Miracle-dz/UniFAR-FTUs huggingface dataset:
Conserved organ-specific microbial assemblages in different populations of a terrestrial crab

Microorganisms are ubiquitous in the environment and provide genetic and physiological functions to multicellular organisms. Knowledge on the associated microbiota is becoming highly relevant to understand the host’s ecology and biology. Among invertebrates, many examples of endosymbiosis have been described, such as those in corals, ants, and termites. At present, however, little is known on the presence, diversity, and putative roles of the microbiota associated to brachyuran crabs in relation to their environment. In this work we investigated the associated microbiota of three populations of the terrestrial brachyuran crab Chiromantes haematocheir to find evidence of a conserved organ-specific microbiome unrelated to the population of origin and dissimilar from environmental microbial assemblages. Bacterial 16S rRNA gene and fungal ITS sequences were obtained from selected crab organs and environmental matrices to profile microbial communities. Despite the presence of truly marine larval stages and the absence of a gregarious behaviour, favouring microbiota exchanges, we found common, organ-specific microbiota, associated with the gut and the gills of crabs from the different populations (with more than 15% of the genera detected specifically enriched only in one organ). These findings suggest the presence of possible functional roles of the organ-specific microbiota.
Nuclear envelope budding is a response to cellular stress

Significance A defining feature of eukaryotes is the nuclear envelope, a double lipid bilayer that serves to isolate and protect the cell’s genetic material. Transport of large molecules over this barrier is believed to occur almost exclusively via the nuclear pores. However, herpes virions and mega-ribonucleoproteins (megaRNPs) use an alternative means of transport—via nuclear envelope budding (NEB). Here, we show NEB is a ubiquitous eukaryotic phenomenon and increases when exposed to various forms of cellular stress. NEB frequency was maximal when the cell was challenged with a drug that induces protein misfolding, indicating this transport pathway plays a role in protein quality control. These results imply that NEB is an underappreciated yet potentially fundamental means of nuclear transport. Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex. Through quantitative electron microscopy and tomography, we demonstrate how NEB is evolutionarily conserved from early protists to human cells. In the yeast Saccharomyces cerevisiae, NEB events occur with higher frequency during heat shock, upon exposure to arsenite or hydrogen peroxide, and when the proteasome is inhibited. Yeast cells treated with azetidine-2-carboxylic acid, a proline analog that induces protein misfolding, display the most dramatic increase in NEB, suggesting a causal link to protein quality control. This link was further supported by both localization of ubiquitin and Hsp104 to protein aggregates and NEB events, and the evolution of these structures during heat shock. We hypothesize that NEB is part of normal cellular physiology in a vast range of species and that in S. cerevisiae NEB comprises a stress response aiding the transport of protein aggregates across the nuclear envelope.
Successful and unsuccessful bioaugmentation experiments monitored by fluorescent in situ hybridization

Two nitrifying reactors were operated under the same conditions except that one was twice inoculated with the aerobic denitrifying bacteria Microvirgula aerodenitrificans . The first bioaugmentation induced a transient nitrogen loss. Fluorescent in situ hybridization revealed that the bioaugmented bacteria had been rapidly eaten by protozoa. The second massive inoculation unbalanced the ecosystem and resulted in an overgrowth of protozoa and perturbations of nitrification, whereas both parameters remained stable in the non bioaugmented reactor. To enhance the incorporation of the added bacteria to indigenous flocs, two strategies were then tested. First, coagulating and flocculating substances were added to the reactor just after bioaugmentation and second, the bacteria were embedded in alginate beads before inoculation. The latter strategy gave the best results. After break-up of the beads, alginate fragments, containing microcolonies of M. aerodenitrificans , were found to be incorporated into the existing flocs. Alginate beads offer a temporary protection against grazing and favor the adhesion of the exogenous bacterial microcolonies to the existing flocs. These beads therefore constitute a suitable bioaugmentation vector to incorporate a bacterial strain into activated sludge flocs.
Prevalence of Macroprolactin in Hyperprolactinemic patients receiving Anti-psychotics

