Miracle-dz/UniFAR-FTUs huggingface dataset:
Is There a Brain Microbiome?

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome. ”
Wound Healing Activity of 80% Methanol Leaf Extract of Zehneria scabra (L.f) Sond (Cucurbitaceae) in Mice

Background Zehneria scabra is one of the folklore plants of Ethiopia frequently used for external wound treatment in humans. Nevertheless, pharmacological investigations have not been performed to substantiate activity of the plant extract in wound healing. Hence, this study attempted to explore the activity of leaf extract of Z. scabra in wound healing using a mice model. Materials and Methods The air-dried leaf from Z. scabra was pulverized and extracted with 80% methanol and prepared with 5% and 10% extract ointments. An acute dermal toxicity study of the extract was conducted in female mice by observing the signs of toxicity. Then 5% and 10% (w/w) ointments of the extract were applied topically to investigate their wound healing activity in incision and excision wound models. Parameters such as wound contraction, period of epithelialization, and tensile strength were determined. Results Upon the application of 10% w/w extract ointment, no signs of dermal toxicity were observed in mice. Both 5% and 10% (w/w) extract ointment formulations increased percentage wound contraction and tensile strength, and shortened the epithelialization period. Conclusion The findings of this study collectively showed that the leaf extract of Z. scabra possessed significant wound healing activity, upholding the folkloric use of the experimental plant.
Percutaneous Osteoplasty for the Management of a Talar Metastasis: A Case Report

Background Talar metastasis is very rare among all bone metastases. Routine radiotherapy and chemotherapy are the main treatment measures at present. Nevertheless, some patients still experience unbearable cancer pain that cannot be effectively relieved with powerful painkillers. Case Report We report a patient with advanced renal carcinoma suffering from unbearable pain due to multiple bone metastases that involved several vertebrae (T11, L1, and L2) and the left talus. After percutaneous vertebroplasty in the vertebrae, the pain in the left talus became more prominent. We performed a percutaneous osteoplasty to manage the talar metastasis. Postoperatively, the pain level remarkably decreased, and the patient’s activity capacity significantly improved. Conclusion Percutaneous osteoplasty is an alternative method for talar metastasis that can alleviate pain immediately and improve the quality of life in patients with advanced malignant tumors.
Women with Hemophilia: Case Series of Reproductive Choices and Review of Literature

Abstract Aim Very little is known regarding reproductive choices, pregnancy, and delivery of women with moderate to severe hemophilia. Our aim was to describe our experience with three hemophiliac women and their journey to achieve motherhood. Methods Medical charts of women with moderate to severe hemophilia A treated at our center were evaluated. Data regarding choices of conception, pregnancy course, mode of delivery, and pregnancy outcomes were obtained. Results Three women are presented. Whereas patient 1 chose to adopt her first child and later had twins through egg donations and a surrogate mother, patient 2 underwent spontaneous pregnancy and delivered via cesarean section. Patient 3 preferred in vitro fertilization and preimplantation genetic diagnosis to avoid hemophilia and hemophilia carriership in her offspring. Conclusion The appropriate means to achieve parenthood for women with moderate to severe hemophilia should be individualized and requires support of a comprehensive multidisciplinary team.
Mind the replication gap

Unlike bacteria, mammalian cells need to complete DNA replication before segregating their chromosomes for the maintenance of genome integrity. Thus, cells have evolved efficient pathways to restore stalled and/or collapsed replication forks during S-phase, and when necessary, also to delay cell cycle progression to ensure replication completion. However, strong evidence shows that cells can proceed to mitosis with incompletely replicated DNA when under mild replication stress (RS) conditions. Consequently, the incompletely replicated genomic gaps form, predominantly at common fragile site regions, where the converging fork-like DNA structures accumulate. These branched structures pose a severe threat to the faithful disjunction of chromosomes as they physically interlink the partially duplicated sister chromatids. In this review, we provide an overview discussing how cells respond and deal with the under-replicated DNA structures that escape from the S/G2 surveillance system. We also focus on recent research of a mitotic break-induced replication pathway (also known as mitotic DNA repair synthesis), which has been proposed to operate during prophase in an attempt to finish DNA synthesis at the under-replicated genomic regions. Finally, we discuss recent data on how mild RS may cause chromosome instability and mutations that accelerate cancer genome evolution.
Stability of trusses by graphic statics

