anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Pre-emptive pharmacogenomic testing will be implemented in clinical sites across seven European countries (United Kingdom, The Netherlands, Austria, Greece, Slovenia, Italy and Spain). The 36-month study is split into two (19 and 18-month) time-blocks. The participating countries are randomized to start with either implementing pharmacogenomics guided prescribing or with standard of care in the first block. In the pharmacogenomics guided prescribing arm, results of the pharmacogenomic test will be incorporated in the (electronic) medical record and may be used by physicians and pharmacists to guide drug and dose selection for 39 routinely prescribed drugs, as per the Dutch Pharmacogenomics Working Group guidelines. In the standard of care arm, patients will not receive pharmacogenomic testing. After this 19-month block, the countries switch to implementing the opposite strategy and will recruit new patients for a period of 18 months.

Patients are eligible for participation when they receive a first prescription for one or more of 39 drugs for which a Dutch Pharmacogenomic Working Group guideline is available (acenocoumarol, amitriptyline, aripiprazole, atomoxetine, atorvastatin, azathioprine ,capecitabine, citalopram, clomipramine, clopidogrel, codeine, doxepin, efavirenz, escitalopram, flecainide, flucloxacillin, fluorouracil, haloperidol, imipramine, irinotecan, mercaptopurine, metoprolol, nortryptiline, paroxetine, phenprocoumon, phenytoin, pimozide, propafenon, sertraline, simvastatin, tacrolimus, tamoxifen, tegafur, thioguanine, tramadol, venlafaxine, voriconazole, warfarin or zuclopenthixol). All patients will be followed for a minimum of three months and a maximum of 18 months. In total, 8,100 patients will be recruited; 4,050 will receive pharmacogenomic testing, and 4,050 will receive standard of care. Each implementation site will concentrate on, but is not limited to, recruiting patients within a specific therapeutic area. Therapeutic areas include primary care, general medicine, cardiology, oncology, psychiatry, neurology, and transplantation. It is hypothesized that implementing pharmacogenomics guided drug and dose selection will decrease incidence of clinically relevant adverse drug reactions by 30% (from 4% to 2.8% among those with actionable drug-gene interactions).
The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of sulindac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see Drug Interactions).

Avoid the use of sulindac tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If sulindac tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
BACKGROUND: The prevalence of non-small cell lung cancer (NSCLC) is notably elevated in individuals diagnosed with idiopathic pulmonary fibrosis (IPF). Secreted phosphoprotein 1 (SPP1), known for its involvement in diverse physiological processes, including oncogenesis and organ fibrosis, has an ambiguous role at the intersection of IPF and NSCLC. Our study sought to elucidate the function of SPP1 within the pathogenesis of IPF and its subsequent impact on NSCLC progression.
METHODS: Four GEO datasets was analyzed for common differential genes and TCGA database was used to analyze the prognosis. The immune infiltration was analyzed by TIMER database. SPP1 expression was examined in human lung tissues, the IPF fibroblasts and the BLM-induced mouse lung fibrosis model. Combined with SPP1 gene gain- and loss-of-function, qRT-PCR, Western blot, EdU and CCK-8 experiments were performed to evaluate the effects and mechanisms of SPP1 in IPF progression. Effect of SPP1 on NSCLC was detected by co-cultured IPF fibroblasts and NSCLC cells.
RESULTS: Through bioinformatics analysis, we observed a significant overexpression of SPP1 in both IPF and NSCLC patient datasets, correlating with enhanced immune infiltration of cancer-associated fibroblasts in NSCLC. Elevated levels of SPP1 were detected in lung tissue samples from IPF patients and bleomycin-induced mouse models, with partial colocalization observed with α-smooth muscle actin. Knockdown of SPP1 inhibits TGF-β1-induced differentiation of fibroblasts to myofibroblasts and the proliferation of IPF fibroblasts. Conversely, SPP1 overexpression promoted IPF fibroblast proliferation via PI3K/Akt/mTOR pathway. Furthermore, IPF fibroblasts promoted NSCLC cell proliferation and activated the PI3K/Akt/mTOR pathway; these effects were attenuated by SPP1 knockdown in IPF fibroblasts.
