anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
In the Dose Escalation Phase of the study, we will identify the RPD2 of IM156. Subsequently, we will evaluate IM156 at the RP2D (established in the Dose Expansion Phase) and gemcitabine + nab-paclitaxel in the Dose Expansion Phase.
Patients will be treated with 0.9% sodium chloride (placebo) at Visit 1 and with iron carboxymaltose in 6 weeks at Visit 2. The patients will be blinded with respect to the treatment sequence.
Inhibition of S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice, but the underlying mechanisms are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory senescence-associated secretory phenotype (SASP). Cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology, but the specific role of S6K1 has not been determined. Here we show that S6K1 deletion does not reduce senescence but ameliorates inflammation in aged mouse livers. Using human and mouse models of senescence, we demonstrate that reduced inflammation is a liver-intrinsic effect associated with S6K deletion. Specifically, we show that S6K1 deletion results in reduced IRF3 activation; impaired production of cytokines, such as IL1β; and reduced immune infiltration. Using either liver-specific or myeloid-specific S6K knockout mice, we also demonstrate that reduced immune infiltration and clearance of senescent cells is a hepatocyte-intrinsic phenomenon. Overall, deletion of S6K reduces inflammation in the liver, suggesting that suppression of the inflammatory SASP by loss of S6K could underlie the beneficial effects of inhibiting this pathway on healthspan and lifespan.
BACKGROUND: The protective effectiveness provided by naturally acquired immunity against SARS-CoV-2 reinfection remain controversial.
OBJECTIVE: To systematically evaluate the protective effect of natural immunity against subsequent SARS-CoV-2 infection with different variants.
METHODS: We searched for related studies published in seven databases before March 5, 2023. Eligible studies included in the analysis reported the risk of subsequent infection for groups with or without a prior SARS-CoV-2 infection. The primary outcome was the overall pooled incidence rate ratio (IRR) of SARS-CoV-2 reinfection/infection between the two groups. We also focused on the protective effectiveness of natural immunity against reinfection/infection with different SARS-CoV-2 variants. We used a random-effects model to pool the data, and obtained the bias-adjusted results using the trim-and-fill method. Meta-regression and subgroup analyses were conducted to explore the sources of heterogeneity. Sensitivity analysis was performed by excluding included studies one by one to evaluate the stability of the results.
RESULTS: We identified 40 eligible articles including more than 20 million individuals without the history of SARS-CoV-2 vaccination. The bias-adjusted efficacy of naturally acquired antibodies against reinfection was estimated at 65% (pooled IRR = 0.35, 95% CI = 0.26-0.47), with higher efficacy against symptomatic COVID-19 cases (pooled IRR = 0.15, 95% CI = 0.08-0.26) than asymptomatic infection (pooled IRR = 0.40, 95% CI = 0.29-0.54). Meta-regression revealed that SARS-CoV-2 variant was a statistically significant effect modifier, which explaining 46.40% of the variation in IRRs. For different SARS-CoV-2 variant, the pooled IRRs for the Alpha (pooled IRR = 0.11, 95% CI = 0.06-0.19), Delta (pooled IRR = 0.19, 95% CI = 0.15-0.24) and Omicron (pooled IRR = 0.61, 95% CI = 0.42-0.87) variant were higher and higher. In other subgroup analyses, the pooled IRRs of SARS-CoV-2 infection were statistically various in different countries, publication year and the inclusion end time of population, with a significant difference (p = 0.02, p < 0.010 and p < 0.010), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. Despite the heterogeneity in included studies, sensitivity analyses showed stable results.
CONCLUSION: Previous SARS-CoV-2 infection provides protection against pre-omicron reinfection, but less against omicron. Ongoing viral mutation requires attention and prevention strategies, such as vaccine catch-up, in conjunction with multiple factors.