Background: Prolactin (PRL) hormone circulates in the blood in three forms, mono-prolactin which constitutes 85 % of prolactin in healthy and hyperprolactinemia conditions, a dimeric prolactin (big PRL) and polymeric PRL (big-big prolactin or Macroprolactin). Macroprolactin in normal conditions is not exceeding 2% of the total serum prolactin and had no biological activity. In some cases, of hyperprolactinemia the dominant form becomes MaPRL and exceeding the 2% percentage of total leading to misdiagnosis of hyperprolactinemia and un-necessary radiological investigations. The aim of this study is to detect the prevalence of MaPRL in Psychiatric patients with hyperprolactinemia due to anti-psychotic medications at Al Masarra hospital. Material and methods: The study was conducted on 190 samples from patients with high prolactin in Al Masarra Hospital either inpatients or out-patient clinics either male or non-lactating not pregnant female. The measurement of Prolactin level was measured by the automated analyser COBAS e411, Roche Diagnostic. Macroprolactin was precipitated by using Polyethylene glycol (PEG). Results: Prevalence of Macroprolactin was 10.5 % of hyperprolactinemic patients receiving antipsychotics. There was a statistically significant difference in gender between the symptomatic and asymptomatic group. There was no significant difference in medications used between the symptomatic and asymptomatic group and there was a statistically significant difference in total Prolactin & Macroprolactin between males and females. Conclusions: Investigation for Macroprolactin should be done in every hyperprolactinemia patient who is receiving antipsychotics more especially the asymptomatic cases to avoid unnecessary radiological imaging and treatment.
COVID-19: A comparative study of severity of patients hospitalized during the first and the second wave in South Africa.

Abstract Background South Africa has experienced two waves of COVID-19 infections, the second of which was inter alia attributed to the emergence of a novel SARS-CoV2 variant, 501Y.V2. This variant possibly has increased virulence and may be associated with increased mortality. The objective of this study was to determine if patients admitted in the second wave had more severe illness and higher mortality than those admitted in the first. Methods We analysed and compared the characteristics, biological severity markers, treatments, level of care and outcomes of patients hospitalised in a private hospital in the Eastern Cape Province, South Africa. Results Compared to the first wave, patients admitted in the second were older and less likely to have co-morbidities. In contrast, the D-dimer and interleukin-6 (IL-6) levels were significantly higher. Despite this, significantly less patients were admitted to ICU and/or were mechanically ventilated. The total length of hospital stay was identical in both groups. Whereas the overall mortality was not significantly higher during the second wave, the ICU mortality was. Those that died in the second wave were older than those in the first wave. Multivariable logistic regression showed that being admitted during the second wave was an independent risk factor for mortality. Conclusion This study appears to confirm previous reports that the 501Y.V2 variant is possibly more virulent as indicated by the higher levels of D-dimer and IL-6, the slight increase in mortality of hospitalised patients and the higher ICU mortality in the second wave.
First-in-Human Phase I Study of Envafolimab, a Novel Subcutaneous Single-Domain Anti-PD-L1 Antibody, in Patients with Advanced Solid Tumors.

LESSONS LEARNED Subcutaneous injection was an effective route of administration for envafolimab with a favorable pharmacokinetic profile in patients with previously treated advanced solid tumors Subcutaneous envafolimab was well tolerated and had durable antitumor activity at a wide range of doses and schedules Envafolimab has the potential to be a more convenient option than currently approved intravenous PD-1/PD-L1 inhibitors BACKGROUND: Envafolimab is a novel fusion of a humanized single-domain PD-L1 antibody and human IgG1 Fc fragment formulated for subcutaneous injection. This study explored the safety and feasibility of subcutaneous administration of envafolimab as an alternative to intravenous administration of PD-1/PD-L1 inhibitors in the treatment of advanced, refractory solid tumors. METHODS This was a first-in-human, open-label phase I trial. In a dose-escalation phase, patients received subcutaneous envafolimab 0.01-10 mg/kg once weekly following a modified 3+3 design. In a dose-exploration phase, patients received subcutaneous envafolimab 300 mg once every 4 weeks. RESULTS Twenty-eight patients were enrolled (dose escalation n = 18, dose exploration n = 10, median age 66 years; 71% male; ECOG performance score = 0 [21%] or 1 [79%]). No dose-limiting toxicities or injection-site reactions were reported. Envafolimab demonstrated dose-proportional increases in area under the time-concentration curve and maximum plasma concentration. Median time to maximum plasma concentration was 4-7 days. In the dose-exploration phase, terminal half-life was 14 days after dose 1 in cycle 1 and 23 days at steady state. Three patients experienced a confirmed partial response. CONCLUSION Subcutaneous envafolimab had a favorable safety and pharmacokinetic profile, with promising preliminary antitumor activity in patients with advanced solid tumors.
COVID-19 induces lower levels of IL-8, IL-10, and MCP-1 than other acute CRS-inducing diseases