This paper presents a graphical method for determining the linearized stiffness and stability of prestressed trusses consisting of rigid bars connected at pinned joints and which possess kinematic freedoms. Key to the construction are the rectangular areas which combine the reciprocal form and force diagrams in the unified Maxwell–Minkowski diagram. The area of each such rectangle is the product of the bar tension and the bar length, and this corresponds to the rotational stiffness of the bar that arises due to the axial force that it carries. The prestress stability of any kinematic freedom may then be assessed using a weighted sum of these areas. The method is generalized to describe the out-of-plane stability of two-dimensional trusses, and to describe three-dimensional trusses in general. The paper also gives a graphical representation of the ‘product forces’ that were introduced by Pellegrino and Calladine to describe the prestress stability of trusses.
Perception of infection: disease-related social cues influence immunity in songbirds

While avoidance of sick conspecifics is common among animals, little is known about how detecting diseased conspecifics influences an organism's physiological state, despite its implications for disease transmission dynamics. The avian pathogen Mycoplasma gallisepticum (MG) causes obvious visual signs of infection in domestic canaries (Serinus canaria domestica), including lethargy and conjunctivitis, making this system a useful tool for investigating how the perception of cues from sick individuals shapes immunity in healthy individuals. We tested whether disease-related social information can stimulate immune responses in canaries housed in visual contact with either healthy or MG-infected conspecifics. We found higher complement activity and higher heterophil counts in healthy birds viewing MG-infected individuals around 6–12 days post-inoculation, which corresponded with the greatest degree of disease pathology in infected stimulus birds. However, we did not detect the effects of disease-related social cues on the expression of two proinflammatory cytokines in the blood. These data indicate that social cues of infection can alter immune responses in healthy individuals and suggest that public information about the disease can shape how individuals respond to infection.
Probabilistic quantification of tsunami current hazard using statistical emulation

In this paper, statistical emulation is shown to be an essential tool for the end-to-end physical and numerical modelling of local tsunami impact, i.e. from the earthquake source to tsunami velocities and heights. In order to surmount the prohibitive computational cost of running a large number of simulations, the emulator, constructed using 300 training simulations from a validated tsunami code, yields 1 million predictions. This constitutes a record for any realistic tsunami code to date, and is a leap in tsunami science since high risk but low probability hazard thresholds can be quantified. For illustrating the efficacy of emulation, we map probabilistic representations of maximum tsunami velocities and heights at around 200 locations about Karachi port. The 1 million predictions comprehensively sweep through a range of possible future tsunamis originating from the Makran Subduction Zone (MSZ). We rigorously model each step in the tsunami life cycle: first use of the three-dimensional subduction geometry Slab2 in MSZ, most refined fault segmentation in MSZ, first sediment enhancements of seabed deformation (up to 60% locally) and bespoke unstructured meshing algorithm. Owing to the synthesis of emulation and meticulous numerical modelling, we also discover substantial local variations of currents and heights.
‘All Things to All People’: 1 Corinthians, Ethnic Flexibility, and Social Identity Theory

Since Judge’s pioneering 1960 monograph on social engagement in early Christian groups there have been a host of further sociological and social-psychological engagements with ancient texts. One relative newcomer to the biblical research discipline is the socio-cognitive engagement of Social Identity Theory (SIT) and its attendant approaches. This article traces how Social Identity Theory has been applied to the biblical texts, using 1 Corinthians as an exemplary case. We trace the development of social approaches to 1 Corinthians from Theissen’s early engagements through to the current applications of SIT to the text. This is followed by a broad overview of the theory and approaches, along with a brief survey of its application to biblical research, and then 1 Corinthians. Finally, we utilize 1 Cor. 9.19-23 for a brief demonstration of the analytical utility of SIT within the social context of the epistle.
Effect of Nesting Substrate on the Breeding Performance of Peregrine Falcons in Guerrero Negro, Baja California Sur, Mexico, 2012–2016

Abstract. The Peregrine Falcon (Falco peregrinus) breeds locally in the Guerrero Negro wetland complex, Baja California Sur, Mexico, but the most recent investigation of their breeding ecology in this wetland area was in 1998. Our objectives were to update the information on the reproduction of Peregrine Falcons in Guerrero Negro and to evaluate the relationship of reproductive parameters with the environmental temperature, rainfall, and nest substrate (natural or artificial). From 2012 to 2016 we surveyed for Peregrine Falcon nests, and monitored them from February to May each year. We recorded the type of nest substrate (natural or artificial) and the nest contents (eggs, nestlings, or fledglings) at every visit. Pooled across years, we recorded 34 reproductive events that produced 42 fledglings. On average per year, there were 6.8 ± 1.6 egg-laying pairs, and 4.4 ± 1.8 were successful, with a productivity of 1.23 ± 0.06 fledglings/egg-laying pair. Monthly mean air temperatures and rainfall had no effect on breeding parameters; however, there were significant relationships with type of nest substrates. On average, we found falcons had greater nesting success and productivity on artificial substrates (83 ± 15% and 1.91 ± 0.12 fledglings/egg-laying pair) than on natural substrates (36 ± 21% and 0.36 ± 0.21 fledglings/egg-laying pair). Compared to the 1998 estimate, the number of egg-laying pairs in Guerrero Negro has more than doubled (from four to nine); this wetland area currently holds the largest number of breeding pairs along the Baja California Peninsula.
Effect of Supply Chain Collaboration and Service Stakeholder Commitment on Dry Port Firm Performance

