Miracle-dz/UniFAR-FTUs huggingface dataset:
Progestins Related to Progesterone and Testosterone Elicit Divergent Human Endometrial Transcriptomes and Biofunctions

Progestins are widely used for the treatment of gynecologic disorders and alone, or combined with an estrogen, are used as contraceptives. While their potencies, efficacies and side effects vary due to differences in structures, doses and routes of administration, little is known about their effects on the endometrial transcriptome in the presence or absence of estrogen. Herein, we assessed the transcriptome and pathways induced by progesterone (P4) and the three most commonly used synthetic progestins, medroxyprogesterone acetate (MPA), levonorgestrel (LNG), and norethindrone acetate (NETA), on human endometrial stromal fibroblasts (eSF), key players in endometrial physiology and reproductive success. While there were similar transcriptional responses, each progestin induced unique genes and biofunctions, consistent with their structural similarities to progesterone (P4 and MPA) or testosterone (LNG and NETA), involving cellular proliferation, migration and invasion. Addition of estradiol (E2) to each progestin influenced the number of differentially expressed genes and biofunctions in P4 and MPA, while LNG and NETA signatures were more independent of E2. Together, these data suggest different mechanisms of action for different progestins, with progestin-specific altered signatures when combined with E2. Further investigation is warranted for a personalized approach in different gynecologic disorders, for contraception, and minimizing side effects associated with their use.
Development and Validation of a Medication Selection Model Under Clinical Application of Renin-Angiotensin Inhibitor Combined with Calcium Channel Blocker for Hypertension Patients

Background This study evaluated the impact of clinical features and concomitant conditions on the clinical selection of different renin-angiotensin system (RAS) inhibitors in patients with hypertension, and built a renin-angiotensin inhibitors selection model (RAISM) to provide a reference for clinical decision making. Material/Methods We included 213 hypertensive patients in the study cohort; patients were divided into two groups: the angiotensin-converting enzyme inhibitor (ACEI) combined with calcium channel blocker (CCB) group (ACEI+CCB group) and the angiotensin receptor antagonist (ARB) combined with CCB group (ARB+CCB group). Basic demographic characteristics and concomitant conditions of the patients were compared. Single-factor and multi-factor analysis was performed by adopting logistic regression model. The RAISM was established by utilizing the nomograph technology. C-index and calibration curve were used to evaluate the model’s efficacy. Results In the study, 34.27% of the patients used ACEI+CCB and 65.73% of patients used ARB+CCB. The difference in age, body mass index (BMI), elderly patient, diabetes, renal dysfunction, and hyperlipidemia between the 2 groups determined medication selection. To be specific, compared to the group using ARB+CCB, the odds ratios and 95% confidence interval (CI) of the aforementioned factors for the ACEI+CCB group were 0.476 (0.319–0.711), 1.274 (1.001–1.622), 0.365 (0.180–0.743), 0.471 (0.203–1.092), 0.542 (0.268–1.094), and 0.270 (0.100–0.728), respectively; The C-index of RAISM acquired from the model construction parameters was 0.699, and the correction curve demonstrated that the model has good discriminative ability. Conclusions The outcome of our study suggests that independent discriminating factors that influence the clinical selection of different RAS inhibitors were elderly patient, renal insufficiency, and hyperlipidemia; and the RAISM constructed in this study has good predictability and clinical benefit.
Evaluation of copromicroscopy and serology to measure the exposure to Ascaris infections across age groups and to assess the impact of 3 years of biannual mass drug administration in Jimma Town, Ethiopia

