebelum_8_L was decreased in patients with OGI compared to HCs. The areas under the ROC curve showed that these brain regions could distinguish between patients with OGI and HCs. The PerAF value of amygdala_R was positively correlated with HADS scores. Conclusion Changes in PerAF in the amygdala_R, Frontal_inferior_Orb_L/Frontal_Inf_Oper_L, and Cerebellum Anterior Lobe/Cerebelum_8_L in patients with OGI may be related to an increased risk of developing psychiatric disorders such as anxiety and depression. PerAF can be used to investigate the neural basis of complications associated with OGI and monitor disease progression.
Child sexual abuse in India: A wake-up call

The World Health Organization (WHO) defines Child Sexual Abuse (CSA) as “the involvement of a child in sexual activity that he or she does not fully comprehend, is unable to give informed consent to, or for which the child is not developmentally prepared and cannot give consent, or that violates the laws or social taboos of society. ”[1] In India, the Protection of Children from Sexual Offences (POCSO) Act, 2012 (that regards any sexual activity with a child below 18 years a crime) describes various forms of sexual offenses. [2] CSA includes an array of sexual activities like fondling, inviting a child to touch or be touched sexually, intercourse, exhibitionism, involving a child in prostitution or pornography, or online child luring by cyber-predators. [3,4] Because of the sensitive and taboo nature of the issue, it is extremely difficult to access this population of victims of CSA for research. It is affected by socio-cultural traditions and often goes unreported, as a culture of privacy, fear of indignity, and social humiliation prevent the disclosure of such crimes. [5] Also, certain forms of CSA, namely, like touching, fondling of child’s genitals, or breasts are wrongly perceived as minor types and are often ignored.
Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis

Background and Objectives To assess whether plasma neurofilament light chain (NfL) levels are elevated before amyotrophic lateral sclerosis (ALS) diagnosis and to evaluate whether prediagnostic NfL levels are associated with metabolic alterations. Methods We conducted a matched case–control study nested in 3 large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study) and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels. Results Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 SD increase 2.68, 95% CI 1.18–6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI 0.78–1.73). A total of 21 metabolites were correlated with prediagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments. Discussion Plasma NfL levels were elevated in prediagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease. Classification of Evidence This study provides Class II evidence that plasma NfL levels are elevated in prediagnostic ALS.