A dry port (or land port) is an inland area or intermodal port directly connected to a seaport. Cikarang Dry Port, as one of the best performing dry ports among other dry ports in Indonesia, has only contributed 18% to the loading and unloading volume at Tanjung Priok Port. This study aims to examine the impact of supply chain collaboration and Service Stakeholder Commitment on the performance of dry port companies. The data was collected through a questionnaire that included 55 responses from Cikarang Dry port and maritime logistics companies in Jakarta. The hypotheses were tested by multiple regression. The results of this study confirm that Collaboration in the Supply Chain and the Commitment of Stakeholders in the Service have a positive impact on the performance of port companies. This study provides inspiration for managers to recognize the positive results of supply chain collaboration between service stakeholder engagement organizations to improve port performance in the port supply chain.
Transfer Learning for Classification of Fruit Ripeness Using VGG16

Early diagnosis of maturity carried out by experts in laboratory tests is often not applicable for fast and inexpensive implementation. Using deep learning, an image of various fruits used as data input. Training deep learning models requires large, hard-to-come datasets to perform the task in order to achieve optimal results. In this study. There are 4 research objects, namely apples, oranges, mangoes, and tomatoes used totaling around 9000 training data. Data were trained using 200 epoch iterations using the transfer learning method with the VGG16 models. At the top layer of both models, the same MLP is applied with several parameters, data is converted from RGB to L * a * b with the aim of being a color descriptor on the fruit. Trained using CNN VGG16 with the transfer learning method. The Dropout 0.5 shows the best performance of experiment with 4 scenario that used different technique and show result the best performance with an average score of accuracy rate from scenario 4 is 92%.
Sequencing of myeloma therapy: Finding the right path among many standards

In the last decade, major changes have occurred in the diagnostic criteria, staging system, and response criteria for multiple myeloma (MM). These changes have been accompanied by several advances in treatment of the MM, including many new drugs (carfilzomib, pomalidomide, daratumumab, elotuzumab, panobinostat, ixazomib, selinexor, isatuximab, and belantamab). Numerous clinical trials provide data on best practices along the spectrum of the disease. The purpose of this article is to describe the complexity of MM therapy in a landscape where many parallel standards exist for the same indications, and to provide an outline selecting the first line and subsequent sequencing of therapy according to dynamic changes in the disease and patient features.
Heterogeneous mutation rates and spectra within and between species of yeast and their hybrids

Département de Biologie, Université Laval, Québec, G1V 0A6 Québec, Canada; Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, G1V 0A6 Québec, Canada; Département de Biochimie, Microbiologie et Bioinformatique, Université Laval, Québec, G1V 0A6 Québec, Canada; PROTEO, Le réseau québécois de recherche sur la fonction, la structure et l’ingénierie des protéines, Université Laval, Québec, G1V 0A6 Québec, Canada; Centre de Recherche en Données Massives (CRDM), Université Laval, Québec, G1V 0A6 Québec, Canada; Current address: Département de Biologie Chimie et Géographie, Université du Québec à Rimouski, Rimouski, G5L 3A1, Québec, Canada; Current address: Laurentian Forestry Center, Québec, G1V 4C7 Québec, Canada
Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia

Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disease caused by a splicing mutation in the gene encoding Elongator complex protein 1 (ELP1, also known as IKBKAP). This mutation results in tissue-specific skipping of exon 20 with a corresponding reduction of ELP1 protein, predominantly in the central and peripheral nervous system. Although FD patients have a complex neurological phenotype caused by continuous depletion of sensory and autonomic neurons, progressive visual decline leading to blindness is one of the most problematic aspect of the disease, as it severely affects their quality of life. To better understand the disease mechanism as well as to test the in vivo efficacy of targeted therapies for FD, we have recently generated a novel phenotypic mouse model, TgFD9; Elp1∆20/flox. This mouse exhibits most of the clinical features of the disease and accurately recapitulates the tissue-specific splicing defect observed in FD patients. Driven by the dire need to develop therapies targeting retinal degeneration in FD, herein, we comprehensively characterized the progression of the retinal phenotype in this mouse, and we demonstrated that it is possible to correct ELP1 splicing defect in the retina using the splicing modulator compound (SMC) BPN-15477.
Cryo-EM structure of native human thyroglobulin

