anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology. The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis. Here, we recapitulated the complexity of the renin-angiotensin system, discussed the role of hepatic stellate cell (HSC) autophagy in liver fibrogenesis, and analyzed the possible implications in the development of hepatocarcinoma (HCC). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis, whereas their involvement in HCC is more evident in experimental conditions than in human studies. Angiotensin-converting enzyme 2 (ACE2), and its product Angiotensin (Ang) 1-7, not only regulate HSC autophagy and liver fibrosis, but they also represent potential targets for unexplored applications in the field of HCC. Finally, ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. In this case, Ang 1-7 acts binding to the MasR, and its agonists could modulate this pathway. However, since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively, we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.
This project will use neuroimaging (7T MRI: structural, diffusion and rest-state functional MRI), from Dr. Noam Harel's protocol IRB# STUDY00008096, and non-invasive brain stimulation (TMS: PAS. SAI) techniques to quantify structural and functional changes in brain function. The TMS experiment will use a Magstim Bistimn 2002 transcranial magnetic stimulation (TMS) unit and standard figure-of-eight coil (70 mm diameter) to deliver stimulation on the surface of the scalp. Stimulation will be delivered using either a single pulse or with a paired-pulse protocol (two stimuli, through the same TMS coil at inter-stimulus intervals of 50 or 80 ms). All surface EMG signals will be pre-amplified within the sensor and sent wirelessly via blue-tooth connection to a Delsys data collection system. Quantitative assessments of motor function (gait, gait initiation, reactive balance, bradykinesia, repetitive alternating movements, rigidity, stop-signal reaction time), and neuropsychological function will used to assess behavioral status at baseline and 30-36 months later.
The control arm will be a retrospective chart review of patients ages 6 to 21 who present to the pediatric emergency department with sickle cell VOC listed as one of their diagnoses with the aim of identifying pain scores in accordance with medications received and identifying final disposition and identifying time in the emergency department and time to ED disposition. We aimed to review 100 charts. We found that 84 met inclusion criteria.
Protein replacement therapy for patients with hemophilia or other inherited protein deficiencies is often complicated by pathogenic antibody responses, including antibodies that neutralize the therapeutic protein or that predispose to potentially life-threatening anaphylactic reactions by formation of IgE. Using murine hemophilia B as a model, we have developed a prophylactic protocol against such responses that is non-invasive and does not include immune suppression or genetic manipulation of the patient's cells. Oral delivery of coagulation factor IX (F. IX) expressed in chloroplasts, bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies in protein replacement therapy. Inhibitor titers were mostly undetectable and up to 100-fold lower in treated mice when compared to controls. Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after 4 to 6 exposures to intravenous F. IX protein. While only 20-25% of control animals survived after 6-8 F. IX doses, 90-95% of tolerized mice survived 12 injections without signs of allergy or anaphylaxis. This high-responder strain of hemophilia B mice represents the first hemophilic animal model to study anaphylactic reactions. The plant material was effective over a range of oral antigen doses (equivalent to 5-80 μg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months. Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach to oral delivery of protein antigens to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.
Insertion of 25 mg PGE1 (Prostaglandin E1) tablet is inserted in the posterior fornix. The patient woll the be instructed to stay in bed for the next 60 minutes. After six hours a repeated dose will be administered. Total of 4 PGE1 doses within 24 hours.
Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
PCT No. PCT/JP93/01262 Sec. 371 Date May 6, 1994 Sec. 102(e) Date May 6, 1994 PCT Filed Sep. 7, 1993 PCT Pub. No. WO94/05696 PCT Pub. Date Mar. 17, 1994.Novel peptide derivatives having RGD as a basic structure were found which have a platelet aggregation-inhibiting action, blood coagulation-inhibiting action and cell adhesion-inhibiting action. Utlizing these effects of the peptide derivatives, the following agents which comprise the peptides as active ingredients were provided: platelet aggregation-inhibiting agents that are effective in thrombolus during and after the treatment of thrombolysis and thromboembolism and that can further prevent reobstruction and cardiac infarction; blood coagulation-inhibiting agents that can inhibit blood coagulation which is the main cause of thrombus formation during extracorporeal circulation; cell adhesion-inhibiting agents; tumor metastasis-inhibiting agents; and agents for protecting platelet preparations for blood transfusion. In addition, the present invention intends to provide platelet preparation packs for blood transfusion, characterized in that the peptide dervatives are contained in platelet preparations for blood transfusion in packs.
