Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of the Relationship between Postpartum Health and Mid-Lactation Performance, Behavior, and Feed Efficiency in Holstein Dairy Cows

Simple Summary The transition to lactation is a physiologically challenging period in which dairy cows are more susceptible to postpartum health disorders. Postpartum health disorders are associated with negative outcomes related to milk production, reproduction, and profitability. Feed efficiency is another measure of performance, but its relationship with postpartum health disorders has not been explored. Cows with health disorders have differences in behavior that can be used to help identify them as being ill, but it is unknown how long the behavior remains different. The purpose of the present study was to determine the relationship between postpartum health disorders and mid-lactation performance, feed efficiency, and behaviors. Cows with health disorders had no difference in feed efficiency compared to healthy animals but had differences in behavior during the mid-lactation period. This work indicates that health disorders do not have long-lasting impacts on feed efficiency but may have long-lasting impacts on behavior. Abstract The objective of this study was to investigate the relationships between postpartum health disorders and mid-lactation performance, feed efficiency, and sensor-derived behavioral traits. Multiparous cows (n = 179) were monitored for health disorders for 21 days postpartum and enrolled in a 45-day trial between 50 to 200 days in milk, wherein feed intake, milk yield and components, body weight, body condition score, and activity, lying, and feeding behaviors were recorded. Feed efficiency was measured as residual feed intake and the ratio of fat- or energy-corrected milk to dry matter intake. Cows were classified as either having hyperketonemia (HYK; n = 72) or not (n = 107) and grouped by frequency of postpartum health disorders: none (HLT; n = 94), one (DIS; n = 63), or ≥2 (DIS+; n = 22). Cows that were diagnosed with HYK had higher mid-lactation yields of fat- and energy-corrected milk. No differences in feed efficiency were detected between HYK or health status groups. Highly active mid-lactation time was higher in healthy animals, and rumination time was lower in ≥4th lactation cows compared with HYK or DIS and DIS+ cows. Differences in mid-lactation behaviors between HYK and health status groups may reflect the long-term impacts of health disorders. The lack of a relationship between postpartum health and mid-lactation feed efficiency indicates that health disorders do not have long-lasting impacts on feed efficiency.
CXCR2 Levels Correlate with Immune Infiltration and a Better Prognosis of Triple-Negative Breast Cancers

Simple Summary Tumor microenvironment is critical for cancer progression. The role of the chemokine receptors in breast cancers is still under investigation. The aim of this study was to focus on a retrospective cohort of triple-negative breast cancers (TNBCs) and analyze the involvement of CXCR2 and its link with immune infiltration and immune checkpoint markers. High densities of CXCR2-positive cells were associated with high-grade tumors. Higher quantities of CXCR2-positive cells were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis. Abstract Chemokines and their receptors are key players in breast cancer progression and outcome. Previous studies have shown that the chemokine receptor CXCR2 was expressed at higher levels by cells of the tumor microenvironment in triple-negative breast cancers (TNBCs). The aim of this study was to focus our attention on a retrospective cohort of 290 TNBC cases and analyze the involvement of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) and their link with immune infiltration and immune checkpoint markers. We report that high densities of CXCR2-, CD11b- and CD66b-positive cells were associated with high-grade tumors. Moreover, molecular apocrine TNBCs, defined here as tumors that express both AR and FOXA1 biomarkers, exhibited low levels of CXCR2 and CD11b. High CXCR2 and CD11b levels were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. On the other hand, CD66b levels were associated only with CD8+, stromal PD-L1 and PD-1 expression. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Finally, in TNBC treated with adjuvant chemotherapy, CXCR2 density was associated with longer RFS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis.
Structural Identification between Phthalazine-1,4-Diones and N-Aminophthalimides via Vilsmeier Reaction: Nitrogen Cyclization and Tautomerization Study

N-Aminophthalimides and phthalazine 1,4-diones were synthesized from isobenzofuran-1,3-dione, isoindoline-1,3-dione, furo [3,4-b] pyrazine-5,7-dione, or 1H-pyrrolo [3,4-c] pyridine-1,3-dione with monohydrate hydrazine to carry out the 5-exo or 6-endo nitrogen cyclization under the different reaction conditions. Based on the control experimental results, 6-endo thermodynamic hydrohydrazination and kinetical 5-exo cyclization reactions were individually selective formation. Subsequently, Vilsmeier amidination derivatization was successfully developed to probe the structural divergence between N-aminophthalimide 2 and phthalazine 1,4-dione 3. On the other hand, the best tautomerization of N-aminophthalimide to diazinone was also determined under acetic acid mediated solution.
Full-Endoscopic Lumbar Decompression versus Open Decompression and Fusion Surgery for the Lumbar Spinal Stenosis: A 3-Year Follow-Up Study

