Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the morphokinetic parameters and development of pre‐implantation embryos obtained by testicular, epididymal and ejaculate spermatozoa using time‐lapse imaging system

Low sperm quality has negative effects on fertilisation and embryo development. The males with azoospermia apply for testicular sperm extraction (TESE) or microsurgical epididymal sperm aspiration (MESA) in order to retrieve sperm. To date, there have not been any reports investigating morphokinetic parameters of pre‐implantation embryos using testicular and epididymal spermatozoa. Therefore, we aimed to correlate embryo development and assess morphogenetic parameters in embryos obtained by TESE and MESA using time‐lapse imaging. A total of 60 patients undergoing IVF treatments were included in this study. Twenty men with normal semen parameters were selected as control group. Twenty men undergoing TESE and 20 men undergoing MESA were also included in this study. The morphokinetic parameters of time intervals between the second polar body (PB2) extrusion, pronuclei formation and disappearance and cleavage divisions showed significant variations in TESE, MESA and control groups. Furthermore, the pregnancy rates (positive beta‐hCG) were shown to be similar in both TESE and the control group (55% in each group), whereas for the MESA group, this rate was significantly lower (39%, p = 0.049). Further extrapolation of these results may implicate that the obstructive azoospermia patients should undergo TESE instead of MESA for better blastocyst development and higher pregnancy rates.
Bifacial cambium stem cells generate xylem and phloem during radial plant growth

ABSTRACT A reduced rate of stem cell division is considered a widespread feature which ensures the integrity of genetic information during somatic development of plants and animals. Radial growth of plant shoots and roots is a stem cell-driven process that is fundamental for the mechanical and physiological support of enlarging plant bodies. In most dicotyledonous species, the underlying stem cell niche, the cambium, generates xylem inwards and phloem outwards. Despite the importance and intriguing dynamics of the cambium, the functional characterization of its stem cells is hampered by the lack of experimental tools for accessing distinct cambium sub-domains. Here, we use the hypocotyl of Arabidopsis thaliana to map stem cell activity in the proliferating cambium. Through pulse labeling and genetically encoded lineage tracing, we find that a single bifacial stem cell generates both xylem and phloem cell lineages. This cell is characterized by a specific combination of PXY (TDR), SMXL5 and WOX4 gene activity and a high division rate in comparison with tissue-specific progenitors. Our analysis provides a cellular fate map of radial plant growth, and suggests that stem cell quiescence is not a general prerequisite for life-long tissue production. This article has an associated ‘The people behind the papers’ interview. Highlighted Article: A single bifacial stem cell that is characterized by the combined activity of PXY (TDR), SMXL5 and WOX4 genes generates both wood and bast during radial plant growth.
Therapy for prevention and treatment of skin ionizing radiation damage: a review

Abstract Radiologic accidents or terrorist acts involving radioactive material, as well as radiation exposure in medical or industrial procedures are potential sources of risk for human health. All these risks share a common element, exposure to ionizing radiation. The extent of ionizing radiation injury will depend on a number of independent variables such as dose, type of radiation and tissue, etc. As a result of ionizing radiation exposure, biological effects can take place in acute or long-term manner. As in the case of other self-renewing tissues (e.g. hematopoietic system and intestinal epithelium), skin is also extremely sensitive to ionizing radiation. In this way, appropriate management of radiation skin effects might improve the therapeutic benefit of medical radiation therapy, as well as reduce the mortality associated with any radiological incident (e.g. accident or terrorist attack). For this reason, current and potential future treatment approaches for skin radiation injury are reviewed in this work. Unfortunately, there is no sufficient evidence for establishing a standard treatment to prevent or mitigate radiation-induced cutaneous injury. Thus, continued research is necessary to achieve effective therapies to address this important health problem.
Electrical stimulation of human corticospinal axons at the level of the lumbar spinal segments

