anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This study is a single arm, open label, multicenter Phase Ib/II study aimed at evaluating the safety and efficacy of first-line treatment of patients with marginal zone lymphoma with combination therapy of Linperlisib and obinutuzumab. The study is divided into Phase Ib safety introduction stage, and Phase II is recommended; As well as the Phase II expansion phase, the research design is shown in the following figure. Phase Ib is the safety introduction period, with the main purpose of determining the recommended Phase II effective dose (RP2D) based on dose limiting toxicity (DLT). Six subjects are planned to be enrolled to observe the safety of one cycle of combination therapy with Linperlisib (80 mg, once daily). If\<2 cases of DLT occur, the RP2D of Linperlisib will be 80 mg, once daily; If there are ≥ 2 cases of DLT, RP2D is 60 mg once daily. Phase II is the expansion phase, which involves induction therapy with two cycles of Linperlisib RP2D combined with obinutuzumab. All patients who achieve complete remission (CR) or partial remission (PR) after induction therapy receive induction therapy with a dose of Linperlisib, which is maintained every 28 days for one cycle until disease progression or other reasons lead to discontinuation. During the maintenance phase, the use of Linperlisib should not exceed 24 months. If the disease is stable (SD) or (PD), the patient will be removed from the group. If a patient fails to achieve CP or PR after two cycles of induction therapy, the researcher will determine whether to continue induction therapy. Induction therapy can last up to six cycles.The aim is to evaluate the efficacy and safety of first-line treatment with Linperlisib combined with obinutuzumab in patients with marginal zone lymphoma (MZL).
A computer implemented method and system is for training a subject's articulation. The system will receive, access and analyze the speech audio and video data of the subject. The data will be compared to standard speech audio and video data to calculate the deviation of the articulatory parameters between the recorded data of the subject and the standard data. The system will then deconstruct the speech unit and separately play the standard tongue movements, lip movements, jaw movements, and airstream generation. The system will then enable a gradual time converging of the initial separately played standard tongue movements, jaw movements, lip movements and airstream generation in response to a magnitude of the at least articulatory parameter deviation decreasing. Similarly, the system will adapt the display speed and the number of repetitions of these movements to optimize the articulation training.
Hypotension, including postural hypotension, has been observed during therapy with tranylcypromine sulfate tablets. At doses above 30 mg daily, postural hypotension is a major adverse reaction and may result in syncope. Symptoms of postural hypotension are seen most commonly, but not exclusively, in patients with pre-existing hypertension. Blood pressure usually returns rapidly to pretreatment levels upon discontinuation of tranylcypromine sulfate tablets.  
  
Dosage increases should be made more gradually in patients with a tendency toward hypotension and/or postural hypotension (e.g., elderly patients) [see Dosage and Administration (2.2) and Use in Specific Populations (8.5)].Such patients should be closely observed for postural changes in blood pressure throughout treatment. Also, when tranylcypromine sulfate tablets are used concomitantly with other agents known to cause hypotension, the possibility of additive hypotensive effects should be considered [see Drug Interactions (7.1)].Postural hypotension may be relieved by having patients lie down until blood pressure returns to normal.
Oral 18 mg doses of LY2216684 on days 1-6 with a single oral 1 mg dose of lorazepam on day 3 in treatment period 1. Oral doses of placebo on days 1-6 with a single oral 1 mg dose of lorazepam on day 3 in treatment period 2. There is a washout period of at least 7 days between dosing periods.
BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period.
METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation.
RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes.
CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis.
IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.
BACKGROUND: Apolipoprotein B mRNA editing catalytic polypeptide (APOBEC), an endogenous mutator, induces DNA damage and activates the ataxia telangiectasia and Rad3-related (ATR)-checkpoint kinase 1 (Chk1) pathway. Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer (MIBC), it has a poor survival rate. Therefore, this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B (APOBEC3B) expressing MIBC.
METHODS: Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC. The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis. Western blot analysis was performed to confirm differences in phosphorylated Chk1 (pChk1) expression according to the APOBEC3B expression. Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.
CONCLUSION: There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC. Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels. Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression. Compared to cisplatin single treatment, combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression. Conclusion: Our study shows that APOBEC3B's higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition. This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.