Background The scientific community has recently summarized the desired characteristics for diagnostic tools across the different phases of a soil-transmitted helminth (STH) mass drug administration (MDA) program. Although serology meets some of the desired criteria, there is a scarcity of data on baseline serological profiles in human populations, both prior to and during MDA programs. Methods In this study, we compared the copromicroscopic and the serological infection profiles in 600 school-aged children (SAC) and 600 adults at the advent of the MDA program in Jimma Town, Ethiopia. The serological profiles were examined by two ELISAs that measure IgG4 responses to the Ascaris suum haemoglobin antigen (AsHb) and a somatic extract of lung stage larvae (AsLungL3). Three years into the MDA program, we sampled another group of 600 SAC from the same schools to assess the reduction in prevalence and intensity of Ascaris infections measured by copromicroscopy and serology. Principal findings Prior to the start of MDA, copromicroscopy revealed an Ascaris prevalence of 31.0% and a mean fecal egg count of 2,919 eggs per gram (EPG) in SAC. Following three years of biannual treatment, the prevalence reduced to 13.2% (57.8% reduction) and the mean fecal egg count to 1,513 EPG (48.1% reduction). This reduction was also reflected in the serological results. The seroprevalence reduced with 40.9% and 27.4% and the mean optical density ratio reduced with 44.2% and 38.2% as measured by the AsHb or AsLungL3 ELISA respectively. We also showed that, despite a decreasing coproprevalence, seroprevalence to Ascaris increased with age. Conclusions This study is the first to provide IgG4 response profiles of an endemic population to two different A. suum antigens. The results suggest that exposure to the infectious stages of Ascaris reaches beyond SAC alone. Furthermore, it highlights the possible use of serological assays to monitor changes in STH exposure during MDA programs.
The Influence of Lip Repair on the Growth of Craniofacial Structures in Bilateral Cleft Lip and Palate Patients With Unoperated Palate From Childhood to Adulthood.

PURPOSE Surgical treatment of complete bilateral cleft lip and palate (BCLP) is the most difficult procedure among common cleft lip and palate. This study was to research the long-term effect of lip surgery by localizing the craniofacial growth pattern of BCLP patients in the Han people in western China compared with normal healthy people from childhood to adulthood. PATIENTS AND METHODS A cross-sectional study included a sample of 43 BCLP patients who have received lip repair and a control group of 55 normal healthy people with Angle Class I occlusion at the similar age, gender and ethnicity, and all participants were obtained from the Department of Oral and Maxillofacial Surgery, Sichuan University. Sixteen linear and 14 angular bony landmarks were identified on lateral cephalometric radiographs at the average age of 5.6-year-old, 10.7-year-old, and 24.2-year-old. The measurements were used to represent the growth changes of cranial base, bony nasopharynx, maxillary, mandibular and maxilla-mandibular relationship. Between-group differences were assessed by using the Independent-Sample t test. RESULT Lip repair has a slow and long-term effect on the craniofacial morphology. The tension from repaired orbicularis oris muscle would cause a decrease in maxillary sagittal length and the retroposition of maxilla combined with the mandibular functional displacement, which would cause a positive change in the postoperative facial morphology of BCLP patients in the long run. CONCLUSION BCLP patients who have undergone lip repair at an early age have the potential to develop better facial convexity.
Security problems of systems of extremely weak devices

In this paper we discuss some fundamental security issues of distributed systems of weak devices. We briefly describe two extreme kinds of such systems-the sensor network and the Radio Frequency IDentification (RFID) system from the point of view of security mechanisms designer. We describe some most important particularities and issues (including unsolved problems) that have to be taken into account in security design and analysis. Finally we present some fundamental concepts and paradigms of research on security of weak devices. In the paper we also give a brief survey of ultra-light HB/HB+-family of encryption schemes and so-called predistribution protocols.
Colistin and its role in the Era of antibiotic resistance: an extended review (2000–2019)

