anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Perinatal white matter injury (WMI) is the leading cause of long-term neurological morbidity in infants born preterm. Neuroinflammation during a critical window of early brain development plays a key role in WMI disease pathogenesis. The mechanisms linking inflammation with the long-term myelination failure that characterizes WMI, however, remain unknown. Here, we investigate the role of astrocyte reactivity in WMI. In an experimental mouse model of WMI, we demonstrate that WMI disease outcomes are improved in mutant mice lacking secretion of inflammatory molecules TNF-α, IL-1α, and C1q known, in addition to other roles, to induce the formation of a neuroinflammatory reactive astrocyte substate. We show that astrocytes express molecular signatures of the neuroinflammatory reactive astrocyte substate in both our WMI mouse model and human tissue affected by WMI, and that this gene expression pattern is dampened in injured mutant mice. Our data provide evidence that a neuroinflammatory reactive astrocyte substate correlates with adverse WMI disease outcomes, thus highlighting the need for further investigation of these cells as potential causal players in WMI pathology.
FIELD: chemistry. ^ SUBSTANCE: invention relates to a group of compounds of general formula (I) (where substitute Q-A is on a ring atom, which is separated by two atoms from the ring atom directly bonded to the substituted glucitol group), where R1, R2, R3 and R4 are each independently selected from hydrogen, -C(=O)Rx and alkyl, which can be substituted with one or more Ra, where Ra is phenyl and Rx is alkyl; Ar1 is a benzene ring which can be substituted with alkyl or halogen, a thiophene ring or pyrazine ring; Q is -(CH2)m-(L)p-; m is an integer from 0 to 2, n is equal to 1 or 2, p is equal to 0 or 1; L is -O-, A is a phenyl which can be substituted with one or more Rb, naphthyl or a 5-10-member aromatic heterocyclic group containing a nitrogen or sulphur atom; Rb is independently selected from alkenyl, alkynyl, halogen, hydroxyl, cyano group, carboxyl group, alkoxy group, which can be substituted with one or more Rc, phenyl, alkylthio group, alkylsulphonyl group, -NRfRg, alkylcarbonyl group, alkoxycarbonyl group, alkylenedioxy group, pyrazolyl group and tetrahydrofuranyloxy group; Re is independently selected from halogen, hydroxyl and phenyl; Rf is hydrogen and Rg is alkylcarbonyl, or pharmaceutically acceptable salts thereof. The invention also relates to a group of specific compounds having general formula (I). The invention also pertains to a group of intermediate compounds of compounds of general formula (Ib), which are used in synthesis of compounds of formula (Ia) (special case of formula I). The invention also relates to pharmaceutical compositions based on compounds of formula (I) for use as an inhibitor or Na+-glucose II cotransporter, as well as for use in preventing or treating diabetes, hyperglycemia, caused by hyperglycemia of diabetic complications, or obesity. The invention also relates to a method of preventing or treating diabetes caused by hyperglycemia of diabetic complications or obesity by administering a therapeutically effective amount of the compound of formula (I) to a patient. ^ EFFECT: high effectiveness of the compounds. ^ 15 cl, 10 tbl, 48 ex
Acetaminophen (APAP, also known as paracetamol) is a commonly used antipyretic and analgesic that is considered safe to use during pregnancy. However, a growing body of research indicates that gestational administration of APAP increased the risk of neurodevelopmental, reproductive and genitourinary disorders in offspring, alongside impairments in placental development. Notably, over-dosed APAP exhibits direct toxicity to endothelial cells, but there is very limited research investigating the impact of APAP on placental angiogenesis, a gap we aim to address in this study. Pregnant mice were gavaged with APAP (15, 50 and 150 mg/kg/d) from embryonic day 11.5 (E11.5) to E13.5. Administration of 150 mg/kg/d APAP leads to low birth weight (LBW) of the offspring and disordered vascular structures within the labyrinthine (Lab) layer of the placenta. This disruption is accompanied by a significant increase in Suppressor of Cytokine Signaling 3 (SOCS3) level, a negative regulator of the Janus kinase signal transducer 1 and activator of the transcription 3 (JAK1/STAT3) signaling. Meanwhile, Human umbilical vein endothelial Cells (HUVECs) with the treatment of 3 mM APAP exhibited reduced cell viability, whereas 1 mM APAP significantly affected the proliferation, migration, invasion and angiogenic capacities of HUVECs. Further, SOCS3 was up-regulated in HUVECs, accompanied by inhibition of JAK1/STAT3 pathways. Knocking-down SOCS3 in HUVECs restored the nuclear translocation of STAT3 and efficiently promoted cellular capacity of tube formation. Overall, short-term maternal administration of overdosed APAP impairs angiogenic capacities of fetal endothelial cells via SOCS3/JAK1/STAT3 pathway in the mouse placenta. This study reveals that overdose of APAP during pregnancy may adversely affect placental angiogenesis, emphasizing the importance of adhering to the safe principles of smallest effective dose for the shortest required durations.