To accept the toxic side effects of any treatment, whether medical, surgical or radiotherapeutic, cannot be avoided but implies to evaluate them taking into account the severity and prognosis of the disease that is concerned. Screening, preventing and treatment of these side effects are an integral aspect of the treatment of cancers. We will here review the contribution of the cardio-oncology, a recently emerged medical specialty. Cardiac irradiation cannot be avoided when treating several cancers, most frequently left sided breast cancer. As soon as radiotherapy is considered, it is of prime importance to evaluate each patient's risk factors and to handle them. If technical progresses have led to the complete disappearance of acute side effects of radiotherapy, this is not true for the delayed ones that may occur many years after the irradiation. Hence the need for «red flags» and for a systematic follow-up. Cardiac complications of left breast irradiation concern all aspects of cardiology: diseases of cardiac rhythm, valvulopathies, heart failure, coronary and pericardial disorders.
The GetActive program uses a multimodal approach to introduce and reinforce new skills, including didactics, in-session activities, discussions, and weekly practice assignments (homework). The GetActive sessions reflect a purposeful integration of the three treatment approaches (relaxation methods, stress appraisal \& coping, and growth enhancement). The format is a 10-week program with weekly meetings and a focus on relaxation response strategies, cognitive behavioral training, positive psychology and mind-body interactions.
This invention relates to a novel herbal composition comprising an extract of flowering and fruiting heads of the plant,  Sphaeranthus indicus . The said extract of  Sphaeranthus indicus  contains a compound, 3a-hydroxy-5a,9-dimethyl-3-methylene-3a,4,5,5a,6,7,8,9b-octahydro-3H-naphtho[1,2-b]furan-2-one (7-Hydroxy-4,11(13)-eudesmadien-12,6-olide) (compound 1), as a bioactive marker. The invention also relates to a composition comprising 3a-hydroxy-5a,9-dimethyl-3-methylene-3a,4,5,5a,6,7,8,9b-octahydro-3H-naphtho[1,2-b]furan-2-one (compound 1) as an active ingredient. The invention also relates to methods of manufacture of the said compositions. The invention also relates to methods of administration of the said compositions to a subject in need of treatment for an inflammatory disorder. The invention also relates to tumor necrosis factor-  (TNF-α) and interleukin (IL-1, IL-6, IL-8) inhibitory activity of the said compositions. The invention relates to inhibition of the expression of intercellular adhesion molecule 1 (ICAM-1), vascular-cell adhesion molecule 1 (VCAM-1), and E-Selectin by the said compositions. The said compositions may optionally contain at least one anti-inflammatory agent or can be used in combination with at least one anti-inflammatory agent.
Bing-Neel syndrome (BNS) is a very rare manifestation of Waldenström macroglobulinaemia (WM), in which lymphoplasmacytic cells invade the central nervous system. The clinical presentation includes symptoms of headaches, visual floaters, neuropathy, seizures and gait abnormalities. Here, we describe an elderly woman, who presented with complaints of visual floaters, progressive neuropathy and cognitive changes. Workup including a bone marrow biopsy confirmed the diagnosis of WM. Shortly afterwards, the patient experienced a seizure leading to hospitalisation, which revealed a right frontal lobe lesion on brain MRI. A biopsy of the lesion showed a small B cell lymphoma positive for an MYD88 mutation, confirming BNS. The patient was initially treated with ibrutinib, before transitioning to zanubrutinib. However, she developed disease progression necessitating radiotherapy with lenalidomide and rituximab maintenance therapy, which achieved remission. This case sheds light on the diagnosis and management of a very rare complication of a rare disease.
CSE is a widely used technique to provide analgesia in laboring patients. One of the disadvantages of the CSE is the delay in recognizing the mal-position of the epidural catheter, which is initially masked due to the effects of the spinal component. A mal-positioned epidural catheter can cause unnecessary maternal discomfort and dissatisfaction, as it requires a repeat procedure when the effect of spinal drug wears off. Additionally, in the event of emergency caesarean delivery, it would be advantageous to know that the catheter is properly placed. Low current electrical stimulation test, or the Tsui test, has been used successfully to confirm catheter location in the epidural space. Our objective in this study is to test the usefulness of the Tsui test to confirm the correct placement of the epidural catheter during CSE in laboring patients.