Risk Summary

Based on findings from animal studies and their mechanism of action [see Clinical Pharmacology (12.1)], bevacizumab products may cause fetal harm in pregnant women. Limited postmarketing reports describe cases of fetal malformations with use of bevacizumab products in pregnancy; however, these reports are insufficient to determine drug-associated risks. In animal reproduction studies, intravenous administration of bevacizumab to pregnant rabbits every 3 days during organogenesis at doses approximately 1 to 10 times the clinical dose of 10 mg/kg produced fetal resorptions, decreased maternal and fetal weight gain and multiple congenital malformations including corneal opacities and abnormal ossification of the skull and skeleton including limb and phalangeal defects (see Data). Furthermore, animal models link angiogenesis and VEGF and VEGFR2 to critical aspects of female reproduction, embryofetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

Pregnant rabbits dosed with 10 mg/kg to 100 mg/kg bevacizumab (approximately 1 to 10 times the clinical dose of 10 mg/kg) every three days during the period of organogenesis (gestation day 6–18) exhibited decreases in maternal and fetal body weights and increased number of fetal resorptions. There were dose-related increases in the number of litters containing fetuses with any type of malformation (42% for the 0 mg/kg dose, 76% for the 30 mg/kg dose, and 95% for the 100 mg/kg dose) or fetal alterations (9% for the 0 mg/kg dose, 15% for the 30 mg/kg dose, and 61% for the 100 mg/kg dose). Skeletal deformities were observed at all dose levels, with some abnormalities including meningocele observed only at the 100 mg/kg dose level. Teratogenic effects included: reduced or irregular ossification in the skull, jaw, spine, ribs, tibia and bones of the paws; fontanel, rib and hindlimb deformities; corneal opacity; and absent hindlimb phalanges.
A new pharmaceutical and cosmetic preparation contains as active ingredients 0.01-2 wt. % glycerol trinitrate and 0.1-10 wt. % of at least one polyunsaturated fatty acid selected from gamma-linolenic acid, linoleic acid or a physiologically active salt or derivative thereof, in a physiologically acceptable carrier. The prepn. is used for treatment of psoriasis, seborrhoea and cosmetic conditions. The active component have the ability to react with oxygen free radicals. (Provisional Basic previously advised in week 9007).
Chronic kidney disease (CKD) is a global public health problem. The prevalence of CKD in adults in China was 10.8%. Awareness of CKD is only 10.04% from a national cross-sectional survey in China. CKD is characterised by decreased estimated glomerular filtration rate (eGFR) and increased albuminuria, present for more than three months, and is associated with adverse outcomes (all-cause mortality, acute kidney injury, and end-stage renal disease), independent of hypertension and diabetes, age, or sex. CKD may carry a coronary heart disease risk similar to that of diabetes. The estimated lifetime risk of CKD stage 3a was more than 50%, lower than that of hypertension (83%-90% for a 55-year-old), but higher than those for diabetes (33%-39%), coronary heart disease (32%-49% for a 40-year-old), and invasive cancer (38%-45%).

Albuminuria measurement and estimating glomerular filtration rate (GFR) are the primary means of screening for CKD in epidemiological investigations. However, there are many important problems to be solved, whether albuminuria test or GFR evaluation. The investigators aim to detect thrice albumin-creatinine ratio (ACR) within three months, with simultaneous test of urinary protein-creatinine ratio (PCR), 24-hour urine protein excretion rate (PER) and 24-hour albumin excretion rate (AER) to compare the effects of different times of screening for CKD and observe the daily physiological variation of ACR, PCR, AER and PER, and repeat test to reduce the physiological variation, and further derive ACR and PCR reference value on the basis of different genders, in order to facilitate the early diagnosis of CKD. Meanwhile, for more accurate assessment of GFR in Chinese populations, the investigators intend to validate beta-trace protein (BTP) based equation to evaluate GFR compared with 99mTc-diethylenetriamine pentaacetic acid (DTPA) renal clearance method. Then the investigators aim to develop GFR estimation equation based on the combination of serum creatinine, cystatin C, β2-microglobulin and BTP applicable in China, for early and accurate assessment of GFR in Chinese people, and develop appropriate software to estimating GFR.