Xue Zhang Kang et al. (1) investigate the relations between the cytokine release syndrome (CRS), cytokines, and dif-ferent acute diseases that cause CRS. Their study finds strikingly elevated levels of four proinflammatory cytokines, including IL-6, IL-8, IL-10, and MCP-1, in 91 patients with CRS associated with sepsis, acute respiratory distress syndrome (ARDS), or burns. Further-more, the elevated levels of these cytokines are positively correlated with the increasing expression of the coagulation cascade activator plasminogen activator inhibitor-1 (PAI-1). PAI-1 is capable of causing small blood clots in blood vessels throughout the body (including pulmonary blood vessels). Impor-tantly, the increase of PAI-1 is associated with more severe pneumonia, a common cause of death in COVID-19 patients. Finally, they find that the treat-ment with tocilizumab, a human monoclonal antibody that blocks IL-6 signal transduction, decreases the PAI-1 levels and alleviates severe respiratory complica-tions in COVID-19 patients. We agree with their views on the function of IL-6 and PAI-1 in CRS. Kang et al. (1) also observe an important clinical characteristic: that the cytokines IL-6, IL-8, IL-10, and MCP-1, in the plasma of severe COVID-19 patients, are not as high as those in CRS patients with sepsis, ARDS, and burns. However, the authors did not perform statistical tests to directly investigate the associations between COVID-19 and these cytokines, which prompted us to statistically
Bilateral diffuse uveal melanocytic proliferation with multifocal diffuse integumentary melanocytic proliferation paraneoplastic syndrome: A case report

Bilateral diffuse uveal melanocytic proliferation (B‐DUMP) is a rare paraneoplastic syndrome typically presenting with bilateral visual loss. B‐DUMP is associated with extraocular systemic malignancies with the most common being lung cancer in males and uro‐gynaecological cancer in females (mainly ovarian cancer). Cutaneous and/or mucosal involvement in patients with B‐DUMP has been reported but it is not well characterised. Herein, we present a female in her 70s with diagnosis of stage IV vaginal clear‐cell carcinoma and metastatic melanoma of unknown primary that developed progressive bilateral loss of visual acuity compatible with ‘B‐DUMP’. Simultaneously, she developed multifocal bilateral bluish‐greyish patches on the skin that were shown to have a proliferation of dermal melanocytes. We propose that the clinical and histopathologic cutaneous findings seen in patients with B‐DUMP be termed ‘diffuse integumentary melanocytic proliferation (DIMP)’.
Heritable disorders of oxygen sensing

Hypoxia‐inducible factors (HIFs) activate gene transcription in response to reduced O2 availability and play critical roles in development, physiology, and disease pathogenesis. Mutations that dysregulate HIF activity are the genetic basis for tumor predisposition in the von Hippel–Lindau syndrome and excess red blood cell production in hereditary erythrocytosis.
A three-dimensional measurement based on CT for the posterior tilt with ideal inter-and intra-observer reliability in non-displaced femoral neck fractures