Purpose Compare the efficacy of full-endoscopic lumbar decompression surgery (FELDS) and open decompression and fusion surgery (ODFS) for lumbar spinal stenosis (LSS). Patients and Methods A retrospective analysis of 358 LSS patients treated by FELDS (“FELD” group) or ODFS (“open” group) was undertaken. There were 177 patients in the FELDS group with a mean age of 65.47±9.26 years and 181 patients in the open group with a mean age of 64.18±10.24 years. Duration of follow-up was 38.63±11.88 months in the FELDS group and 38.56±12.29 months in the open group. Visual analog scale (VAS) score, Oswestry Disability Index (ODI), and Modified MacNab criteria were used to access clinical outcomes. Surgical outcomes (duration of surgical procedure, blood loss, complications, duration of postoperative hospital stay (DOPHS), prevalence of revision procedures) were evaluated. Magnetic resonance imaging was used to evaluate the change in the Pfirrmann grade at adjacent segments. Results VAS score (leg and back) and ODI improved significantly in both groups (P<0.001). Success rate reached 86.55% and 90.60% in the FELDS group and open group (P>0.05), respectively. Procedure duration (84.12 vs 112.08 min), blood loss (7.97 vs 279.67 mL), and DOPHS (2.68 vs 4.78 days) of the FELDS group were significantly better than those of the open group (P<0.05). Total prevalence of complications and procedure revisions was 14.69% and 10.73% in the FELD group, respectively, but did not show a significant difference with that in the open group (12.15% and 9.39%, respectively). The Pfirrmann grade increased in 13.04% of adjacent segments in the FELDS group, significantly better than that in the open group (32.67%) (P<0.05). Conclusion FELDS had the same efficacy as ODFS for LSS treatment. FELDS had the advantages of minimal invasiveness, less surgical trauma, rapid recovery, and lower risk of degeneration of adjacent segments compared with that of ODFS.
Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract’s antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein–protein and protein–compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.
68Ga-Labeling: Laying the Foundation for an Anti-Radiolytic Formulation for NOTA-sdAb PET Tracers

During the preparation of [68Ga]Ga-NOTA-sdAb at high activity, degradation of the tracers was observed, impacting the radiochemical purity (RCP). Increasing starting activities in radiolabelings is often paired with increased degradation of the tracer due to the formation of free radical species, a process known as radiolysis. Radical scavengers and antioxidants can act as radioprotectant due to their fast interaction with formed radicals and can therefore reduce the degree of radiolysis. This study aims to optimize a formulation to prevent radiolysis during the labeling of NOTA derivatized single domain antibody (sdAbs) with 68Ga. Gentisic acid, ascorbic acid, ethanol and polyvinylpyrrolidone were tested individually or in combination to find an optimal mix able to prevent radiolysis without adversely influencing the radiochemical purity (RCP) or the functionality of the tracer. RCP and degree of radiolysis were assessed via thin layer chromatography and size exclusion chromatography for up to three hours after radiolabeling. Individually, the radioprotectants showed insufficient efficacy in reducing radiolysis when using high activities of 68Ga, while being limited in amount due to negative impact on radiolabeling of the tracer. A combination of 20% ethanol (VEtOH/VBuffer%) and 5 mg ascorbic acid proved successful in preventing radiolysis during labeling with starting activities up to 1–1.2 GBq of 68Ga, and is able to keep the tracer stable for up to at least 3 h after labeling at room temperature. The prevention of radiolysis by the combination of ethanol and ascorbic acid potentially allows radiolabeling compatibility of NOTA-sdAbs with all currently available 68Ge/68Ga generators. Additionally, a design is proposed to allow the incorporation of the radioprotectant in an ongoing diagnostic kit development for 68Ga labeling of NOTA-sdAbs.
PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central to the important functions of PARP enzymes in the DNA damage response and nucleosome remodelling. Activation of PARP happens through DNA binding via zinc fingers and/or the WGR domain. Modulation of their activity using PARP inhibitors occupying the NAD+ binding site has proven successful in cancer therapies. For decades, studies set out to elucidate their full-length molecular structure and activation mechanism. In the last five years, significant advances have progressed the structural and functional understanding of PARP1-3, such as understanding allosteric activation via inter-domain contacts, how PARP senses damaged DNA in the crowded nucleus, and the complementary role of histone PARylation factor 1 in modulating the active site of PARP. Here, we review these advances together with the versatility of PARP domains involved in DNA binding, the targets and shape of PARylation and the role of PARPs in nucleosome remodelling.
Development of Immunochromatographic Test Kit for Rapid Detection of Specific IgG4 Antibody in Whole-Blood Samples for Diagnosis of Human Gnathostomiasis