CONCLUSIONS: Our findings suggest that SPP1 functions as a molecule promoting both fibrosis and tumorigenesis, positioning it as a prospective therapeutic target for managing the co-occurrence of IPF and NSCLC.
OBJECTIVE: To evaluate the clinical effect of retroaural injection of methylprednisolone sodium succinate combined with hyperbaric oxygen (HBO) on the treatment of noise-induced hearing loss.
METHODS: Case data of 220 patients with hearing loss treated at the Zhongda Hospital Southeast University from January 1, 2019 to August 1, 2023 were obtained. As per the treatment plan, the recruited patients were divided into two cohorts: 158 cases in the combined-treatment group (retroaural injection of methylprednisolone sodium succinate combined with HBO) and 62 cases in the single-hormone group (retroaural injection of methylprednisolone sodium succinate). Comparison of the clinical efficacies and postoperative complication rates of the two groups was performed after treatment. MS-Excel was used to build a database for all data, and SPSS26.0 was utilized in the statistical analysis of recorded data.
RESULTS: For patients with low-frequency, high-frequency, and flat descending type, the combined-treatment group showed significantly higher clinical effective rate than the single-hormone group (P < 0.05). For patients with disease duration ≤7 days, the combined-treatment group attained a significantly higher clinical effective rate was than the single-hormone group (P < 0.05). The safety of patients in both groups was evaluated mainly through their adverse reactions. The total incidence of adverse reactions in the single-hormone group reached 9.68%, and that in the combined-treatment group was 8.23%. The two groups revealed no significant difference in terms of incidence of adverse reactions (P > 0.05).
CONCLUSION: HBO combined with retroaural injection of methylprednisolone sodium succinate has good clinical efficacy and safety in the treatment of hearing loss.
Multiple Sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease leading to focal and diffuse damage of myelin sheath and axons in the central nervous system (CNS). Pathophysiologically, the adaptive and innate immune system are involved in the inflammatory process, while mitochondrial dysfunction, oxidative stress and failure of remyelination are important mechanisms leading to chronic neurodegeneration. Despite currently available disease modifying treatments (DMTs) that target the immune system, patients continue to accumulate disability. Unfortunately, no neuroprotective or remyelinating agents are available to treat progressive MS. Hence, drugs to tackle disease progression in MS represent a major unmet need. In this respect, metformin is a very interesting drug to investigate in MS patients as a neuroprotective and remyelinating therapy. Several preclinical studies in animal models of MS have shown that metformin has both anti-inflammatory, neuroprotective and remyelinating properties. A clinical study with metformin in a limited sample of MS patients did not demonstrate significant adverse events. The aim of this clinical trial is to provide evidence for the neuroprotective and remyelinating effects of metformin (I) in MS patients (P) via measurement of clinical and MRI outcome measures (O), via a multicentre randomized placebo-controlled (C) clinical trial.
To evaluate the genetics of chronic nonsuppurative otitis media (OM). We performed a genome-wide association study of 429,599 individuals included in the FinnGen study using three different case definitions: combined chronic nonsuppurative OM (7034 cases) (included serous and mucous chronic OM), mucous chronic OM (5953 cases), and secretory chronic OM (1689 cases). Individuals without otitis media were used as controls (417,745 controls). We used immunohistochemistry (IHC) of the murine middle ear to evaluate the expression of annexin A13. Four loci were significantly associated (p < 1.7 × 10-8) with nonsuppurative OM. Three out of the four association signals included missense variants in genes that may play a role in otitis media pathobiology. According to our subtype-specific analyses, one novel locus, located near ANXA13, was associated with secretory OM. Three loci (near TNFRSF13B, GAS2L2, and TBX1) were associated with mucous OM. Immunohistochemistry of murine middle ear samples revealed annexin A13 expression at the apical pole of the Eustachian tube epithelium as well as variable intensity of the secretory cells of the glandular structure in proximity to the Eustachian tube. We demonstrated that secretory and mucous OM have distinct and shared genetic associations. The association of GAS2L2 with ciliary epithelium function and the pathogenesis of dysfunctional mucosa in mucous OM is suggested. The abundant expression of annexin A13 in the Eustachian tube epithelium, along with its role in apical transport for the binding and transfer of phospholipids, indicates the role of annexin A13 and phospholipids in Eustachian tube dysfunction.