BACKGROUND: Major depressive disorder (MDD) is a prevalent mental health condition with significant societal impact. Owing to the intricate biological diversity of MDD, treatment efficacy remains limited. Immune biomarkers have emerged as potential predictors of treatment response, underscoring the interaction between the immune system and the brain. This study investigated the relationship between cytokine levels and cortical thickness in patients with MDD, focusing on the corticolimbic circuit, to elucidate the influence of neuroinflammation on structural brain changes and contribute to a deeper understanding of the pathophysiology of MDD.
METHOD: A total of 114 patients with MDD and 101 healthy controls (HC) matched for age, sex, and body mass index (BMI) were recruited. All participants were assessed for depression severity using the Hamilton Depression Rating Scale (HDRS), and 3.0 T T1 weighted brain MRI data were acquired. Additionally, cytokine levels were measured using a highly sensitive bead-based multiplex immunosorbent assay.
RESULTS: Patients diagnosed with MDD exhibited notably elevated levels of interleukin-6 (p = 0.005) and interleukin-8 (p = 0.005), alongside significant cortical thinning in the left anterior cingulate gyrus and left superior frontal gyrus, with these findings maintaining significance even after applying Bonferroni correction. Furthermore, increased interleukin-6 and interleukin-8 levels in patients with MDD are associated with alterations in the left frontomarginal gyrus and right anterior cingulate cortex (ACC).
CONCLUSIONS: This suggests a potential influence of neuroinflammation on right ACC function in MDD patients, warranting longitudinal research to explore interleukin-6 and interleukin-8 mediated neurotoxicity in MDD vulnerability and brain morphology changes.
An antibody binding to IPC was obtained by using an animal cell in which a cell membrane protein associatable with ILT7 was co-expressed as an immunogen. The antibody of the invention has a high specificity which allows immunological distinction between other ILT family molecules and ILT7. The anti-ILT7 antibody of the invention bound to IPC and inhibited the activity thereof. With the anti-ILT7 antibody of the invention, the IPC activity can be inhibited and an interferon-related disease can be treated or prevented. ILT7 expression is maintained even in IPC in the presence of IFN±. Therefore, an inhibitory action of IPC activity by the anti-ILT7 antibody can be expected even in an autoimmune disease patient with an increased production of IFN±.
The invention provides a disease prevention control facility layout method based on fairness. The problem is expressed as a two-layer decision structure with leader-follower characteristics, and a two-layer two-target non-linear integer programming model is constructed accordingly. The upper level is a dual target planning model with budget constraints, where the primary goal is to minimize the probability of the user being denied service and the secondary goal is to minimize the maximum latency. While the lower layer is a user competition balance model generated by the user's selection of a service facility, which determines the allocation pattern of user demand at the disease control facility. The invention adopts Genetic Algorithm (GA) with elite strategy to solve the upper layer problem, and adopts successive average method (MsA) to solve the lower layer problem. The development of software adopts free R language, and experiments show that the method can be used for disease prevention and control facility planning based on fairness and also can provide reference for budget planning.
INTRODUCTION: The survival benefit of axillary lymph node dissection (ALND), sentinel lymph node biopsy (SLNB) combined with radiation, and ALND combined with radiation remains unclear in breast cancer (BC) patients with 1-2 metastatic sentinel lymph nodes (SLNs). This study aims to rigorously evaluate the prognostic impact of these axillary evaluation modalities on BC patients with varying T-stages and to construct a survival prediction nomogram.
METHODS: Following screening for inclusion and exclusion criteria, data pertaining to BC patients were extracted from the SEER database. Overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Kaplan-Meier curves and Cox proportional hazards model among patients with different stages who underwent various axillary evaluation modalities. A nomogram was constructed to predict the probability of OS and BCSS.
RESULTS: A total of 20,283 patients were included, comprising 9626 who underwent breast-conserving surgery (BCS) and 10,657 who underwent mastectomy. In the T4 stage stratified analysis, both BCS and mastectomy groups exhibited superior OS and BCSS with ALND compared to SLNB combined with radiation. Further, ALND combined with radiation improved OS. However, for T1-3 stages, patients treated with ALND experienced similar or worse survival compared to those treated with SLNB combined with radiation. The calibration curve and C-index (0.746-0.794) of the nomogram demonstrated the efficacy of the survival prediction model.