The thyroglobulin (TG) protein is essential to thyroid hormone synthesis, plays a vital role in the regulation of metabolism, development and growth and serves as intraglandular iodine storage. Its architecture is conserved among vertebrates. Synthesis of triiodothyronine (T 3 ) and thyroxine (T 4 ) hormones depends on the conformation, iodination and post-translational modification of TG. Although structural information is available on recombinant and deglycosylated endogenous human thyroglobulin (hTG) from patients with goiters, the structure of native, fully glycosylated hTG remained unknown. Here, we present the cryo-electron microscopy structure of native and fully glycosylated hTG from healthy thyroid glands to 3.2 Å resolution. The structure provides detailed information on hormonogenic and glycosylation sites. We employ liquid chromatography–mass spectrometry (LC-MS) to validate these findings as well as other post-translational modifications and proteolytic cleavage sites. Our results offer insights into thyroid hormonogenesis of native hTG and provide a fundamental understanding of clinically relevant mutations. The iodinated thyroglobulin functions as iodine storage and carrier protein and a precursor for thyroid hormone (TH) biogenesis. Here, the authors report the structure of native, fully glycosylated human thyroglobulin, revealing the location of the hTg hormonogenic and glycosylation sites.
Plasmodium falciparum Calcium-Dependent Protein Kinase 4 is Critical for Male Gametogenesis and Transmission to the Mosquito Vector

Transmission of the malaria parasite to the mosquito vector is critical for the completion of the sexual stage of the parasite life cycle and is dependent on the release of male gametes from the gametocyte body inside the mosquito midgut. In the present study, we demonstrate that PfCDPK4 is critical for male gametogenesis and is involved in phosphorylation of proteins essential for male gamete emergence. ABSTRACT Gametocytes of the malaria parasite Plasmodium are taken up by the mosquito vector with an infectious blood meal, representing a critical stage for parasite transmission. Calcium-independent protein kinases (CDPKs) play key roles in calcium-mediated signaling across the complex life cycle of the parasite. We sought to understand their role in human parasite transmission from the host to the mosquito vector and thus investigated the role of the human-infective parasite Plasmodium falciparum CDPK4 in the parasite life cycle. P. falciparum cdpk4− parasites created by targeted gene deletion showed no effect in blood stage development or gametocyte development. However, cdpk4− parasites showed a severe defect in male gametogenesis and the emergence of flagellated male gametes. To understand the molecular underpinnings of this defect, we performed mass spectrometry-based phosphoproteomic analyses of wild-type and Plasmodium falciparum cdpk4− late gametocyte stages to identify key CDPK4-mediated phosphorylation events that may be important for the regulation of male gametogenesis. We further employed in vitro assays to identify these putative substrates of Plasmodium falciparum CDPK4. This indicated that CDPK4 regulates male gametogenesis by directly or indirectly controlling key essential events, such as DNA replication, mRNA translation, and cell motility. Taken together, our work demonstrates that PfCDPK4 is a central kinase that regulates exflagellation and thereby is critical for parasite transmission to the mosquito vector. IMPORTANCE Transmission of the malaria parasite to the mosquito vector is critical for the completion of the sexual stage of the parasite life cycle and is dependent on the release of male gametes from the gametocyte body inside the mosquito midgut. In the present study, we demonstrate that PfCDPK4 is critical for male gametogenesis and is involved in phosphorylation of proteins essential for male gamete emergence. Targeting PfCDPK4 and its substrates may provide insights into achieving effective malaria transmission-blocking strategies.
Anti-allergic and anti-inflammatory activities of black cumin extracts in in vitro and in vivo model systems

Black cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including anti-allergic, bronchial asthma, and anti-inflammatory properties. We sought to evaluate BC extracts’ efficacy for their anti-allergic and anti-inflammatory properties using a comprehensive in vitro, in vivo, and silico experimental setup. To investigate whether BC extract has anti-inflammatory, anti-allergic, and analgesic therapeutic potentials in vitro and in vivo. The activity of BC was assessed through anti-allergic activity on rat basophilic leukemia-2H3 cell line, anti-inflammatory activity on J774.1A cell line, anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test, and ingenuity analysis of the BC extracts in inflammation control. BC exerted potent anti-allergic activity by inhibiting antigen-induced degranulation. An anti-inflammatory effect is shown by inhibiting TNF-α production. The acetic acid-induced writhing test shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test shown the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation. This study suggests that bioactive compounds in BC extract act as an anti-allergic and anti-inflammatory agent by regulating several downstream and upstream inflammation pathways.