Two groups of patients will be studied. In the first group, after the placement of the epidural catheter and noting the electric current required to elicit a motor response (maximum current used is 20 mA), a spinal needle is introduced one inter vertebral space below the space where the epidural catheter is inserted and 0.7 ml of 0.25% isobaric bupivacaine and 15 mcg of fentanyl is injected intrathecally. The epidural catheter is then re-stimulated and the magnitude of the current required to reproduce the motor response is noted. The stimulation is repeated after 5, 10, and 15 minutes. The second group consists of patients with accidental dural puncture. An intrathecal catheter is inserted and the Tsui test performed (maximum current used is 2 mA), followed by the injection of same mixture of local anesthetic and opioid as used in the first group. The Tsui test is repeated at 5, 10 and 15 minute intervals, similar to what is done in the epidural group. After 15 minutes, patients in both groups are managed as per departmental policy. In both the groups, the Tsui test will be repeated after 120 minutes during the maintenance of labor analgesia to determine the change in intensity of current required to elicit the motor response.
Most malignant tumors causing bile duct obstruction, such as pancreatic adenocarcinoma, gallbladder carcinoma or cholangiocarcinoma, have an extremely poor prognosis. At the time of diagnosis the majority of these tumors will be unresectable with a median survival of 4-6 months. Palliation is the goal for those patients with unresectable tumors and limited survival and for those at high risk for attempts at curative resection.

Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic stent insertion is considered the method of choice for palliative treatment of malignant bile duct obstruction (MBDO). However, it can cause complications, such as pancreatitis, bleeding, perforation, cholangitis and stent migration in a significant proportion of treated patients. Clogging of plastic stents is a predictable consequence and requires periodic stent exchanges with attendant risks and costs. While endoscopic stenting is clearly indicated for relief of cholangitis or refractory pruritus, the role of stenting in patients with jaundice alone, abdominal pain, or failure to thrive due to malignancy is less clear. Given the risk for complications and costs, endoscopic therapy might be justified in these clinical scenarios if quality of life (QOL) is significantly improved. A few available studies have demonstrated improved QOL in stented patients. However, these studies include a small number of patients and/or are retrospective in design. Therefore, more evidence to support routine palliative biliary drainage in patients with MBDO is desired.
Tolfenpyrad, a highly effective and broad-spectrum insecticide and acaricide extensively utilized in agriculture, presents a potential hazard to nontarget organisms. This study was designed to explore the toxic mechanisms of tolfenpyrad on zebrafish embryos. Between 24 and 96 h after exposure of the fertilized embryos to tolfenpyrad at concentrations ranging from 0.001 to 0.016 mg/L (96 h-LC50 = 0.017 mg/L), lethal effects were apparent, accompanied with notable anomalies including pericardial edema, increased pericardial area, diminished heart rate, and an elongated distance between the venous sinus and the arterial bulb. Tolfenpyrad elicited noteworthy alterations in the expression of genes pertinent to cardiac development and apoptosis, with the most pronounced changes observed in the cardiac development-related genes of bone morphogenetic protein 2b (bmp2b) and p53 upregulated modulator of apoptosis (puma). The findings underscore that tolfenpyrad induces severe cardiac toxicity and mitochondrial damage in zebrafish embryos. This data is imperative for a comprehensive assessment of tolfenpyrad risks to aquatic ecosystems, particularly considering the limited knowledge regarding its detrimental impact on aquatic vertebrates.
This is a phase II study of gemcitabine and Herceptin given weekly as a bolus infusion administered concurrently with radiotherapy in patients with regionally confined resectable or unresectable adenocarcinoma of the pancreas that overexpress HER2. Patients will be treated with external beam radiation in a standard manner over 6 weeks prior to surgical exploration. Gemcitabine and Herceptin will be administered on the first day of irradiation and weekly during the course of radiotherapy. Patients will be assessed for resectability after treatment and may undergo a pancreatic resection. Patients will then be treated with once weekly gemcitabine and herceptin for three weeks followed by 1 week of rest for up to 6 months. Patients will be assessed clinically for toxicity, tumor response, progression-free survival, and overall survival.
The population with metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common worldwide. Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care. Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD, but it has associated risks and limitations. This has spurred the exploration of non-invasive diagnostics for MAFLD, especially for steatohepatitis and fibrosis. These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements, serum tests, imaging or stool metagenome profiling. However, they still need rigorous and widespread clinical validation for the diagnostic performance.