Electrical stimulation over the mastoids or thoracic spinous processes has been used to assess subcortical contribution to corticospinal excitability, but responses are difficult to evoke in the resting lower limbs or are limited to only a few muscle groups. This might be mitigated by delivering the stimuli lower on the spinal column, where the descending tracts contain a greater relative density of motoneurons projecting to lower limb muscles. We investigated activation of the corticospinal axons innervating tibialis anterior (TA) and rectus femoris (RF) by applying a single electrical stimulus over the first lumbar spinous process (LS). LS was paired with transcranial magnetic stimulation (TMS) at interstimulus intervals (ISIs) of −16 (TMS before LS) to 14 ms (LS before TMS). The relationship between muscle contraction strength (10%–100% maximal) and the amplitude of single‐pulse TMS and LS responses was also investigated. Compared to the responses to TMS alone, responses to paired stimulation were significantly occluded in both muscles for ISIs ≥−8 ms (p ≤ 0.035), consistent with collision of descending volleys from TMS with antidromic volleys originating from LS. This suggests that TMS and LS activate some of the same corticospinal axons. Additionally, the amplitude of TMS and LS responses increased with increasing contraction strengths with no change in onset latency, suggesting responses to LS are evoked transsynaptically and have a monosynaptic component. Taken together, these experiments provide evidence that LS is an alternative method that could be used to discern segmental changes in the corticospinal tract when targeting lower limb muscles.
Cytotoxic effects of Shiga toxin-2 on human extravillous trophoblast cell lines.

Shiga toxin (Stx2) producing Escherichia coli infections during early gestation may impair placentation through a Stx2 damage of extravillous trophoblast (EVT) cells. We have previously demonstrated that Stx2 injected in rats in the early stage of pregnancy causes spontaneous abortion by a direct cytotoxic effect in the highly perfused feto-uteroplacental unit. The main aim was to evaluate the effects of Stx2 on EVT in order to understand the possible adverse effects that the toxin may cause on trophoblast cells during early pregnancy. Swan 71 and HTR-8 cell lines were used as human EVT models. The presence of Stx2 receptor, globotriaosylceramide (Gb3), on Swan 71 and HTR-8 cells was evaluated by thin layer chromatography. The effects of Stx2 on cell viability were evaluated by neutral red uptake, migration by wound healing assay and invasion was determined by the "transwell chamber" assay. Metalloproteinase activity (MMP-2) was evaluated by zymography and tubulogenesis was analyzed by counting the total tube length and the number of branches formation. We have demonstrated that Swan 71 expresses high levels of Gb3 compared to HTR-8 cells. Stx2 decreased significantly Swan 71 viability in a dose dependent manner after 72 h of toxin exposure. Furthermore, Stx2 impaired migration, invasion and tube-like formation of Swan 71 cells and decreased the MMP-2 activity. These cytotoxic effects were partially prevented by aminoguanidine, an inducible nitric oxide synthase inhibitor. These studies demonstrate that the function and viability of EVT cells may be altered by Stx2 and suggest that NO overexpression may be involved in the detrimental effects.
Vitamins E and C prevent apoptosis of testicular and ovarian tissues following mancozeb exposure in the first-generation mouse pups