Diabetes mellitus (DM) is a highly prevalent disease worldwide, estimated to affect 1 in every 11 adults; among them, 90-95% of cases are type 2 diabetes mellitus. This is partly attributed to the surge in the prevalence of obesity, which has reached epidemic proportions since 2008. In these patients, cardiovascular (CV) risk stands as the primary cause of morbidity and mortality, placing a substantial burden on healthcare systems due to the potential for macrovascular and microvascular complications. In this context, leptin, an adipocyte-derived hormone, plays a fundamental role. This hormone is essential for regulating the cellular metabolism and energy balance, controlling inflammatory responses, and maintaining CV system homeostasis. Thus, leptin resistance not only contributes to weight gain but may also lead to increased cardiac inflammation, greater fibrosis, hypertension, and impairment of the cardiac metabolism. Understanding the relationship between leptin resistance and CV risk in obese individuals with type 2 DM (T2DM) could improve the management and prevention of this complication. Therefore, in this narrative review, we will discuss the evidence linking leptin with the presence, severity, and/or prognosis of obesity and T2DM regarding CV disease, aiming to shed light on the potential implications for better management and preventive strategies.
BACKGROUND: While free jejunum transfer (FJT) following total pharyngo-laryngo-esophagectomy (TPLE) is a reliable reconstruction technique, the jejunum flap is viewed as more susceptible to ischemia than a standard free flap. Animal studies have indicated that the jejunum can tolerate ischemia for as little as 2 to 3 hours. Clinical studies also reported increased complications after the FJT with more than 3 hours of ischemia. Traditionally, our institution has carried out FJT with an initial intestinal anastomosis, followed by a vascular anastomosis, which often results in extended jejunal ischemia time. In this study, we retrospectively examined the actual tolerance of the jejunum to ischemia, considering perioperative complications and postoperative dysphagia.
METHODS: We retrospectively studied 402 consecutive cases involving TPLE + FJT. Patients were divided into five groups based on jejunum ischemia time (∼119 minutes, 120∼149 minutes, 150∼179 minutes, 180∼209 minutes, 210 minutes∼), with each variable and result item compared between the groups. Univariate and multivariate analyses were conducted to identify independent factors influencing the four results: three perioperative complications (pedicle thrombosis, anastomotic leak, surgical site infection) and dysphagia at 6 months postoperatively.
RESULTS: The mean jejunal ischemia time was 164.6 ± 28.4 (90-259) minutes. When comparing groups divided by jejunal ischemia time, we found no significant differences in overall outcomes or complications. Our multivariate analyses indicated that jejunal ischemia time did not impact the three perioperative complications and postoperative dysphagia.
CONCLUSION: In TPLE + FJT, a jejunal ischemia time of up to 4 hours had no effect on perioperative complications or postoperative dysphagia. The TPLE + FJT technique, involving a jejunal anastomosis first followed by vascular anastomosis, benefits from an easier jejunal anastomosis but suffers from a longer jejunal ischemia time. However, we found that ischemia time does not pose significant problems, although we have not evaluated the effects of jejunal ischemia extending beyond 4 hours.
The Echopulse System provides High Intensity Focused Ultrasound (HIFU) ablation of soft tissue. The energy is delivered via an extra-corporeal treatment probe, which includes an imaging system. The high-energy ultrasound waves propagate through the skin and are focused on a portion of the target tissue, generating intense heat and causing local cell apoptosis and progressive tissue volume reduction over the following months in the tissue within the focal area. The process is then repeated in a stepwise fashion to destroy the targeted tissues.

The Echopulse System is comprised of several components, including the console, treatment arm containing the visualization and treatment unit (VTU), and computer with touchscreen user interface. In addition, the Echopulse System is intended to be used in conjunction with a disposable cooling and coupling system known as EPack.

This is a single-center prospective study with a planned accrual of 35 patients with diagnosed symptomatic Lower Limb Veins System (Superficial, Perforating) Insufficiency (including recurrence at the thigh/groin level after previous treatment). The eligible patients must present a symptomatic Leg Veins System Insufficiency diagnosis which fulfills the inclusion/exclusion criteria. All patients will be consented at a Pre-Study Visit and evaluated for eligibility and for baseline characteristics of the disease. Patients will return to clinic on a separate day for the HIFU treatment. Device performance parameters will be collected during the HIFU visit. At follow-up visits at 3 days, 7 days and 3 months, changes in veins and flow characteristics will be evaluated by ultrasound and physical exam, and patient well-being, including pain and anxiety, will be evaluated by patient-reported VAS evaluations. Continued follow-up for a total of 3 months will be completed prior to subject study exit. Adverse events (AE) will be assessed at every study visit following HIFU treatment. An interim Safety Report will be issued after the first 5 patients will arrive at the 7 days visit and will be provided to the Ethics Committee. A second report will be issued once the first 5 patients will complete the follow-up period of 30 days and will be also provided to the Ethics Committee.
BACKGROUND: Cerebral palsy (CP) is a condition resulting from perinatal brain injury and can lead to physical disabilities. Exosomes derived from human amniotic mesenchymal stromal cells (hAMSC-Exos) hold promise as potential therapeutic options.