ABSTRACT Increasing antibiotic resistance in multidrug-resistant (MDR) Gram-negative bacteria (MDR-GNB) presents significant health problems worldwide, since the vital available and effective antibiotics, including; broad-spectrum penicillins, fluoroquinolones, aminoglycosides, and β-lactams, such as; carbapenems, monobactam, and cephalosporins; often fail to fight MDR Gram-negative pathogens as well as the absence of new antibiotics that can defeat these “superbugs”. All of these has prompted the reconsideration of old drugs such as polymyxins that were reckoned too toxic for clinical use. Only two polymyxins, polymyxin E (colistin) and polymyxin B, are currently commercially available. Colistin has re-emerged as a last-hope treatment in the mid-1990s against MDR Gram-negative pathogens due to the development of extensively drug-resistant GNB. Unfortunately, rapid global resistance towards colistin has emerged following its resurgence. Different mechanisms of colistin resistance have been characterized, including intrinsic, mutational, and transferable mechanisms. In this review, we intend to discuss the progress over the last two decades in understanding the alternative colistin mechanisms of action and different strategies used by bacteria to develop resistance against colistin, besides providing an update about what is previously recognized and what is novel concerning colistin resistance.
Reasons for Tooth Extractions and Related Risk Factors in Adult Patients: A Cohort Study

Background: The aim of this study was to evaluate oral status, the reasons for tooth extractions and related risk factors in adult patients attending a hospital dental practice. Methods: 120 consecutive patients ranging from 23 to 91 years in age (mean age of 63.3 ± 15.8) having a total of 554 teeth extracted were included. Surveys about general health status were conducted and potential risk factors such as smoking, diabetes and age were investigated. Results: a total of 1795 teeth were missing after extraction procedures and the mean number of remaining teeth after the extraction process was 16.8 ± 9.1 per patient. Caries (52.2%) was the most common reason for extraction along with periodontal disease (35.7%). Males were more prone to extractions, with 394 of the teeth extracted out of the total of 554 (71.1%). Male sex (β = 2.89; 95% CI 1.26, 4.53; p = 0.001) and smoking habit (β = 2.95; 95% CI 1.12, 4.79; p = 0.002) were related to a higher number of teeth extracted. Age (β = −0.24; 95% CI −0.31, −0.16; p < 0.001) and diabetes (β = −4.47; 95% CI −7.61, −1.33; p = 0.006) were related to a higher number of missing teeth at evaluation time. Moreover, periodontal disease was more common as a reason of extraction among diabetic patients than among non-diabetic ones (p = 0.04). Conclusions: caries and periodontal disease were the most common causes of extraction in a relatively old study population: further screening strategies might be required for the early interception of caries and periodontal disease.
MiR-139-5p influences hepatocellular carcinoma cell invasion and proliferation capacities via decreasing SLITRK4 expression

Abstract The microRNA, miR-139-5p, has been proved to play important roles in regulating tumor progression, including prostate cancer, osteosarcoma, esophageal cancer, and so on, but its correlation of hepatocellular carcinoma (HCC) still remains unclear. Here we found that hsa-miR-139-5p (miR-139-5p) was decreased in HCC samples compared with normal liver tissues, and a lower expression of miR-139-5p was connected to a poorer prognosis. Mechanism study indicated that a decreased/increased miR-139-5p could increase/decrease HCC cells invasion and proliferation capacities via increasing SLITRK4 expression, what’s more, the reverse assays also confirmed the conclusion when we knocked down SLITRK4 in the miR-139-5p low-expression cells. Luciferase assay confirmed that miR-139-5p could directly bind to the 3′UTR of SLITRK4 mRNA to regulate its expression. Together, these findings show the importance of miR-139-5p/SLITRK4 pathway in HCC growth and progression and may provide new targets for us to better arrange the progression of HCC.
Studies on the mechanosensory innervation of muscle using organotypic culture, reinnervation and immunohistochemistry