Human gnathostomiasis is a harmful food-borne zoonosis caused by roundworms of the genus Gnathostoma. The parasite can occasionally migrate to the central nervous system, causing life-threatening disease and death. Here, we report a new point-of-care (POC) test kit, the gnathostomiasis blood immunochromatographic test (GB-ICT) kit. The kit is based on recombinant Gnathostoma spinigerum antigen and detects specific IgG4 antibody in whole-blood samples (WBSs). The GB-ICT kit showed potentially high diagnostic values with simulated WBSs (n = 248), which were obtained by spiking patients’ sera with red blood cells. The accuracy, sensitivity, specificity, and positive and negative predictive values were 95.2%, 100%, 93.8%, 81.5%, and 100%, respectively. Ten WBSs from clinically suspected gnathostomiasis patients were all positive according to the GB-ICT kit, while 10 WBSs from healthy volunteers were negative. The GB-ICT kit is a simple and convenient POC testing tool using finger-prick blood samples: venous blood sampling and serum separation processes are not required. The GB-ICT kit can support clinical diagnosis in remote areas and field settings without sophisticated equipment facilities.
Design and Validation of a Process Based on Cationic Niosomes for Gene Delivery into Novel Urine-Derived Mesenchymal Stem Cells

Background: Mesenchymal stem cells (MSCs) are stem cells present in adult tissues. They can be cultured, have great growth capacity, and can differentiate into several cell types. The isolation of urine-derived mesenchymal stem cells (hUSCs) was recently described. hUSCs present additional benefits in the fact that they can be easily obtained noninvasively. Regarding gene delivery, nonviral vectors based on cationic niosomes have been used and are more stable and have lower immunogenicity than viral vectors. However, their transfection efficiency is low and in need of improvement. Methods: We isolated hUSCs from urine, and the cell culture was tested and characterized. Different cationic niosomes were elaborated using reverse-phase evaporation, and they were physicochemically characterized. Then, they were screened into hUSCs for transfection efficiency, and their internalization was evaluated. Results: GPxT-CQ at a lipid/DNA ratio of 5:1 (w/w) had the best transfection efficiency. Intracellular localization studies confirmed that nioplexes entered mainly via caveolae-mediated endocytosis. Conclusions: In conclusion, we established a protocol for hUSC isolation and their transfection with cationic niosomes, which could have relevant clinical applications such as in gene therapy. This methodology could also be used for creating cellular models for studying and validating pathogenic genetic variants, and even for performing functional studies. Our study increases knowledge about the internalization of tested cationic niosomes in these previously unexplored cells.
Sensory-Motor Mechanisms Increasing Falls Risk in Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is associated with peripheral sensory and motor nerve damage that affects up to half of diabetes patients and is an independent risk factor for falls. Clinical implications of DPN-related falls include injury, psychological distress and physical activity curtailment. This review describes how the sensory and motor deficits associated with DPN underpin biomechanical alterations to the pattern of walking (gait), which contribute to balance impairments underpinning falls. Changes to gait with diabetes occur even before the onset of measurable DPN, but changes become much more marked with DPN. Gait impairments with diabetes and DPN include alterations to walking speed, step length, step width and joint ranges of motion. These alterations also impact the rotational forces around joints known as joint moments, which are reduced as part of a natural strategy to lower the muscular demands of gait to compensate for lower strength capacities due to diabetes and DPN. Muscle weakness and atrophy are most striking in patients with DPN, but also present in non-neuropathic diabetes patients, affecting not only distal muscles of the foot and ankle, but also proximal thigh muscles. Insensate feet with DPN cause a delayed neuromuscular response immediately following foot–ground contact during gait and this is a major factor contributing to increased falls risk. Pronounced balance impairments measured in the gait laboratory are only seen in DPN patients and not non-neuropathic diabetes patients. Self-perception of unsteadiness matches gait laboratory measures and can distinguish between patients with and without DPN. Diabetic foot ulcers and their associated risk factors including insensate feet with DPN and offloading devices further increase falls risk. Falls prevention strategies based on sensory and motor mechanisms should target those most at risk of falls with DPN, with further research needed to optimise interventions.
Crosstalk between Interleukin-1β and Type I Interferons Signaling in Autoinflammatory Diseases