There will be 400 adults with moderate or severe methamphetamine use disorder randomized into this multi-site study. Eligibility will be determined during a maximum 21 day screening period. After screening is completed and eligibility is confirmed, including successful administration of a naloxone challenge, participants will begin the 12 week medication phase of the trial. Participants will be randomized to either the 1) AMC arm and receive injections of extended release naltrexone (XR-NTX; as Vivitrol®) plus once-daily oral extended-release bupropion tablets (BUP-XL) or the 2) matching placebo (PLB) arm and receive injections of placebo (iPLB) plus once-daily oral placebo (oPLB) tablets. During the course of the study, participants may be switched to another arm, as determined by the a priori adaptive aspect of the study design. Participants appearing to respond well to their original treatment assignment will not be switched. Overall, approximately 50% of the participants will receive the AMC. Injections will be administered every three weeks, in weeks 1, 4, 7, and 10. Take-home oral study medication (BUP-XL or oPLB) will be dispensed weekly for dosing on non-clinic days. Participants will be asked to attend the clinic twice weekly for observed oral medication dosing, assessments, collection of urine samples, and once-weekly medical management. On non-clinic days, participants will participate in smartphone app-based medication adherence activities. Participants will be asked to complete assessments as indicated on the schedule of assessments. Following the 12 week medication phase, participants will complete a follow-up phase, including a medication taper and post-medication phase follow-up visits during weeks 13 and 16.
BACKGROUND: Complications after abdominoplasty remain an unsolved issue in body contouring surgery. The antifibrinolytic drug tranexamic acid (TXA) has gained increasing recognition as a valuable pharmacologic agent within plastic surgery. The aim of this study was to investigate the influence of intravenously administered TXA on complications and patient safety after abdominoplasty.
METHODS: Within this retrospective single-center study, patients who underwent abdominoplasty and received intravenous TXA were selected and compared to randomly selected patients who underwent abdominoplasty without administration of TXA. The patient population was divided into two study groups (TXA vs no TXA). Demographic and surgical data as well as complications were evaluated and compared. Appropriate statistical analysis was performed.
RESULTS: Fifty-seven female and 3 male patients with a median age of 38 years and a mean BMI of 25.6 ± 3.3 kg/m2 were included in the study. Except smoking history, demographic data showed no statistically significant differences between both groups. The most common complication was seroma formation (n = 16; 23.9%), and its occurrence was statistically significantly lower in the TXA group (p = 0.023). Furthermore, postoperative seroma aspiration was performed in statistically significant lower numbers in the TXA group (p < 0.05). No thromboembolic events or seizures were observed.
DISCUSSION: The outcomes of this study showed that the intravenous administration of TXA leads to a significant reduction of seroma formation and postoperative seroma aspiration after abdominoplasty. Simultaneously, no adverse thromboembolic events were detected. Hence we would recommend administration of TXA in body contouring surgery to decrease the incidence of seroma formation.
LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Patients in the acupressure group will be given acupressure once a day for 7 consecutive days. Acupressure application will be applied by researchers who have been trained and certified on this subject. While the patients are in supine position, pressure will be applied to each acupressure point around the navel, respectively, Zhongwan (CV12), Guanyuan (CV4) and Tianshu (ST25) for 2 minutes for a total of 6 minutes.