OBJECTIVE: We conducted a community-based cohort study to predict the 3-year occurrence of chronic kidney disease (CKD) among population aged ≥60 years.
METHOD: Participants were selected from two communities through randomized cluster sampling in Jiading District of Shanghai, China. The two communities were randomly divided into a development cohort (n = 12012) and a validation cohort (n = 6248) with a 3-year follow-up. Logistic regression analysis was used to determine the independent predictors. A nomogram was established to predict the occurrence of CKD within 3 years. The area under the curve (AUC), the calibration curve and decision curve analysis (DCA) curve were used to evaluate the model.
RESULT: At baseline, participants in development cohort and validation cohort were with the mean age of 68.24 ± 5.87 and 67.68 ± 5.26 years old, respectively. During 3 years, 1516 (12.6%) and 544 (8.9%) new cases developed CKD in the development and validation cohorts, respectively. Nine variables (age, systolic blood pressure, body mass index, exercise, previous hypertension, triglycerides, fasting plasma glucose, glycated hemoglobin and serum creatinine) were included in the prediction model. The AUC value was 0.742 [95% confidence interval (CI), 0.728-0.756] in the development cohort and 0.881(95%CI, 0.867-0.895) in the validation cohort, respectively. The calibration curves and DCA curves demonstrate an effective predictive model.
CONCLUSION: Our nomogram model is a simple, reasonable and reliable tool for predicting the risk of 3-year CKD in community-dwelling elderly people, which is helpful for timely intervention and reducing the incidence of CKD.
BACKGROUND: Oxygen therapy plays a pivotal role in treating critically ill patients in the intensive care unit (ICU). However, excessive oxygen concentrations can precipitate hyperoxia, leading to damage in multiple organs, with a notable effect on the lungs. Hyperoxia condition may lead to hyperoxia-induced acute lung injury (HALI), deemed as a milder form of acute respiratory distress syndrome (ARDS). Given its clinical importance and practical implications, there is a compelling need to investigate the underlying pathogenesis and comprehensively understand the regulatory mechanisms implicated in the development of HALI.
RESULTS: In this study, we conducted a mouse model with HALI and performed regulatory mechanism analysis using RNA-seq on both HALI and control group. Comprehensive analysis revealed 727 genes of significant differential expression, including 248 long non-coding RNAs (lncRNAs). Also, alternative splicing events were identified from sequencing results. Notably, we observed up-regulation or abnormal alternative splicing of genes associated with immune response and ferroptosis under hyperoxia conditions. Utilizing weighted gene co-expression network analysis (WGCNA), we ascertained that genes involved in immune response formed a distinct cluster, showcasing an up-regulated pattern in hyperoxia, consistent with previous studies. Furthermore, a competing endogenous RNA (ceRNA) network was constructed, including 78 differentially expressed mRNAs and six differentially expressed lncRNAs, including H19. These findings uncover the intricate interplay of multiple transcriptional regulatory mechanisms specifically tailored to the pulmonary defense against HALI, substantiating the importance of these non-coding RNAs in this disease context.
CONCLUSIONS: Our results provide new insights into the potential mechanisms and underlying pathogenesis in the development of HALI at the post-transcriptional level. The findings of this study reveal potential regulatory interactions and biological roles of specific lncRNAs and genes, such as H19 and Sox9, encompassing driven gene expression patterns, alternative splicing events, and lncRNA-miRNA-mRNA ceRNA networks. These findings may pave the way for advancing therapeutic strategies and reducing the risk associated with oxygen treatment for patients.
During the premarketing development of SUBVENITE, 20 sudden and unexplained deaths were recorded among a cohort of 4,700 patients with epilepsy (5,747 patient-years of exposure).

Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at night. This represents an incidence of 0.0035 deaths per patient-year. Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained death in epilepsy (SUDEP) in patients not receiving SUBVENITE (ranging from 0.0005 for the general population of patients with epilepsy, to 0.004 for a recently studied clinical trial population similar to that in the clinical development program for SUBVENITE, to 0.005 for patients with refractory epilepsy). Consequently, whether these figures are reassuring or suggest concern depends on the comparability of the populations reported upon with the cohort receiving SUBVENITE and the accuracy of the estimates provided. Probably most reassuring is the similarity of estimated SUDEP rates in patients receiving SUBVENITE and those receiving other AEDs, chemically unrelated to each other, that underwent clinical testing in similar populations. This evidence suggests, although it certainly does not prove, that the high SUDEP rates reflect population rates, not a drug effect.
