anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Early-life tobacco exposure serves as a non-negligible risk factor for aging-related diseases. To understand the underlying mechanisms, we explored the associations of early-life tobacco exposure with accelerated biological aging and further assessed the joint effects of tobacco exposure and genetic susceptibility. Compared with those without in utero exposure, participants with in utero tobacco exposure had an increase in Klemera-Doubal biological age (KDM-BA) and PhenoAge acceleration of 0.26 and 0.49 years, respectively, but a decrease in telomere length of 5.34% among 276,259 participants. We also found significant dose-response associations between the age of smoking initiation and accelerated biological aging. Furthermore, the joint effects revealed that high-polygenic risk score participants with in utero exposure and smoking initiation in childhood had the highest accelerated biological aging. There were interactions between early-life tobacco exposure and age, sex, deprivation, and diet on KDM-BA and PhenoAge acceleration. These findings highlight the importance of reducing early-life tobacco exposure to improve healthy aging.
Overdosage of chlordiazepoxide and amitriptyline hydrochloride tablets, which contains a benzodiazepine (chlordiazepoxide) and a tricyclic antidepressant (amitriptyline hydrochloride), may manifest signs and symptoms related to either of its components. Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose.   
  
Critical manifestations of tricyclic antidepressant overdosage include cardiac dysrhythmias, severe hypotension, convulsions and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Obtain an ECG and immediately initiate cardiac monitoring; hospital monitoring is required as soon as possible.   
  
Other signs of overdosage may include confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia or any of the symptoms listed under ADVERSE REACTIONS.   
Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal (see WARNINGS: Abuse, Misuse, and Addiction). Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage.   
  
In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures with chlordiazepoxide and amitriptyline hydrochloride tablets because overdosage with amitriptyline and other tricyclic and tetracyclic antidepressants increases the risk of seizures. Seizure risk is also increased in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use also may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus).   
  
Contact the Poison Help line (1-800-222-1222) or medical toxicologist for additional overdosage management recommendations.
Patients receive selinexor PO on days 1, 8 and 15, capecitabine PO twice daily (BID) on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients can continue single agent selinexor until disease progression.
Primary liver cancer (hepatocellular carcinoma or HCC) is the fifth most common cancer worldwide. Surgery to remove the tumour remains the principal form of treatment for liver cancer, however recurrence of the disease after surgery is common and survival after recurrence is poor. At the moment there is no recommended standard treatment for HCC immediately after the tumour has been removed surgically. PI-88 is a new experimental drug which blocks the growth of new blood vessels in tumours to stop the tumour growing (starves it of food) and also stops tumour cells spreading. Previous experience with PI-88 has shown it has been well tolerated and has shown some benefit in delaying the time it takes for the hepatocellular carcinoma to reappear after surgery. The purpose of this study is to determine if PI-88 is effective and safe in patients who have had surgery to remove primary liver cancer.
TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory processes of RA, polyarticular JIA, PsA, and AS and the resulting joint pathology. In addition, TNF plays a role in the inflammatory process of PsO. Elevated levels of TNF are found in involved tissues and fluids of patients with RA, JIA, PsA, AS, and PsO.

Two distinct receptors for TNF (TNFRs), a 55 kilodalton protein (p55) and a 75 kilodalton protein (p75), exist naturally as monomeric molecules on cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNFR.