It is described a drug delivery system ( 100 ) that is adapted to infuse at least one drug in a profile related to the status of a patient. The system comprises sensors ( 110 ), dedicated electronics ( 140 ) and software to monitor the patient's activity and maintain control over the drug-release profile. A control unit ( 120 ) of the system ( 100 ) is adapted to temporarily set at least one component ( 110, 120, 150 ) of the system ( 100 ) in an idle mode ( 265 ). This will result in particular in a reduction of power required by the system ( 100 ). The described system ( 100 ) enables a personalized treatment of patients by monitoring their individual activity status and coupling this information to a drug delivery following appropriate delivery profiles. The system ( 100 ) may be provided with a memory in order to store a time dependence of activity data. This time dependence may be used by physicians to monitor, support and adapt their therapy for the patients. The system ( 100 ) may be realized as a closed-loop system for monitoring and treatment of various diseases such as hemophilia A and Parkinson.
Patients received angiotensin-converting enzyme inhibitor/angiotensin receptor blockers treatment the first 6 months. The following 6 months patients received angiotensin receptor neprilysin inhibitor treatment.
INTRODUCTION: This study investigated the impact of the shared intertwin circulation in unequally divided monochorionic (MC) placentas on fetal growth.
METHODS: This retrospective analysis included color-dyed, unequally shared placentas from two tertiary centers. Exclusions included twin-twin transfusion syndrome, twin anemia polycythemia sequence, and lethal anomalies. Measurement of the external diameters and areas of the artery-to-artery (AA), artery-to-vein (AV), and vein-to-vein (VV) anastomoses was performed. The ratio of the shared circulation (AV ratio) was determined by comparing the areas of the summed venous components of shared AV anastomoses to those in the individual AV anastomoses of the smaller placental part. The birth weight ratio/placental ratio (BWR/PR), total AV size areas and net AV transfusion were calculated. Univariable and multivariable linear regressions were performed to assess the relationship between BWR/PR, the AV ratio, the areas of the different anastomoses and cord insertion discordance.
RESULTS: Among 352 placentas, 97 % (340) had intertwin AV anastomoses, and 50 % (176) were from pregnancies with selective growth restriction. The AV ratio, AA, VV, total AV areas, and cord insertion discordance negatively correlated with BWR/PR. Multivariable linear regression confirmed the independent negative association between BWR/PR and the AV ratio, suggesting that a larger shared circulation benefits the twin with the smaller placental part. Type III sFGR placentas exhibited the highest AV ratio, resulting in the lowest BWR/PR.
DISCUSSION: A larger shared circulation mitigates the impact of an unequally divided placenta on fetal growth. This effect surpasses the influence of AA and VV diameters and is most prominent in Type III sFGR placentas.
The main objective of this trial is to assess the efficacy and safety of propranolol in middle cerebral artery stroke patients. The primary hypothesis is as follows: Early administration of propranolol reduces the frequency of cardiovascular and/or neurological complications including vascular death in the first 30 days after acute ischemic stroke. Secondary hypotheses are as follows: Early administration of propranolol improves neurological and functional outcome of patients with acute ischemic stroke. Early administration of propranolol reduces post-stroke immunodepression and therefore lowers the rate of pneumonia after acute ischemic stroke, without increasing the frequency of auto-aggressive, CNS antigen-specific T cells. Early administration of propranolol influences alterations in cardiologic, electrophysiologic phenomenons as a reaction to autonomic dysregulation after acute ischemic stroke. Early administration of Propranolol reduces growth of infarct as determined by MRI examinations in the first 6 days.
BACKGROUND: Postoperative infection is a devastating complication in limb salvage surgery for malignant soft tissue tumors. The low absolute case numbers of these rare cancers represent a bottleneck for data collection and analysis. The administration of nationwide registry data is a practical option for the accumulation of cases.
METHODS: Data on malignant soft tissue tumor resection were extracted from the Bone and Soft Tissue Tumor Registry in Japan. The incidence of postoperative infection and its risk factors were analyzed.
RESULTS: A total of 14,460 cases were included. The incidence of infection was 2.6%. Significant risks for infection were male sex, lower extremity or trunk location, tumor diameter of over 10 cm, trans-compartmental invasion, high grade, autologous bone graft, myocutaneous flap, vascular reconstruction, reconstruction by prosthesis, postoperative radiotherapy, and delayed wound healing.