Abstract Posterior tilt is associated with prognosis of non-displaced femoral neck fractures (FNFs). Knowledge of their association is critical and informs surgeons whether to choose internal fixation or arthroplasty in treatment of non-displaced FNFs. This study aimed to design a novel three-dimensional (3D) posterior tilt measurement and evaluate the intra- and inter-observer variability compared to two-dimensional (2D) measurement proposed by Palm. We hypothesized that 3D measurement would be more accurate and realistic with higher reliability. To test the hypothesis, three observers measured the posterior tilt on the radiographs of 50 non-displaced FNFs, twice with both methods. Intra- and inter-observer reliability for each measurement method used were determined. The measured angle was divided into two categories, at the cut-off of 20° for clinical practice simulation. Intra- and inter-observer reliability were identified for clinical effectiveness. The results indicated that inter- and intra-observer reliability for 3D measurement and its classification was almost perfect with an intraclass coefficient of 0.995 (0.994) and a kappa value of 0.927(0.947), respectively. Conversely, a substantial inter- and intra-observer reliability for the 2D measurement was obtained with an interclass coefficient of 0.764 as well as an intraclass coefficient of 0.773. The clinical validity for 2D measurement showed slight inter-reliability and moderate intra-reliability with a kappa value of 0.192 and 0.587, respectively. Hence, the novel 3D measurement appears to be more reliable with a strong inter- and intra-observer reliability measurement. Further clinical studies are needed to carry out to validate this hypothesis.
Infantile orbital abscess: clinical presentation, microbiological profile, and management outcomes

ABSTRACT Purpose Orbital abscesses in children are not uncommon. Unless managed in a timely fashion, they can potentially lead to vision-threatening as well as life-threatening complications. The objective of this study is to report the clinical and microbiological profile and management outcomes in infants presenting with orbital abscesses. Materials and Methods A retrospective review of electronic medical records of children younger than 1 year with a diagnosis of an orbital abscess was done. The data was collected from a time period of 12 years (2007–2019). The data collected included mode of presentation, radiological, microbiological and histopathological features, and the final outcome. Results A total of nine patients met the inclusion criteria. The mean age at presentation was 19 weeks. Three patients had upper respiratory tract infection, one had a congenital nasolacrimal duct obstruction, two had sinusitis, and one patient had neonatal sepsis. All patients underwent imaging following which abscess drainage was performed. Methicillin-sensitive Staphylococcus aureus was the most common organism, which was isolated in five patients, Methicillin-resistant S. aureus was isolated in three, while one patient had Entomophthorales fungal infection. The median follow-up period was 10 months (range 5 days to 89 months). There was no recurrence in the cohort. At least one patient had visual impairment at the last follow up. Conclusion Orbital abscesses in infants are rare. Imaging and prompt drainage of the abscess supplemented by appropriate antimicrobial regimen leads to a successful outcome.
Ancient horse genomes reveal the timing and extent of dispersals across the Bering Land Bridge

The Bering Land Bridge (BLB) last connected Eurasia and North America during the Late Pleistocene. Although the BLB would have enabled transfers of terrestrial biota in both directions, it also acted as an ecological filter whose permeability varied considerably over time. Here we explore the possible impacts of this ecological corridor on genetic diversity within, and connectivity among, populations of a once wide‐ranging group, the caballine horses (Equus spp.). Using a panel of 187 mitochondrial and eight nuclear genomes recovered from present‐day and extinct caballine horses sampled across the Holarctic, we found that Eurasian horse populations initially diverged from those in North America, their ancestral continent, around 1.0–0.8 million years ago. Subsequent to this split our mitochondrial DNA analysis identified two bidirectional long‐range dispersals across the BLB ~875–625 and ~200–50 thousand years ago, during the Middle and Late Pleistocene. Whole genome analysis indicated low levels of gene flow between North American and Eurasian horse populations, which probably occurred as a result of these inferred dispersals. Nonetheless, mitochondrial and nuclear diversity of caballine horse populations retained strong phylogeographical structuring. Our results suggest that barriers to gene flow, currently unidentified but possibly related to habitat distribution across Beringia or ongoing evolutionary divergence, played an important role in shaping the early genetic history of caballine horses, including the ancestors of living horses within Equus ferus.
Associations between visual hallucinations and impaired visuo-spatial abilities in dementia with Lewy bodies.