The aim of this study was to evaluate the role of apoptosis in the first-generation pups’ testicular and ovarian tissue changes following mancozeb (MNZ) administration during intrauterine and lactating periods and also the preventive effect of the co-administration of vitamins E and C on these changes. Naval Medical Research Institute (NMRI) pregnant mice were randomly divided into six groups: control, vehicle, MNZ, vitamin E plus MNZ, vitamin C plus MNZ and vitamins E and C plus MNZ. Administered doses of MNZ and vitamins E and C were 500, 200 and 100 mg/kg of body weight, respectively. These agents were administered to the animals by oral gavage every 2 days. Vitamin treatment was carried out 30 min prior to MNZ administration. Treatment was started on the second day of gestation and continued until weaning. Separated testes and ovaries of animals were prepared for apoptosis detection by terminal deoxynucleotidyl transferase end-labeling (TUNEL) staining. The percentage of TUNEL-positive cells was reported using the 4,6-diamidino-2-phenylindole method. As compared to the control and vehicle groups, MNZ induced a significant increase (p < 0.001) in the number of TUNEL-positive cells. The administration of both vitamins E and C alone and together significantly (p < 0.001) prevented the apoptotic impacts of MNZ. The preventive effect of the co-administration of these vitamins on the ovary was greater compared to the single administration of vitamins E (p < 0.001) or C (p < 0.001). Meanwhile, the results revealed the stronger preventive effect of vitamin C as compared to E on testicular tissue (p < 0.05). The apoptotic impact of MNZ exposure during intrauterine and lactating periods on first-generation testicular and ovarian tissues was significant. The co-administration of vitamins E and C could prevent MNZ-induced testicular and ovarian changes.
Ciprofloxacin Enhances the Chemosensitivity of Cancer Cells to ABCB1 Substrates

ABCB1 is one of the major drug efflux transporters that is known to cause multidrug resistance (MDR) in cancer patients receiving chemotherapy for the treatment of solid tumors and hematological malignancies. Inhibition of ABCB1 efflux function is important for maintaining the intracellular concentration of chemotherapeutic drugs. Here, we evaluated ciprofloxacin for its ability to reverse MDR caused by the overexpression of ABCB1. Cytotoxicity of ciprofloxacin was determined by the MTT assay. The chemosensitizing effects of ciprofloxacin were determined in combination with ABCB1 substrates. The intracellular accumulation and efflux of ABCB1 substrates was measured by a scintillation counter, and protein expression was determined by the Western blotting. Vanadate-sensitive ATPase assay was performed to determine the effect of ciprofloxacin on the ATPase activity of ABCB1, and docking analysis was done to determine the interaction of ciprofloxacin with ABCB1. Ciprofloxacin significantly potentiated the cytotoxic effects of ABCB1 substrates in ABCB1-overexpressing cells. Furthermore, ciprofloxacin increased the intracellular accumulation and decreased the efflux of [3H]-paclitaxel without altering the expression of ABCB1. Ciprofloxacin stimulated the ATPase activity of ABCB1 in a concentration-dependent manner. Our findings showed that ciprofloxacin potently inhibits the ABCB1 efflux function and it has potential to be developed as a combination anticancer therapy.
Aspergillolide, a new 12-membered macrolide from sea cucumber-derived fungus Aspergillus sp. S-3-75

Abstract A new 12-membered macrolide, aspergillolide (1), along with nine known compounds (2–10), were isolated from the fungus Aspergillus sp. S-3-75 associated with the sea cucumber Holothuria nobilis Selenka. The structure and absolute stereochemistry of 1 were elucidated on the basis of extensive spectroscopic methods and single crystal X-ray diffraction analysis. Graphical Abstract
Smell of Infection: A Novel, Noninvasive Method for Detection of Fish Excretory-Secretory Proteins

Chemical signals are produced by aquatic organisms following predatory attacks or perturbations such as parasitic infection. Ectoparasites feeding on fish hosts are likely to cause release of similar alarm cues into the environment due to the stress, wounding, and immune response stimulated upon infection. Alarm cues are often released in the form of proteins, antimicrobial peptides, and immunoglobulins that provide important insights into bodily function and infection status. Here we outline a noninvasive method to identify potential chemical cues associated with infection in fish by extracting, purifying, and characterizing proteins from water samples from cultured fish. Gel free proteomic methods were deemed the most suitable for protein detection in saline water samples. It was confirmed that teleost proteins can be characterized from water and that variation in protein profiles could be detected between infected and uninfected individuals and fish and parasite only water samples. Our novel assay provides a noninvasive method for assessing the health condition of both wild and farmed aquatic organisms. Similar to environmental DNA monitoring methods, these proteomic techniques could provide an important tool in applied ecology and aquatic biology.
Pocket guide for nonprescription product therapeutics