CONCLUSION: In T1-3 BC patients with 1-2 metastatic SLNs, SLNB combined with radiation is a safe alternative to ALND. Conversely, for T4 patients, ALND combined with radiation may offer a preferable choice.
This study involves an investigational drug called pazopanib in combination with the chemotherapy drug vinorelbine. An investigational drug is a drug that has not been approved by the U.S. Food and Drug Administration (FDA) for use in the United States. Vinorelbine has been FDA approved to treat patients with NSCLC and breast cancer. Pazopanib is a vascular endothelial growth factor inhibitor, which means it may prevent the tumor from growing its own blood vessels thereby interfering with the growth of the tumor. Participants in this study will be assigned to one of three groups with each group receiving a higher dose of vinorelbine and pazopanib than the previous group. Vinorelbine will be given through a needle in the vein on days 1 and 8 of each 21 day study treatment cycle. Pazopanib is a pill which will be taken by mouth every day during the 21 day study treatment cycle.
In the electroacupuncture group, acupoints of Lieque (+), Chize (-), Sanyinjiao (-), Zusanli (+), Tanzhong (+) and Yutang (-) will be selected for electrical stimulation. Density wave will be selected, and the current intensity should be tolerated by the patients. Conventional anesthesia operation could be started after the connection of electroacupuncture, and acupuncture point stimulation was stopped 30min later.
PROBLEM TO BE SOLVED: To obtain the subject therapeutic medicine effective for the therapy of vertebra damages, especially traumatic vertebra damages, by including a specific compound (acid adduct) as an active ingredient. SOLUTION: This therapeutic medicine is obtained by mixing (A) a compound (acid adduct) of the formula (R<1> is H, OH) with (B), if necessary, a carrier such as gelatin, a saccharide or starch or a liquid carrier such as water, physiological salt solution or a sugar solution and subsequently preparing the mixture into the preparation suitable for the administration. When the mixture is prepared into capsules, gelatin, etc., is preferably used. The ingredient A is preferably contained in an amount of 0.01-80wt.% in the therapeutic agent. The administration method includes oral administration and parenteral administration. The therapeutic agent is administered at a daily dose of 0.01-20mg/kg on the parenteral administration and at a daily dose of 0.02-40mg/kg on the oral administration.
The investigators expect to recruit approximately 100 participants through the use of an IRB-approved survey and cover letter which will be distributed to anesthesiologists who have participated in a non-CME regional anesthesia workshop at VAPAHCS over the past 4 years. Prospective subjects will provide consent to participate by completing the requested survey. Subjects will not receive monetary remuneration for their participation. Selection for inclusion will not be based on gender, race, or socioeconomic status. There will be no recruitment of participants from vulnerable populations. Participants will receive a link to an online survey and if they prefer an alternate method, the investigators will send the participant the survey in Word document format or survey by telephone. The survey will ask for the number and types of nerve block procedures that the participant performed, nerve localization method (e.g., ultrasound, electrical stimulation, or both), and whether the nerve blocks performed were single-injection or catheter-based.
The working diagnosis Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA) is being increasingly recognized with the common use of high-sensitivity troponins and coronary angiography, accounting for 5% to 10% of all acute myocardial infarction presentations. Cardiac magnetic resonance (CMR) imaging is pivotal in patients presenting with suspected MINOCA, mainly to delineate those with a nonischemic cause, for example, myocarditis and Takotsubo syndrome, from those with true ischemic myocardial infarction, that is, MINOCA. The optimal timing for CMR imaging in patients with suspected MINOCA has been uncertain and, until recently, not been examined prospectively. Previous retrospective studies have indicated that the diagnostic yield decreases with time from the acute event. The SMINC studies (Stockholm Myocardial Infarction with Normal Coronaries) show that CMR should be performed early in all patients with the working diagnosis of MINOCA, with the possible exception of patients who are clearly identified as having Takotsubo syndrome as determined by echocardiography. In addition to CMR imaging, other investigations of importance in selected patients may be pulmonary artery computed tomography to exclude pulmonary embolism, optical coherence tomography to identify plaque disruption, and acetylcholine provocation to identify coronary artery spasm. Imaging of patients with the working diagnosis MINOCA, which is centered on CMR together with supplemental investigations, results in a clear diagnosis in approximately three-quarters of the patients. This is a good example of personalized medicine, because a correct diagnosis will not only increase the satisfaction of the individual patient but also result in optimizing treatment without harming the patient.