Etanercept is a dimeric soluble form of the p75 TNF receptor that can bind TNF molecules. Etanercept inhibits binding of TNF-α and TNF-β (lymphotoxin alpha [LT-α]) to cell surface TNFRs, rendering TNF biologically inactive. In in vitro studies, large complexes of etanercept with TNF-α were not detected and cells expressing transmembrane TNF (that binds Enbrel) are not lysed in the presence or absence of complement.
PURPOSE:To enable effective treatment of malignant tumor, etc., by administering fragmented protein A produced by the enzymatic treatment of protein A originated from Staphylococcus aureus Cowan I strain. CONSTITUTION:Protein A originated from Staphylococcus aureus Cowan I strain is subjected to enzymatic treatment (e.g. with trypsin) and the obtained fragmented protein A is administered for treatment of malignant tumor, etc. The fragmented protein A is composed of 5 kinds of polypeptides A, B, C, D and E. Since the above polypeptides have relatively low molecular weight (i.e. <=10,000), it can be administered to blood causing little allergic reaction which is supposed to be caused by administration of protein originated from microbial cell. The necrosis, fibrillation or contraction of the tumor tissue of malignant tumor was found by administration of the fragmented protein.
Accuracy in the evaluation of death-induced tissue degradation for thanato-chronological purposes is strictly dependent on the condition of the biological source as well as on the precision of post-mortem interval (PMI) estimation. Thus, the optimization of tissue handling and identification of sensitive post-mortem biomarkers could help establish a timeline for post-mortem events. To this aim, we investigated the proteome changes in cortex samples of 6-week-old female SAMR1 mice over a post-mortem time course. After death, brain tissue was removed immediately (T0), and after 4, 8, 12, 24, and 32 h, four mice were used for each time period, and animals were maintained at 4 °C until brain removal. Dissected tissues were frozen at -80 °C until processed. Proteomic analysis, performed on samples related to early and late PMIs (<24 h and >24 h post-mortem, respectively) showed protein level changes as compared to T0 samples, with a remarkable increase in Calpain11 in the early PMI, as well as in Caspases 7 and 8 together with Gasdermin 3 in late PMI. These findings were confirmed by LIFT mass spectrometry technology and western blot analysis and, although requiring further investigation in other biological samples, suggest that these proteins could be considered as putative biomarkers of different PMIs.
The microglia overactivation-induced neuroinflammation is a significant cause of the brain injury after intracerebral hemorrhage (ICH). Iron homeostasis is crucial for microglia activation, but the mechanism and causality still need further study. This study aimed to explore the roles and mechanism of the mitochondrial iron transporter SLC25A28 in microglia activation after ICH. Intrastriatal injection of autologous blood was used to establish ICH model, and the neuroinflammation, iron metabolism and brain injuries were assessed in wildtype or microglia-specific SLC25A28 knockout mice after ICH. Mitochondria iron levels and microglial function were determined in SLC25A28 overexpressed or deleted microglia. The extracellular acidification rate (ECAR), lactate production, and glycolytic enzyme levels were used to determine aerobic glycolysis. The results showed that ICH stimulated mitochondrial iron overload, and synchronously upregulated the SLC25A28 expression. In vitro, SLC25A28 overexpression increased mitochondrial iron levels in microglia. Interestingly, microglial SLC25A28 deficiency ameliorated neuroinflammation, brain edema, blood-brain barrier injury and ethological alterations in mice after ICH. Mechanically, SLC25A28 deficiency inhibited microglial activation by restricting the aerobic glycolysis. Moreover, zinc protoporphyrin could reduce SLC25A28 expression and mitigated brain injury. SLC25A28 plays crucial roles in mitochondrial iron homeostasis and microglia activation after ICH, and it might be a potential therapeutic target for ICH.
Participants with HER2-positive LABC will receive T-DM1 3.6 mg/kg Iv infusion, docetaxel 60/75 mg/m\^2 IV infusion, and pertuzumab 840 mg (for Cycle 1) or 420 mg (for remaining cycles) IV infusion on Day 1 of each 3-week cycle, for 6 cycles. Study treatment will be administered for up to 6 cycles or until unacceptable toxicity, and prior to surgery.
Several studies have demonstrated a correlation between neurodegenerative diseases (NDDs) and myocardial infarction (MI), yet the precise causal relationship between these remains elusive. This study aimed to investigate the potential causal associations of genetically predicted Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and multiple sclerosis (MS) with MI using two-sample Mendelian randomization (TSMR). Various methods, including inverse variance weighted (IVW), weighted median (WM), MR-Egger regression, weighted mode, and simple mode, were employed to estimate the effects of genetically predicted NDDs on MI. To validate the analysis, we assessed pleiotropic effects, heterogeneity, and conducted leave-one-out sensitivity analysis. We identified that genetic predisposition to NDDs was suggestively associated with higher odds of MI (OR_IVW=1.07, OR_MR-Egger=1.08, OR_WM=1.07, OR_weighted mode=1.07, OR_simple mode=1.10, all P<0.05). Furthermore, we observed significant associations of genetically predicted DLB with MI (OR_IVW=1.07, OR_MR-Egger=1.11, OR_WM=1.09, OR_weighted mode=1.09, all P<0.05). However, there was no significant causal evidence of genetically predicted PD and MS in MI. Across all MR analyses, no horizontal pleiotropy or statistical heterogeneity was observed (all P>0.05). Additionally, results from MRPRESSO and leave-one-out sensitivity analysis confirmed the robustness of the causal effect estimations for genetically predicted AD, DLB, PD, and MS on MI. This study provides further support for the causal effects of AD on MI and, for the first time, establishes robust causal evidence for the detrimental effect of DLB on the risk of MI. Our findings emphasize the importance of monitoring the cardiovascular function of the elderly experiencing neurodegenerative changes.