This thesis studies sensory innervation in mammals using an organotypic co-culture of spinal cord-dorsal root ganglion and skeletal muscle of embryonic rat, the histological changes of reinnervated muscle spindles after nerve section and the localisation of the calcium-binding protein calretinin in cat mechanoreceptor organs. The immediate importance of this project concerns the better understanding of how the normal process of development differs from reinnervation following nerve lesion or section. A range of classical and well defined materials and methods as been used in the work described. The thesis Is divided into Ove chapters: Chapter 1 reviews aspects of the mechanosensory organs which have been studied experimentally in relation to their sensory innervation, including proprioceptive muscle spindle development, reinnervation, and finally, the presence of the calcium-binding protein, calretinin in the mechanoreceptor organs. This provides an introduction and background to the work. Chapter 2 describes the organotypic organisation of spinal-cord, dorsal-root ganglia and skeletal muscle co-culture in vitro. Results show that slices of the spinal-cord, dorsal- root ganglia survive well under experimental conditions and can live for several weeks with feeding every 1-3 days. Sensory neurons can develop and grow in a medium without any additional promoting factor. The presence of structurally identifiable synapses indicates that other neurons are also maintained in culture and have functional connections. In the organotypic culture new muscle fibres can form either from the original explant or from the additional explant. In chapter 3 I describe two abnormal endings present in spindles of the tenuissimus of the cat that had been reinnervated following section of the nerve more than one year previously. The reconstruction of the endings of these two spindles supports the hypothesis of modulation of the primary-ending response by the mechanical properties of the intrafusal muscle fibres, rather than by intrinsic properties of the la afferent itself. They further indicate that, in the absence of a la afferent, intrafusal-fibre differentiation can be maintained by a group II afferent. Chapter 4 concerns the localisation of the calcium-binding protein calretinin, which was studied immunohistochemically in the abductor digiti quinti medius muscle of the cat hind limb. The calretinin immunoreactivity was found in some intrafusal fibres, the primary endings and the cqjsule of the muscle spindles and the sensory terminals of tendon organs and Paciniform corpuscles. The present findings contradict a recent hypothesis that calretinin is associated with rapid adaptation, but suggest that calretinin has a specific function in muscle proprioceptors. Finally, Chapter 5 outlines the conclusions of this study and gives some suggestions for continuation of the work in the future.
THE PREVALENCE OF DIABETIC RETINOPATHY

Diabetic Retinopathy is a damage retina caused by complication of diabetes mellitus. Approximately 40% of the diabetes cases tend to be retinopathy diabetic, even 8% of those cases are going to have blindness. The research aimed to describe diabetic retinopathy prevalence at H Adam Malik Hospital in Medan. The research method was retrospective descriptive and samples ware acquired from medical record during July in 2011 to June in 2012 at H Adam Malik Hospital in Medan. The findings indicated that there was no significant difference of a number of diabetic retinopathy patients between man and women. Mostly diabetic retinopathy patients were approximately 50 – 59 years old with duration of diabetes mellitus for 5 to 10 years old. The conclusion is the height of prevalence diabetic retinopathy is influenced by age and duration of diabetes mellitus.
CK1δ as a potential therapeutic target to treat bladder cancer

Bladder cancer is the second most common genitourinary malignancy in the world. However, only immune-checkpoint inhibitors and erdafitinib are available to treat advanced bladder cancer. Our previous study reported that 4-((4-(4-ethylpiperazin-1-yl) phenyl)amino)-N-(3,4,5-trichlorophenyl)-7H-pyrrolo-[2, 3-d]pyrimidine-7-carboxamide hydrochloride (13i HCl) is a potent CK1δ inhibitor showing significant anti-bladder cancer activity. In this study, we elucidated the pharmacological mechanisms underlying 13i HCl’s inhibition of human bladder cancer. Our results demonstrate that expression of the CSNK1D gene, which codes for CK1δ, is upregulated in superficial and infiltrating bladder cancer patients in two independent datasets. CK1δ knockdown decreased β-catenin expression in bladder cancer cells and inhibited their growth. Additionally, 13i HCl suppressed bladder cancer cell proliferation and increased apoptosis. We also observed that inhibition of CK1δ using 13i HCl or PF-670462 triggers necroptosis in bladder cancer cells. Finally, 13i HCl inhibited bladder cancer cell migration and reversed their mesenchymal characteristics. These findings suggest further development of 13i HCl as a potential therapeutic agent to treat bladder cancer is warranted.
Population Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target Attainment

Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1). The initial dose of 8, 12, or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). ABSTRACT Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1). The initial dose of 8, 12, or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). Piperacillin concentrations were compared to the EUCAST clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/PD targets were evaluated: 100% free time (fT) > 1× MIC and 100% fT > 4× MIC. A population pharmacokinetic model was developed using NONMEM 7.4. 3 consisting of a one-compartment disposition model with linear elimination separated into nonrenal and renal (linearly increasing with patient CRCL) clearances. Target attainment was predicted and visualized for all individuals based on the utilized CRCL dosing algorithm. The target of 100% fT > 1× MIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% fT > 4× MIC. Probability of target attainment for a simulated cohort of patients showed that increasing the daily dose by 4-g increments (piperacillin component) did not result in substantially improved target attainment for the 100% fT > 4× MIC target. To conclude, in patients with high CRCL combined with high-MIC bacterial infections, even a continuous infusion (CI) regimen with a daily dose of 24 g may be insufficient to achieve therapeutic concentrations.
Diagnosis and Management of Obstructive Sleep Apnea: A Review.

Importance Obstructive sleep apnea (OSA) affects 17% of women and 34% of men in the US and has a similar prevalence in other countries. This review provides an update on the diagnosis and treatment of OSA. Observations The most common presenting symptom of OSA is excessive sleepiness, although this symptom is reported by as few as 15% to 50% of people with OSA in the general population. OSA is associated with a 2- to 3-fold increased risk of cardiovascular and metabolic disease. In many patients, OSA can be diagnosed with home sleep apnea testing, which has a sensitivity of approximately 80%. Effective treatments include weight loss and exercise, positive airway pressure, oral appliances that hold the jaw forward during sleep, and surgical modification of the pharyngeal soft tissues or facial skeleton to enlarge the upper airway. Hypoglossal nerve stimulation is effective in select patients with a body mass index less than 32. There are currently no effective pharmacological therapies. Treatment with positive airway pressure lowers blood pressure, especially in patients with resistant hypertension; however, randomized clinical trials of OSA treatment have not demonstrated significant benefit on rates of cardiovascular or cerebrovascular events. Conclusions and Relevance OSA is common and the prevalence is increasing with the increased prevalence of obesity. Daytime sleepiness is among the most common symptoms, but many patients with OSA are asymptomatic. Patients with OSA who are asymptomatic, or whose symptoms are minimally bothersome and pose no apparent risk to driving safety, can be treated with behavioral measures, such as weight loss and exercise. Interventions such as positive airway pressure are recommended for those with excessive sleepiness and resistant hypertension. Managing asymptomatic OSA to reduce cardiovascular and cerebrovascular events is not currently supported by high-quality evidence.
Environmental control on the distribution of metabolic strategies of benthic microbial mats in Lake Fryxell, Antarctica

Ecological theories posit that heterogeneity in environmental conditions greatly affects community structure and function. However, the degree to which ecological theory developed using plant- and animal-dominated systems applies to microbiomes is unclear. Investigating the metabolic strategies found in microbiomes are particularly informative for testing the universality of ecological theories because microorganisms have far wider metabolic capacity than plants and animals. We used metagenomic analyses to explore the relationships between the energy and physicochemical gradients in Lake Fryxell and the metabolic capacity of its benthic microbiome. Statistical analysis of the relative abundance of metabolic marker genes and gene family diversity shows that oxygenic photosynthesis, carbon fixation, and flavin-based electron bifurcation differentiate mats growing in different environmental conditions. The pattern of gene family diversity points to the likely importance of temporal environmental heterogeneity in addition to resource gradients. Overall, we found that the environmental heterogeneity of photosynthetically active radiation (PAR) and oxygen concentration ([O2]) in Lake Fryxell provide the framework by which metabolic diversity and composition of the community is structured, in accordance with its phylogenetic structure. The organization of the resulting microbial ecosystems are consistent with the maximum power principle and the species sorting model.