Our goal in this project is to conduct a randomized controlled trial of an evidence-based depression treatment intervention known as Measurement-Based Care (MBC), combined with brief Motivational Interviewing (MI) adherence counseling, in depressed people living with HIV/AIDS to assess its impact on ART adherence and clinical outcomes. MBC employs Depression Care Managers with expertise in depression management to screen for depression and help non-psychiatric physicians implement guideline-concordant, algorithm-driven antidepressant treatment. The Depression Care Manager use standardized metrics (depressive symptoms, side effects) and an algorithm to monitor treatment response and recommend changes. Weekly supervision from a psychiatrist ensures quality care. Biweekly contact between patients and the Depression Care Manager will include brief MI adherence counseling.

We will recruit 390 people living with HIV/AIDS on antiretroviral therapy (ART) with confirmed depression, and will conduct a randomized trial of the MBC intervention versus enhanced usual care. Our aims are: (1) to test whether MBC improves ART adherence and HIV clinical outcomes, (2) to assess the cost-effectiveness of MBC, and (3) to collect process measures concerning MBC implementation to inform replication at other sites. Since the Depression Care Manager role can be effectively filled by a behavioral health provider or nurse given appropriate training and supervision and the intervention has limited time requirements, this model is potentially replicable to a wide range of resource-constrained HIV treatment settings.
Patients will receive Burosumab monthly at visits 1,2 and 3 subcutaneously at a dose of 1.0 mg/kg. Dose may be adjusted as needed.
A package for holding a product has a structure with a hollow interior that defines a volume. The interior can store the product. The structure has an exterior side with an aperture. The package has a first member connected to the exterior side for selectively closing the aperture, opening the aperture and covering the aperture. The package has a second member connected to the structure for manipulating the structure. The product is applied to a user's skin through the aperture when the first member opens the aperture. The package is disposed so that the product is applied without the product contacting the user's hands.
The half-life of a Type I, II and III non-compartmentalized intracellular proteins is increased in living eukaryotic cells by contacting the cells with a regulator having an amino-terminal amino acid residue which is the same or similar to the amino-terminal residue of the intracellular protein. The regulator is a dipeptide, a small polypeptide or a carboxyl-terminal derivative of an amino acid. The dipeptide or small polypeptide has an N-terminal amino acid residue which is Arg, Lys or His for the Type I protein, Phe, Leu, Trp, Tyr or Ile for the Type II protein and Ala, Ser or Thr for the Type III protein. The carboxyl-terminal derivative of an amino acid may be an amino acid modified at its C-terminus by the addition of a group selected from methyl, ethyl, propyl, butyl and isobutyl. The amino acid modified is the N-terminal amino acid residue of the dipeptide or small polypeptide for the respective Type I, II and III proteins. Compositions may be formed containing the regulator for contacting with the cells. Increasing the half-life of intracellular protein with the regulator may be used for treating diseases resulting from an abnormal breakdown of a desired protein, and for enhancing in vivo production of a desired protein.