The invention relates to compounds with the formulawhere the substituted have the meanings listed in the description,and to their pharmaceutically acceptable salts. They are formsintensifying the secretion of the growth hormone (secretagogues)and raising the levels of endogenous growth hormone. The compoundsare useful for the treatment and prevention of osteoporosis,congestive cardiac insufficiency and weakness related to old ageand obseity, acceleration of the strengthening of the ostealfracture, reduction of theprotein catabolytic reactions after aserious operation, reduction of the cachexia and theloss ofprotein as a result of chronic diseases, acceleration of thehealing of wounds or of the restoration of burn patients or suchundergoing a heavy operation, improvement of the muscularstrength, mobility, maintainance of the skin thickness,metabolytic homeostasis and renal homeostasis. The compounds canalso be used for the treatment of osteoporosis when applied incombination with a bisphosphonate compound such as alendronate,estrogen, premarin and optionally progesteron, estrogen agonistare antagonist, or calcitonin and useful to this pharmaceuticalcompositions. The invention also relates to pharmaceuticalcompositions which are useful for increasing the endogenousproduction or release of the growth hormon in humans or animalsthe compositions of which contain an effectiv_ _(_above compoundand form, intensifying the growth hormone secretion selected amongGHRP-6, Hexarelin, GHRP-1, factor of releasing the growth hormone(GRF), IGF-1, IGF-2, B-HT920. The invention also relates tointermediate compounds useful for the preparation of the compoundshaving the above formula.111 claims
1.Technical Result Production of physiologically active poly¬ethylene glycol-interferon alpha conjugate with improved antiproliferative properties, increase in immunomodulatory and antiviral activity of the pharmaceutical composition.           2. Essence Physiologically active polyethylene glycol-interferon-alpha conjugate represents the compounds of the general formula: 	    wherein R and Rare independently lower alkyl; X is NH or O; n and n  are integers having a sum of from 600 to 1500; and the average molecular weight of the polyethylene glycol units in said conjugate is from about 26.000 daltons to about 66.000 daltons which is obtained by covalenty linking polyethylene glycol to interferon-alpha at pH 8-9 of the reaction mixture at temperature 4C.    Pharmaceutical composition having immuno¬modu¬latory and antiviral actifity comprises said conjugate in effective amount and therapeutically acceptable additive.         3. Field of Application Organic chemistry, pharmacology.        2 ind. cl., 4 Tables,         6 fig.
An objective method for assessing speech audibility is essential to evaluate hearing aid benefit in children who are unable to participate in hearing tests. With consonant-vowel syllables, brainstem-dominant responses elicited at the voice fundamental frequency have proven successful for assessing audibility. This study aimed to harness the neural activity elicited by the slow envelope of the same repetitive consonant-vowel syllables to assess audibility. In adults and children with normal hearing and children with hearing loss wearing hearing aids, neural activity elicited by the stimulus /su∫i/ or /sa∫i/ presented at 55-75 dB SPL was analyzed using the temporal response function approach. No-stimulus runs or very low stimulus level (15 dB SPL) were used to simulate inaudible conditions in adults and children with normal hearing. Both groups of children demonstrated higher response amplitudes relative to adults. Detectability (sensitivity; true positive rate) ranged between 80.1 and 100%, and did not vary by group or stimulus level but varied by stimulus, with /sa∫i/ achieving 100% detectability at 65 dB SPL. The average minimum time needed to detect a response ranged between 3.7 and 6.4 min across stimuli and listener groups, with the shortest times recorded for stimulus /sa∫i/ and in children with hearing loss. Specificity was >94.9%. Responses to the slow envelope of non-meaningful consonant-vowel syllables can be used to ascertain audible vs. inaudible speech with sufficient accuracy within clinically feasible test times. Such responses can increase the clinical usefulness of existing objective approaches to evaluate hearing aid benefit.
Children adopted internationally by parents in the United States often experience institutional care prior to adoption. Early institutional care may lead to inattention, deficits in inhibitory control, and insecure attachments in children. Many of these problems persist even after the child is adopted. This study will test the effectiveness of a parent training program called Attachment and Biobehavioral Catch-up for Children Adopted Internationally (ABC-I). This program is designed to enhance children's ability to regulate their attention, behavior, and physiology and to develop secure, organized attachments to their parents.