OBJECTIVE: This study aimed to investigate the impact of hAMSC-Exos on neuronal cells and their role in regulating apoptosis both in vitro and in vivo.
METHODS: hAMSC-Exos were isolated via ultracentrifugation and characterized via transmission electron microscopy, particle size analysis, and flow cytometry. In vitro, neuronal damage was induced by lipopolysaccharide (LPS). CP rat models were established via left common carotid artery ligation. Apoptosis levels in cells and CP rats were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, and TUNEL analysis.
RESULTS: The results demonstrated successful isolation of hAMSC-Exos via ultracentrifugation, as the isolated cells were positive for CD9 (79.7%) and CD63 (80.2%). Treatment with hAMSC-Exos significantly mitigated the reduction in cell viability induced by LPS. Flow cytometry revealed that LPS-induced damage promoted apoptosis, but this effect was attenuated by treatment with hAMSC-Exos. Additionally, the expression of caspase-3 and caspase-9 and the Bcl-2/Bax ratio indicated that excessive apoptosis could be attenuated by treatment with hAMSC-Exos. Furthermore, tail vein injection of hAMSC-Exos improved the neurobehavioral function of CP rats. Histological analysis via HE and TUNEL staining showed that apoptosis-related damage was attenuated following hAMSC-Exo treatment.
CONCLUSIONS: In conclusion, hAMSC-Exos effectively promote neuronal cell survival by regulating apoptosis, indicating their potential as a promising therapeutic option for CP that merits further investigation.
The brain and cardiovascular system share common risk factors for age-related diseases such as hypertension, hypercholesterolemia, and genetics (e.g. APOE4). Because of this link, much work has focused on the role of cerebrovascular health in reducing dementia risk. Regular aerobic exercise has well-established benefits for cardiovascular health and has been repeatedly linked to better cognition, brain health, and lower risk of Alzheimer's disease (AD). Despite strong evidence for sustained cognitive and brain outcomes, the mechanisms relating aerobic exercise with brain health and cognition remain imprecisely defined. Amongst many potential mechanisms, cerebral blood flow (CBF) and blood-based biomarkers, such as neurotrophins, are promising targets for their shared association to brain and cardiovascular health. Prior investigations have largely attempted to measure change in these mechanisms under resting conditions after an extended exercise intervention with mixed and conflicting results. Further, studies have often not accounted for genetic differences that may blunt the effect of exercise. Unlike prior work, our innovative approach is to begin by characterizing the dynamic changes that result from an acute exercise challenge. A single bout of aerobic exercise temporarily increases CBF and prompts neurotrophin release. These transient changes ultimately drive long-term physiologic adaptation to exercise. Therefore, the study team will characterize the dynamic response to an acute, standardized bout of aerobic exercise in a group of nondemented older adults, comparing those who do and do not carry the APOE4 allele. The first aim will test if CBF response to an acute exercise challenge is blunted in APOE4 carriers. The second aim will similarly test the acute exercise response of blood-based biomarkers such as brain derived neurotrophic factor, insulin-like growth factor, and vascular endothelial growth factor in APOE4 carriers versus non-carriers. The study team expects that more accurately understanding the acute effects will provide valuable insight into how aerobic exercise supports cognitive function and brain health. Armed with this knowledge the field can optimize biomarker measurement for future exercise intervention randomized controlled trials, informing our long-term goal of identifying precision exercise prescription for AD prevention.
INTRODUCTION: One billion people live with obesity. The most promising medications for its treatment are incretin-based therapies, based on enteroendocrine peptides released in response to oral nutrients, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The mechanisms by which GLP-1 receptor agonism cause weight reduction are becoming increasingly understood. However, the mechanisms by which GIP receptor-modulating medications cause weight loss remain to be clarified.
AREAS COVERED: This review describes GLP-1 and GIP physiology and explores the conflicting data regarding GIP and weight management. It details examples of how to reconcile the contradictory findings that both GIP receptor agonism and antagonism cause weight reduction. Specifically, it discusses the concept of 'biased agonism' wherein exogenous peptides cause different post-receptor signaling patterns than native ligands. It discusses how GIP effects in adipose tissue and the central nervous system may cause weight reduction. It describes GIP receptor-modulating compounds and their most current trials regarding weight reduction.
EXPERT OPINION: Effects of GIP receptor-modulating compounds on different tissues have implications for both weight reduction and other cardiometabolic diseases. Further study is needed to understand the implications of GIP agonism on not just weight reduction, but also cardiovascular disease, liver disease, bone health and fat storage.