This timely new resource contains selected content from the popular text "Nonprescription Product Therapeutics", providing all the necessary information for patient counseling situations. Lightweight and portable in a pocket-sized format, it's the ideal resource for pharmacy students and practicing pharmacists alike. There's no other rapid reference like it currently available. Its features include counseling tips that highlight information patients need to know, patient assessment algorithms that guide you through complex therapeutic decisions, alerts on dangerous or life-threatening ingredients, actions, or situations, and a color insert containing 48 photos of disorders to aid in suggesting medications.
Automatic Extraction of Contextual Co-occurrence Chain and Its Relationship with Textual Cohesion

Abstract Semantic lexical chains have been regarded as important in textural cohesion, although traditionally, the classification of these chains has been limited to repetition, synonymy, hyponymy, and collocates. The cases of automatic extraction of lexical chains have found that the contextual synonyms can not be recognized, nor extracted automatically. This study took the data-based technology to extract the contextually co-occurring lexical chains through thematic lexical items. It found that these contextually co-occurring lexical chains can include the semantic lexical chains and contextual synonyms. It also found that, in extraction of collocates of the co-occurring lexical items, these collocates form secondary lexical chains, which contribute to textual cohesion. The vertical lexical chains made of contextually co-occurring lexical items and the horizontal chains made of collocational lexical items work together in making the text into a coherent whole. 语义词汇链被认为是语篇衔接的重要手段，但是传统上对其的分类局限在重复、同义词、上下义词和搭配等方面。 在据此进行的词汇链自动提取的案例中，发现语境同义词没有得到承认，更无法进行自动提取。 在此基础上，本项研究采取以数据为基础的计算技术，提取主题词汇的语境共现词汇链，发现其完全可以涵盖语义词汇链和语境同义词，并且在提取共现词汇的搭配词汇时，发现这些搭配词汇实际上形成二级词汇链参与语篇的衔接。 如此语境共现词汇构成的纵向词汇链和搭配词汇构成的横向词汇链，使得语篇成为连贯的整体。
Community-Driven Health Priorities for Healthy Aging With HIV

Abstract Palm Springs, CA, is a retirement community with the highest prevalence of gay men living with HIV older than 50 years in the United States. Through a community–academic partnership, we explored the major health issues, resiliencies, and priority research topics related to HIV and aging. We conducted five community facilitated focus groups with different stakeholders, including two focus groups with older adults living with HIV, one with their caregivers, one with HIV-focused community-based organizations, and a joint focus group with researchers and HIV care providers. Using the rigorous and accelerated data reduction technique, five major themes emerged, which included long-term side effects of medication, social determinants of health, mental health, resiliencies, and involving community in research. These data are important for developing effective interventions, conducting useful and impactful research, and providing health care providers with the tools and knowledge to provide optimal care.
A suite of complementary biocontrol traits allows a native consortium of root‐associated bacteria to protect their host plant from a fungal sudden‐wilt disease

The beneficial effects of plant‐–bacterial interactions in controlling plant pests have been extensively studied with single bacterial isolates. However, in nature, bacteria interact with plants in multitaxa consortia, systems which remain poorly understood. Previously, we demonstrated that a consortium of five native bacterial isolates protected their host plant Nicotiana attenuata from a sudden wilt disease. Here we explore the mechanisms behind the protection effect against the native pathosystem. Three members of the consortium, Pseudomonas azotoformans A70, P. frederiksbergensis A176 and Arthrobacter nitroguajacolicus E46, form biofilms when grown individually in vitro, and the amount of biofilm increased synergistically in the five‐membered consortium, including two Bacillus species, B. megaterium and B. mojavensis. Fluorescence in situ hybridization and scanning electron microscopy in planta imaging techniques confirmed biofilm formation and revealed locally distinct distributions of the five bacterial strains colonizing different areas on the plant‐root surface. One of the five isolates, K1 B. mojavensis produces the antifungal compound surfactin, under in vitro and in vivo conditions, clearly inhibiting fungal growth. Furthermore, isolates A70 and A176 produce siderophores under in vitro conditions. Based on these results we infer that the consortium of five bacterial isolates protects its host against fungal phytopathogens via complementary traits. The study should encourage researchers to create synthetic communities from native strains of different genera to improve bioprotection against wilting diseases.
Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk: Insights From the FOURIER Trial