Interleukin-1β (IL-1β) and type I interferons (IFNs) are major cytokines involved in autoinflammatory/autoimmune diseases. Separately, the overproduction of each of these cytokines is well described and constitutes the hallmark of inflammasomopathies and interferonopathies, respectively. While their interaction and the crosstalk between their downstream signaling pathways has been mostly investigated in the frame of infectious diseases, little information on their interconnection is still available in the context of autoinflammation promoted by sterile triggers. In this review, we will examine the respective roles of IL-1β and type I IFNs in autoinflammatory/rheumatic diseases and analyze their potential connections in the pathophysiology of some of these diseases, which could reveal novel therapeutic opportunities.
The Inclusion of Rights of People with Disabilities and Women and Girls in Water, Sanitation, and Hygiene Policy Documents and Programs of Bangladesh and Cambodia: Content Analysis Using EquiFrame

People with disabilities and as women and girls face barriers to accessing water, sanitation, and hygiene (WASH) services and facilities that fully meet their needs, especially in low- and middle-income countries. Women and girls with disabilities experience double discrimination. WASH policies should support and uphold the concepts of disability and gender inclusion, and they should also act as a guide to inform WASH programs and service delivery. Using a modified version of the EquiFrame content analysis tool, this study investigated the inclusion of 21 core concepts of human rights of people with disabilities and women and girls in 16 WASH policy documents and seven end-line program reports from Bangladesh and Cambodia. Included documents typically focused on issues of accessibility and neglected wider issues, including empowerment and support for caregivers. The rights of children and women with disabilities were scarcely focused on specifically, despite their individual needs, and there was a disconnect in the translation of certain rights from policy to practice. Qualitative research is needed with stakeholders in Bangladesh and Cambodia to investigate the inclusion and omission of core rights of people with disabilities, and women and girls, as well as the factors contributing to the translation of rights from policy to practice.
Machine learning in dental, oral and craniofacial imaging: a review of recent progress

Artificial intelligence has been emerging as an increasingly important aspect of our daily lives and is widely applied in medical science. One major application of artificial intelligence in medical science is medical imaging. As a major component of artificial intelligence, many machine learning models are applied in medical diagnosis and treatment with the advancement of technology and medical imaging facilities. The popularity of convolutional neural network in dental, oral and craniofacial imaging is heightening, as it has been continually applied to a broader spectrum of scientific studies. Our manuscript reviews the fundamental principles and rationales behind machine learning, and summarizes its research progress and its recent applications specifically in dental, oral and craniofacial imaging. It also reviews the problems that remain to be resolved and evaluates the prospect of the future development of this field of scientific study.
Salmonella enterica Serovar Minnesota Biofilms, Susceptibility to Biocides, and Molecular Characterization

The presence of virulence genes, phylogenetic relationships, biofilm formation index (BFI), and ultrastructure in S. Minnesota at different temperatures (4, 25, and 36 °C) were analyzed. In addition, the ability of biocidal agents (chlorhexidine1%, sodium hypochlorite 1%, and peracetic acid 0.8%) to inhibit biofilms formed by 20 strains isolated from broiler slaughter plants from two Brazilian companies in 2009, 2010, and 2014 was determined. The presence of specific genes was evaluated by PCR and phylogeny between strains by pulsed-field gel electrophoresis. The BFI was determined using tryptone soy broth with 5% of chicken juice, and its structure was observed by scanning electron microscopy. The presence of specific genes indicated that S. Minnesota has the potential to cause disease in humans, adapting to adverse conditions. Temperatures of 25 and 36 °C favored biofilm formation, although at 4 °C, there was still biomass that could contaminate the final product. Tolerance to all biocides was identified in 12/20 (60%), representing a real risk of adaptation mechanisms development, especially regarding to resistance to sodium hypochlorite. Phylogenetic analysis indicated cross-contamination and spread among companies, which was probably related to biofilms formation. Results show the necessity of attention to this serovar considering its resistance to sodium hypochlorite, including the need for rigorous control, adopting low temperatures to prevent biofilms formation in the poultry industry.