BACKGROUND: Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene CACNA1C. Initially, Timothy syndrome was characterized by a cardiac presentation of long QT syndrome and syndactyly of the fingers and/or toes, all associated with the CACNA1C variant, Gly406Arg. However, subsequent identification of diverse variants in CACNA1C has expanded the clinical spectrum, revealing various cardiac and extra-cardiac manifestations. It remains underexplored whether individuals with the canonical Gly406Arg variants in mutually exclusive exon 8A (Timothy syndrome 1) or exon 8 (Timothy syndrome 2) exhibit overlapping symptoms. Moreover, case reports have indicated that some CACNA1C variants may produce a cardiac-selective form of Timothy syndrome often referred to as non-syndromic long QT type 8 or cardiac-only Timothy syndrome, however few reports follow up on these patients to confirm the cardiac selectivity of the phenotype over time.
METHODS: A survey was administered to the parents of patients with Timothy syndrome, querying a broad range of symptoms and clinical features. Study participants were organized into 5 separate categories based on genotype and initial diagnosis, enabling comparison between groups of patients which have been described differentially in the literature.
RESULTS: Our findings reveal that Timothy syndrome patients commonly exhibit both cardiac and extra-cardiac features, with long QT syndrome, neurodevelopmental impairments, hypoglycemia, and respiratory issues being frequently reported. Notably, the incidence of these features was similar across all patient categories, including those diagnosed with non-syndromic long QT type 8, suggesting that the 'non-syndromic' classification may be incomplete.
CONCLUSIONS: This study represents the first Natural History Study of Timothy syndrome, offering a comprehensive overview of the disease's clinical manifestations. We demonstrate that both cardiac and extra-cardiac features are prevalent across all patient groups, underscoring the syndromic nature of CACNA1C variants. While the critical role of long QT syndrome and cardiac arrhythmias in Timothy syndrome has been well recognized, our findings indicate that hypoglycemia and respiratory dysfunction also pose significant life-threatening risks, emphasizing the need for comprehensive therapeutic management of affected individuals.
BACKGROUND: Juxtarenal aortic occlusion (JRAO), in which the occlusion of the aorta extends to just below the renal artery, is often treated by bypass surgery because of concerns about the risk of procedural failure and fatal embolization to abdominal organs when treated with endovascular treatment (EVT). This study assessed the outcome of EVT for JRAO compared with aorto-biiliac /aorto-bifemoral (AOB) or axillo-bifemoral (AXB) bypass.
METHODS: A retrospective review of an international database created by 30 centers in Asia (CHronic Abdominal Aortic Occlusion, ASian Multicenter registry) was performed for patients who underwent revascularization for chronic total occlusion of the infrarenal aorta from 2007 to 2017. Of the 436 patients, 130 with JRAO (Forty-seven AOBs, 32 AXBs, and 51 EVTs) from 25 institutions were included in this study.
RESULTS: Patients were significantly older in the AXB and EVT groups and more malnourished in the EVT group than the AOB group. EVT was attempted but failed in 1 patient. Seven patients (1 [2.1%] in the AOB group, 1 [3.1%] in the AXB group, and 5 [9.8%] in the EVT group) died during hospitalization, but most of the causes in the EVT group were not related to the revascularization procedure. No visceral embolism was observed, which had been concerned, even though protection was performed only in 2 cases of the EVT group. At the latest follow-up (median duration 3.0 years), the ankle-brachial pressure index was significantly higher in the order of AOB, EVT, and AXB. At 4 years, the estimated primary and secondary patency rates of the AOB group (87.5% and 90.3%, respectively) were significantly higher than the AXB group (66.7% and 68.6%, respectively).
CONCLUSIONS: AOB remains the gold standard and should be the first choice for acceptable risk patients. For frail patients, EVT is a good option and likely preferable as a first-line treatment compared to AXB.
FIELD: medicine, pharmacy. SUBSTANCE: invention relates to pharmaceutical agents used for treatment of patients with severe acute and chronic damages resulting to blood loss or depletion of its functional properties and accompanying immunodeficiency state. Plasma substitute solution has isotonic solution and DNA sodium salt additionally obtained from animal raw with mean molecular mass (1.5-550) x 10 3  Da and hyperchromic effect 28-46% taken in the amount 5 x 10 -5  g/1 l of isotonic solution. Except for the basic curative effect this agent stimulates hemopoiesis and myelopoiesis being without adverse effects. EFFECT: increase percent of viability, decreased time of patients treatment. 5 tbl, 1 ex