Participation in this study will begin when the child participant is between 12 and 20 months old, and it will end when the child is 4 years old. Participants, who will include parents and their adopted child, will meet with the study researchers 3 times before receiving the training program intervention, twice in their home and once at the research site. During these visits, the background and medical history of the child participant will be reviewed. Participants will then be randomly assigned to receive 1 of 2 parent training programs: ABC-I or Developmental Education for Families (DEF). Both programs will involve 10 weekly sessions, each lasting 60 to 90 minutes and occurring in the parents' homes. The DEF training program will focus on enhancing the intellectual and language development of the child participant, but it will not train parents to pay attention to and interpret their children's cues. The ABC-I training program will involve videotaping parents while they interact with their children, reviewing the videotapes, discussing strategies for interacting with children, and completing homework assignments.

Participants will undergo assessments before and after the training programs and at follow-up visits when each child turns 2, 3, and 4 years old. Assessments will be made of sensitivity in parents and of inattention, inhibitory control, attachment quality, and cortisol production in children. Parent sensitivity will be measured by observing parent-child interactions and coding them according to a pre-existing scale. Child inattention and inhibitory control will be measured through observing each child's behaviors on various structured tasks, such as watching a video with a distracter present or being told to wait to open a wrapped gift. Attachment will be measured through observation of child behavior and through parent ratings and diaries. Cortisol production will be measured through a saliva sample, collected via cotton swab. When children are 4 years old, they will also be evaluated for diagnosable behavioral disorders. For a subset of children, cheek swabs will be collected at age 5-6 for the assessment of telomere length.
The present invention provides a polynucleotide (ipka) which identifies and encodes a novel human cAMP-dependent protein kinase A inhibitor homolog (IPKA). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding IPKA. The invention also provides for the use of purified IPKA and its agonists in the commercial production of recombinant proteins and in pharmaceutical compositions for the treatment of diseases associated with the expression of IPKA. Additionally, the invention provides for the use of antisense molecules to ipka in pharmaceutical compositions for treatment of diseases associated with the expression of IPKA. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotide, fragments or the complement thereof, which hybridize with the genomic sequence or the transcript of ipka. The present invention also relates to anti-IPKA antibodies which specifically bind to IPKA.
PURPOSE:To obtain an amino acid composition for oral administration capable of improving nitrogen metabolism in hepatic or renal diseases, by compounding an amino acid selected from cystine, cysteine and methionine with alanine, aspartic acid and glycine at specific ratios. CONSTITUTION:The objective amino acid composition can be produced by compounding (A) 32.0-48.0pts.wt. of an amino acid selected from cystine, cysteine, methionine and their mixture based on 100pts.wt. of total amino acid, (B) 14.0-20.7pts.wt. of alanine, (C) 18.7-28.0pts.wt. of aspartic acid and (D) 15.5-23.4pts.wt. of glycine. Especially preferable amino acid composition is 0.5pt.wt. of glycine, 0.4pt.wt. of alanine and 0.6pt.wt. of asparagine based on 1pt.wt. of cystine. The composition improves nitrogen metabolism, lowers ammonia level in blood, promotes synthesis of serum albumin, increases serum cholesterol, lowers ZTT value, promotes reutilization of free hemoglobin and improves various symptoms in hepatic and renal diseases.
Numerous studies have reported that self-reported short sleep duration is associated with obesity and weight gain. Insufficient sleep may be one of the most common, and most preventable, obesity risk factors. Given that sleep restriction is largely voluntary and potentially correctable, understanding the mechanisms that link insufficient sleep to positive energy balance and the development of obesity, particularly visceral obesity, is crucial to clinical applications, public health policy, and informing future studies. The investigators wish to determine whether 14 nights of modest sleep restriction results in increased energy balance, thus potentially increasing the risk of obesity. The investigators will combine energy balance, biomarker, and imaging data with state-of-the art sleep monitoring to provide unambiguous data on the effects of sleep restriction on obesity. Together, the investigators findings will help explain whether the reduced sleep duration in the general population may be contributing to the current epidemic of obesity, and suggest strategies to reduce this risk.
A pharmaceutical prepn (I) which is not phagocyted and which can be used for parenteral or mucous membrane application of sparingly soluble active ingredients consists of a dispose solid/liq. system with max. particle size of the active ingredient 3 micron. These particles have a coating of starch, starch components or starch derivs obtd. by retrogradation. USE/ADVANTAGE - (I) can be used with cytostatics, antibiotics, heart/circulation agents or spironolactone as the active ingredient. The small particles of active ingredient can be completely enclosed by the aggregates produced by the retrogradation, in comparison to larger particles, where the coating is not uniform and has holes, thus giving rise to some aggregates which contain no active ingredient nucleus. The body is not able to identify the solid active ingredient particles as foreign, and they are thus not phagocyted and eliminated from the system. The coating is completely biologically acceptable.