Traumatic brain injury (TBI) is a highly prevalent medical condition for which no medications specific for the prophylaxis or treatment of the condition as a whole exist. The spectrum of symptoms includes coma, headache, seizures, cognitive impairment, depression, and anxiety. Although it has been known for years that the inhibitory neurotransmitter γ-amino-butyric acid (GABA) is involved in TBI, no novel therapeutics based upon this mechanism have been introduced into clinical practice. We review the neuroanatomical, neurophysiological, neurochemical, and neuropharmacological relationships of GABA neurotransmission to TBI with a view toward new potential GABA-based medicines. The long-standing idea that excitatory and inhibitory (GABA and others) balances are disrupted by TBI is supported by the experimental data but has failed to invent novel methods of restoring this balance. The slow progress in advancing new treatments is due to the complexity of the disorder that encompasses multiple dynamically interacting biological processes including hemodynamic and metabolic systems, neurodegeneration and neurogenesis, major disruptions in neural networks and axons, frank brain lesions, and a multitude of symptoms that have differential neuronal and neurohormonal regulatory mechanisms. Although the current and ongoing clinical studies include GABAergic drugs, no novel GABA compounds are being explored. It is suggested that filling the gap in understanding the roles played by specific GABAA receptor configurations within specific neuronal circuits could help define new therapeutic approaches. Further research into the temporal and spatial delivery of GABA modulators should also be useful. Along with GABA modulation, research into the sequencing of GABA and non-GABA treatments will be needed.
The invention involves a computer system which implements an array of symbols on a screen which is accessible to a community of users such as the users of the World Wide Web (WWW). The web site generated provides each user with a screen which shows a plurality of possible medical tests (represented by the symbols) which the user may self administer. The medical tests may require answers to questions, responses to sound and/or determining the users response to symbols presented on the screen and/or perceived or actual changes in those symbols. The medical tests can be completely unrelated, related in part, or completed interrelated as a series dependent on each other. The results of the tests are analyzed by the system and provided to the user and/or others. The medical tests can provide information on the users physical and/or mental condition and results can be provided with recommendations to seek medical treatment.
BACKGROUND: In 1992 the American College of Sports Medicine first described the Female Athlete Triad. The Triad is a metabolic injury involving three distinct clinical traits: low energy availability, with possible eating disorder, low bone mineral density and menstrual dysfunction (MD). Although the estimated prevalence of the Triad is low (1.2 %), single factors are common in female athletes, at all competitive levels and ages. Even though the Triad was described over two decades ago, the interrelation of the three diagnostics components is still debated: additional evidence is required to improve the multidisciplinary treatment approach for this complex condition. MD is one of the first signs of energy impairment. The present study aims at investigating MD determinants and predictors in female athletes, to allow an early diagnosis of the Triad and to implement adequate preventive strategies.
MATERIALS AND METHODS: An original structured questionnaire was composed to detect the presence of MD risk factors. Included participants were active female athletes within reproductive age range (15-40 years old). Anthropometric parameters and training-related factors, possibly affecting the regularity of the menstrual cycle, were investigated.
RESULTS: Respondents were 288 female athletes. Among them, 73.3 % were under 25 years of age; 6.6 % resulted underweight; 30.6 % reported to follow a meal plan/diet and 13.9 % declared to be a smoker. Lean sports were practiced by 30.6 % of responders. Body-weight congruence was detected in in 79.9 % of participants, whereas overestimation of body image was found in 16.3 % of athletes. Irregular menstrual cycle, a possible MD predictor, was present in 33.0 % of athletes, with 41.1 % practicing some lean sport (p = 0.007). Also, overestimation of body image suggested an increased risk of menstrual irregularity (p = 0.001). BMI <18.5 or BMI >30 could also act as risk factor, although significance was not fully obtained (p = 0.053). Overall, practice of lean sports and overestimation of body image appeared good determinants of increased menstrual irregularity (AOR 2.02 and 3.83, respectively).
CONCLUSIONS: Menstrual irregularity in female athletes can be considered an early predictor of MD: risk is further increased in athletes of lean sports and reporting an overestimation of self-perceived body image. Screenings and awareness programs should specifically address female athletes, because of their vulnerable-group profile. In order to define a standardized at-risk profile for Triad onset and sequelae likelihood, evaluation of menstrual regularity should especially be considered, in conjunction with the assessment of other indicators of energy availability (e.g. TEE, lean and fat mass, BMC). Testing for sport-derived stress and disordered eating attitudes is also recommended. Preventive strategy should involve the proactive engagement of sport clubs and periodic competitive sport medical assessment.