Background: Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction remains undefined. Methods: Lp(a) was measured in 25 096 patients in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a randomized trial of evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease (median follow-up, 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration. Results: The median (interquartile range) baseline Lp(a) concentration was 37 (13–165) nmol/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease death, myocardial infarction, or urgent revascularization (adjusted hazard ratio quartile 4: quartile 1, 1.22; 95% CI, 1.01–1.48) independent of low-density lipoprotein cholesterol. At 48 weeks, evolocumab significantly reduced Lp(a) by a median (interquartile range) of 26.9% (6.2%–46.7%). The percent change in Lp(a) and low-density lipoprotein cholesterol at 48 weeks in patients taking evolocumab was moderately positively correlated (r=0.37; 95% CI, 0.36–0.39; P<0.001). Evolocumab reduced the risk of coronary heart disease death, myocardial infarction, or urgent revascularization by 23% (hazard ratio, 0.77; 95% CI, 0.67–0.88) in patients with a baseline Lp(a) >median, and by 7% (hazard ratio, 0.93; 95% CI, 0.80–1.08; P interaction=0.07) in those ⩽median. Coupled with the higher baseline risk, the absolute risk reductions, and number needed to treat over 3 years were 2.49% and 40 versus 0.95% and 105, respectively. Conclusions: Higher levels of Lp(a) are associated with an increased risk of cardiovascular events in patients with established cardiovascular disease irrespective of low-density lipoprotein cholesterol. Evolocumab significantly reduced Lp(a) levels, and patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) and tended to derive greater coronary benefit from PCSK9 inhibition. Clinical Trial Registration: URL: https://www.clinicaltrials. gov. Unique identifier: NCT01764633.
Inhibition of radiographic progression in psoriatic arthritis by adalimumab independent of the control of clinical disease activity

Abstract Objectives To evaluate the relationship between radiographic progression and disease activity in subjects with PsA treated with adalimumab (ADA) or placebo (PBO) and the impact of concomitant MTX. Methods This was a post hoc analysis of the randomized, double-blind, PBO-controlled ADEPT trial. Subjects were categorized according to time-averaged (TA) disease activity (remission, low, moderate or high) based on Disease Activity Score of 28 joints with CRP [DAS28(CRP)], Disease Activity Index for Psoriatic Arthritis (DAPSA) or Psoriatic Arthritis Disease Activity Score (PASDAS), and achievement of minimal disease activity (MDA) at week 24. Radiographic progression was assessed as change in modified total Sharp score (ΔmTSS) from baseline to week 24. The analyses included interaction terms between disease activity and treatment on radiographic progression, comparison of radiographic progression in subjects categorized by disease activity and treatment, and correlation between disease activity and radiographic progression by treatment. Results The interaction terms for TA disease activity and treatment on ΔmTSS were significant (P = 0.002–0.008). Irrespective of concomitant MTX, ΔmTSS was lower with ADA vs PBO in all disease activity categories. Importantly, even in subjects having moderate or high disease activity or not achieving MDA, ΔmTSS was significantly lower on ADA than PBO (P = 0.05–0.001 for TA-DAPSA, TA-PASDAS and MDA). Correlations between TA disease activity scores and ΔmTSS were moderately positive and significant (P < 0.001) with PBO but non-significant with ADA. Conclusion Among subjects with PsA treated with ADA, there was evidence of a ‘disconnect’ between disease activity and radiographic progression: inhibition of radiographic progression was greater than expected based on control of clinical disease activity alone. MTX had no added effect. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT00646386.