Objectives: In dementia with Lewy bodies (DLB) recurrent visual hallucinations (VH) often coexist or occur consecutively to impaired visual perception. Since in-depth neuropsychological testing is time-consuming, and therefore, not routinely performed in clinical settings, we aimed to explore whether standard cognitive screening tests may be helpful to alert a clinician to the presence of VH in DLB by exploring association between visuo-spatial dysfunction and VH. Method: The clock drawing, cube, and pentagons copying items from Montreal Cognitive Assessment and Mini-Mental State Exam and nonmotor Hooper visual organization test (HVOT) have been scored in DLB patients with and without VH using traditional and extended scoring methods. Results: Forty-five of 69 (65%) DLB patients were VH-positive (VH+). VH+ patients performed worse on the clock drawing (8.8/16 vs. 11.9/16, p = .016) with a higher rate of misrepresentation of time (69% vs. 29%, p = .002) and numbers (53% vs. 25%, p = .024). Likewise, VH+ patients performed worse on the HVOT (13.3/30 vs. 15.7/30, p = .009) having more isolated (6.2/30 vs. 4.4/30, p = .012) types of responses compared to VH- patients. Both groups had similar copying ability (p > .05). The VH discriminative accuracy of the clock drawing was comparable to that of the more elaborate test of visual perception, the HVOT. Conclusions: In DLB impaired drawing and visual organization, but not copying ability is associated with the presence of VH. The simple clock drawing test can be helpful to alert a clinician to the possibility of VH in DLB. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Differential drivers of intraspecific and interspecific competition during malaria–helminth co-infection

Graphical abstract Abstract Various host and parasite factors interact to determine the outcome of infection. We investigated the effects of two factors on the within-host dynamics of malaria in mice: initial infectious dose and co-infection with a helminth that limits the availability of red blood cells (RBCs). Using a statistical, time-series approach to model the within-host ‘epidemiology’ of malaria, we found that increasing initial dose reduced the time to peak cell-to-cell parasite propagation, but also reduced its magnitude, while helminth co-infection delayed peak cell-to-cell propagation, except at the highest malaria doses. Using a mechanistic model of within-host infection dynamics, we identified dose-dependence in parameters describing host responses to malaria infection and uncovered a plausible explanation of the observed differences in single vs co-infections. Specifically, in co-infections, our model predicted a higher background death rate of RBCs. However, at the highest dose, when intraspecific competition between malaria parasites would be highest, these effects of co-infection were not observed. Such interactions between initial dose and co-infection, although difficult to predict a priori, are key to understanding variation in the severity of disease experienced by hosts and could inform studies of malaria transmission dynamics in nature, where co-infection and low doses are the norm.
Connectivity within regions characterizes epilepsy duration and treatment outcome

Finding clear connectome biomarkers for temporal lobe epilepsy (TLE) patients, in particular at early disease stages, remains a challenge. Currently, the whole‐brain structural connectomes are analyzed based on coarse parcellations (up to 1,000 nodes). However, such global parcellation‐based connectomes may be unsuitable for detecting more localized changes in patients. Here, we use a high‐resolution network (~50,000‐nodes overall) to identify changes at the local level (within brain regions) and test its relation with duration and surgical outcome. Patients with TLE (n = 33) and age‐, sex‐matched healthy subjects (n = 36) underwent high‐resolution (~50,000 nodes) structural network construction based on deterministic tracking of diffusion tensor imaging. Nodes were allocated to 68 cortical regions according to the Desikan–Killany atlas. The connectivity within regions was then used to predict surgical outcome. MRI processing, network reconstruction, and visualization of network changes were integrated into the NICARA (https://nicara.eu). Lower clustering coefficient and higher edge density were found for local connectivity within regions in patients, but were absent for the global network between regions (68 cortical regions). Local connectivity changes, in terms of the number of changed regions and the magnitude of changes, increased with disease duration. Local connectivity yielded a better surgical outcome prediction (Mean value: 95.39% accuracy, 92.76% sensitivity, and 100% specificity) than global connectivity. Connectivity within regions, compared to structural connectivity between brain regions, can be a more efficient biomarker for epilepsy assessment and surgery outcome prediction of medically intractable TLE.