CONCLUSIONS: The incidence was lower than those in the previous studies, perhaps because of less frequent radiotherapy application. Some of the significant risk factors represented local invasiveness of the tumor, suggesting the importance of the preservation of soft tissue for infection prevention. The administration of nationwide registry data was informative for the analysis of infection in malignant soft tissue tumor resection.
The effectiveness of raxibacumab is based solely on efficacy studies in animal models of inhalational anthrax. It is not ethical or feasible to conduct controlled clinical trials with intentional exposure of humans to anthrax [see Clinical Studies (14.1)].

Safety and pharmacokinetics (PK) of raxibacumab have been studied in adult healthy volunteers. There have been no trials of safety or PK of raxibacumab in the pediatric population. An extrapolation approach was used to derive dosing regimens that are predicted to provide pediatric patients with exposure comparable to the observed exposure in adults [see Use in Specific Populations (8.4)].

Raxibacumab binds to the protective antigen (PA) of B. anthracis; it does not have direct antibacterial activity. Raxibacumab does not cross the blood-brain barrier and does not prevent or treat meningitis. Raxibacumab should be used in combination with appropriate antibacterial drugs.
It has been recently established that brown adipose tissue (BAT) exists in adult humans. BAT is a thermogenic tissue which dissipates energy as heat. The primary objective of this study is to use thermal imaging to assess the effect of capsinoids on BAT activity in adult humans, and whether there is a relationship between the increase in energy expenditure and BAT activity after capsinoids intake. The secondary objective is to investigate whether capsinoids will have an effect on an individual's glycaemic response. Lean, healthy male volunteers will be recruited. There will be two test sessions which are randomized, where subjects will consume either capsinoids or placebo capsules, and a standardized amount of white rice (equivalent to 50g carbohydrates). Indirect calorimetry will be used to assess energy expenditure before and after consumption of the test meal. Thermal imaging of supraclavicular BAT, the primary BAT depot in humans, will be undertaken using an infrared thermal camera to assess changes in BAT temperature. Blood glucose levels will be monitored by finger prick blood sampling method. This study aims to investigate whether capsinoids consumption leads to changes in BAT temperatures detectable by the infrared thermal camera, to confirm the feasibility of using thermal imaging as a rapid, noninvasive, and reproducible way of studying BAT activity thus providing a platform to advance research in this emerging field of human BAT.
An 89-year-old man was diagnosed with a submucosal tumor suspected to be a lipoma and was followed up for 6 years. The patient was admitted to the hospital because of increased tumor size and morphological changes despite negative bioptic findings. The lesion was diagnosed as an advanced adenocarcinoma of the ascending colon (cT3N0M0, cStage IIa). Laparoscopic-assisted right hemicolectomy with D3 lymph node dissection was performed. Pathological diagnosis of a surgically resected specimen revealed adenocarcinoma with lipohyperplasia (pT3N2aM0, pStage IIIb). Reports of colon cancer accompanied by colonic lipomas or lipohyperplasia are limited. This case showed an interesting submucosal tumor-like morphology because the cancer developed at the base of the lipohyperplasia and grew and spread below it.
Antibodies (Ab) specific for toxins of Clostridium difficile, opt. bound to a solid support, are new.  Esp. Ab are monospecific for either A or B toxin.  Also new are assays for toxigenic C. difficile using Ab. The immobilised Ab is incubated with the test sample to bind C. difficile antigens.  The bound antigen is then incubated with labelled, monospecific Ab, and the presence of label determined by detecting presence of the label.  Particularly, the label used is alkaline phosphatase.  In a modification, the monospecific Ab is not labelled, and detection is by reaction with a second, labelled antibody specific for the first. Alternatively, toxins are detected by agglutination of appropriately sensitised solid particles (or by inhibition of such agglutination).
Patients receive pomalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.