The participants will complete a 4-minute constant work rate treadmill test with a basic, portable fan placed in front of the face. The fan will be placed at a location to target the second and third branches of the trigeminal nerve and will be placed a distance chosen by the participant so that the airflow speed is comfortable.
FIELD: chemistry of heterocyclic compounds. SUBSTANCE: product: derivatives of quinoline-2-yl-methoxybenzylhydroxyurea of the formula (I)  . Reaction conditions: interaction of corresponding compound of the formula (II)   with hydroxylamine hydrochloride in the medium of inert solvent in the presence of base and synthesis of compound of the formula (III)  . The latter then is reduced and subjected for interaction with trialkylallylisocyanate. EFFECT: improved method of synthesis. 5 cl
BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China.
PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed.
RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%.
CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.
Patients admitted in intensive care unit for 3 days. Administration of the lowest inspiratory fraction dose of oxygen to maintain oxygen peripheral saturation (SpO2) between 94 and 98% or an arterial partial pressure of oxygen (PaO2) between 70 and 100 mmHg. No oxygen addition administer for transports or diagnostic manoeuvres. Conventional clinical criteria for airways control and ventilation technique.
When intranasal corticosteroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of fluticasone propionate nasal spray should be discontinued slowly consistent with accepted procedures for discontinuing oral corticosteroid therapy.

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. In addition, some patients may experience symptoms of corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression). Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause a severe exacerbation of their symptoms.
BACKGROUND AND OBJECTIVES: Blood establishments strive to ensure the safety and comfort of blood donors while minimizing adverse events. This review aims to assess the efficacy and effectiveness of eating and/or drinking interventions before, during and/or after blood donation in reducing vasovagal reactions (VVRs).
MATERIALS AND METHODS: We analysed randomized and non-randomized controlled trials comparing eating and/or drinking interventions to no intervention, placebo or usual practice on (pre-)syncopal VVRs and related symptoms. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess the risk of bias and overall certainty of the evidence.
RESULTS: Pre-donation water ingestion likely results in reduced on-site VVRs, compared to no water (2 fewer per 100 donors, moderate-certainty evidence). A pre-donation isotonic drink likely results in reduced VVRs, compared to usual practice (2 fewer per 100 donors, moderate-certainty evidence). Pre-donation salt-loaded sweetened lemon water may result in fewer off-site VVRs, compared to sweetened lemon water only (1 fewer per 100 donors, low-certainty evidence). Pre-donation water and a gel cap containing sucrose with 250 mg caffeine may result in fewer blood donor reaction ratings, compared to pre-donation water only (low-certainty evidence).
CONCLUSIONS: Pre-donation plain water ingestion or isotonic drink probably results in a large reduction in on-site and off-site VVRs. Pre-donation water ingestion with caffeine consumption or salt supplementation may result in a VVR reduction, compared to water ingestion only. Future large trials are required to increase the certainty of the effect of these and other interventions in the prevention of VVRs.
BACKGROUND AND AIM: Several studies reported osteolysis around polyethylene glycol/polybutylene terephthalate (PEG/PBT) based femoral cement restrictors. Our goal was to evaluate and compare osteolysis around 3 different plug designs: the slow biodegradable PEG/PBT cement restrictor; the fast biodegradable gelatin cement restrictor; and the non-biodegradable polyethylene plug.
PATIENTS AND METHODS: In a retrospective multicentre cohort study chart data were extracted of patients who received a total hip arthroplasty between 2008 and 2012. A total of 961 hips were included. Cortical ratio between inner and outer cortices at the centre of the plug was measured on routine postoperative follow-up moments. Median follow up of all 3 hospitals was 3.5 years (1.4-7.3). The primary outcome was evidence of osteolysis (i.e. the difference in cortical ratio [CR]) on anteroposterior (AP) radiographs at final follow-up.
RESULTS: Progressive osteolysis was found around the PEG/PBT cement restrictor represented by a significantly increasing cortical ratio (ΔCR 0.067 (95% CI, 0.063-0.071). Distance from tip prosthesis to plug and size of the plug were found to be independent factors in predicting increased cortical ratio.
CONCLUSIONS: Our multicentre cohort shows increase of cortical ratio around the PEG/PBT cement restrictor which progresses over time. Physicians should be aware of this fact and are advised to intensify follow-up of patients who received this cement restrictor.
If severe sepsis with suspected DIC is diagnosed, the Heparin sodium(2ml:12500 units) will be administered intravenously continuously for 24 hours. The course of treatment will last 7 days or until the death or discharge.