There is a paucity of literature analyzing the impact of fatigue from actual competitive soccer match-play on measures of neuromuscular function and muscle damage markers in youth players. Aims The main purpose was to analyze the acute pre- and post-competitive soccer match-play changes in measures of landing mechanics, stretch-shortening cycle capability, physical performance, muscle damage, and match intensity. A secondary purpose was to explore whether the players' maturity status and chronological age were associated with post-soccer match-play responses. Methods Thirty-two male youth outfield soccer players from two chronological competition age groups (U14 and U16) were assessed pre-and post-competitive soccer match-play for 2D dynamic knee valgus at landing (DKV), leg stiffness, reactive strength index, 20 m sprint time, CMJ-Abalakov jump height, creatine kinase and urea activity and visual analogue scale for muscle soreness (VAS). Players' maturity status was also estimated using a previously validated regression equation. Results There were statistically significant (p < 0.05) post-competitive soccer match-play impairments in all measures of stretch-shortening cycle capability and muscle damage markers assessed irrespective of the age group. Likewise, significant post-match play alterations in landing mechanics (DKV of the dominant leg) and physical performance (sprint time and jump height) scores were documented for the U14 players. Significant interactions between maturity and landing mechanics and VAS responses to competitive soccer match-play were also found whereby more mature players demonstrated larger post-match changes. Conclusion The findings of this study suggest the existence of a negative influence of competitive match-play on neuromuscular function and muscle damage in youth soccer.
To provide a health support device capable of effectively performing a diet program.SOLUTION: A health support device 100 comprises a reception section 111, a supporter information registration section 117, a matching processing section 113, and a notification section 114. The reception section 111 receives participation application information on participation of a dieter, who performs the diet program, in a diet program. The supporter information registration section 117 registers supporter information of a supporter. The supporter information registration section 117 further registers the dieter as a supporter in the supporter information when determining that the dieter can be registered in the supporter information on the basis of the participation application information. The matching processing section matches the participation application information with the supporter information. The notification section 114 notifies a user terminal of the dieter and a user terminal of the supporter of a matching result.SELECTED DRAWING: Figure 3
Hapten-carrier conjugates capable of eliciting anti hapten antibodies in vivo by administering, in a therapeutic composition, are disclosed. Anti-hapten antibodies elicited compete with free hapten upon subsequent challenge of a vaccinated individual. Methods of preparing the conjugates and therapeutic compositions are also disclosed. Where the hapten is a drug of abuse, a therapeutic composition containing the hapten-carrier conjugate is particularly useful in the treatment of drug addiction, more particularly, cocaine addiction. Passive immunization using antibodies raised against conjugates of the instant invention is also disclosed. The therapeutic composition is suitable for co-therapy with other conventional drugs.
Saline placebo will be initiated post fetal shoulder delivery (within 15 seconds). Oxytocin will be initiated immediately after placenta delivery (within 15 seconds).
OBJECTIVE: This study aims to explore how genetics evaluation and testing for patients with pediatric onset hearing loss affects their diagnosis and management.
METHODS: Retrospective chart review was completed for patients with pediatric hearing loss that were evaluated by a genetic counselor from 2008 to 2022 with data entry into a REDCap database. Descriptive statistical analysis was completed.
RESULTS: Four hundred twenty-nine patients with pediatric onset hearing loss were evaluated by genetics. Majority of patients presented with bilateral (67 %) and sensorineural (83 %) hearing loss. Genetic testing was recommended for 76 % of patients with pediatric hearing loss evaluated by a genetic counselor with 70 % completing some or all recommended tests. Overall genetic testing diagnostic rate was 34 %, with 41 % of diagnoses syndromic. Yearly trends noted an increasing number of patients evaluated, tests ordered, and subsequently an increased number of diagnoses overtime. For diagnostic results, management recommendations were made for 45 % of patients (35/78) and for 92 % of family members (72/78). This compared to total management recommendations for all patients (82/429, 19 %) and family members (110/429, 26 %).
CONCLUSION: This study identified a genetic testing diagnostic rate for pediatric hearing loss of 34 % over 14 years. This study notes the beneficial outcomes of patients with hearing loss and their families meeting with a genetic counselor and the importance of collaboration with hearing loss management colleagues. It highlights the value a genetic counselor consult can add to a patient's diagnostic journey, in addition to how genetic testing impacts management for patients and their families.