anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The efficacy of RYBREVANT was evaluated in PAPILLON (NCT04538664), in a randomized, open-label, multicenter study. Eligible patients were required to have previously untreated locally advanced or metastatic NSCLC with EGFR Exon 20 insertion mutations measurable disease per RECIST v1.1, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1, and adequate organ and bone marrow function. Patients with brain metastases at screening were eligible for participation once they were definitively treated, clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization. Patients with a medical history of interstitial lung disease or active ILD were excluded from the clinical study.

A total of 308 patients were randomized 1:1 to receive RYBREVANT in combination with carboplatin and pemetrexed (n=153) or carboplatin and pemetrexed (n=155). Patients received RYBREVANT intravenously at 1,400 mg (for patients < 80 kg) or 1,750 mg (for patients ≥ 80 kg) once weekly through 4 weeks, then every 3 weeks with a dose of 1,750 mg (for patients < 80 kg) or 2,100 mg (for patients ≥ 80 kg) starting at Week 7 until disease progression or unacceptable toxicity. Carboplatin was administered intravenously at area under the concentration-time curve 5 mg/mL per minute (AUC 5) once every 3 weeks, for up to 12 weeks. Pemetrexed was administered intravenously at 500 mg/m 2 on once every 3 weeks until disease progression or unacceptable toxicity. Patients were stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1) and prior brain metastases (yes or no). 

The primary efficacy outcome measure was progression-free survival (PFS) as assessed by blinded independent central review (BICR). Additional efficacy outcome measures included overall response rate (ORR), duration of response (DOR) and overall survival (OS). Cross-over to single agent RYBREVANT was permitted for patients who had confirmed disease progression on carboplatin and pemetrexed.

The median age was 62 (range: 27 to 92) years, with 40% of the patients ≥ 65 years of age; 58% were female; 61% were Asian and 36% were White, 0.7% were Black or African American and race was not reported in 2.3% of patients; 93% were not Hispanic or Latino. Baseline ECOG performance status was 0 (35%) or 1 (65%); 58% were never smokers; 23% had history of brain metastasis and 84% had Stage IV cancer at initial diagnosis.

PAPILLON demonstrated a statistically significant improvement in progression free survival for patients randomized to RYBREVANT in combination with carboplatin and pemetrexed compared with carboplatin and pemetrexed.

Efficacy results are summarized in Table 21 and Figure 3.

Figure 3: Kaplan-Meier Curve of PFS in Previously Untreated NSCLC Patients by BICR Assessment – Papillon Study

While OS results were immature at the current analysis, with 44% of pre-specified deaths for the final analysis reported, no trend towards a detriment was observed. Seventy-five (48%) of the treated patients crossed over from the carboplatin and pemetrexed arm after confirmation of disease progression to receive RYBREVANT as a single agent.
In the postmarketing experience with SOMA, cases of dependence, withdrawal, and abuse have been reported with prolonged use. Most cases of dependence, withdrawal, and abuse occurred in patients who have had a history of addiction or who used SOMA in combination with other drugs with abuse potential. However, there have been post-marketing adverse event reports of SOMA-associated abuse when used without other drugs with abuse potential. Withdrawal symptoms have been reported following abrupt cessation after prolonged use. To reduce the chance of SOMA dependence, withdrawal, or abuse, SOMA should be used with caution in addiction-prone patients and in patients taking other CNS depressants including alcohol, and SOMA should not be used more than two to three weeks for the relief of acute musculoskeletal discomfort.

SOMA, and one of its metabolites, meprobamate (a controlled substance), may cause dependence [see Clinical Pharmacology (12.3)].
BACKGROUND: Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing glycerophosphodiesterase, EDI3 and reported its association with metastasis-free survival in endometrial cancer. We also observed that silencing EDI3 slowed cell migration and other cancer-relevant phenotypes in vitro. Recent work demonstrated high EDI3 expression in ER-HER2+ breast cancer compared to the other molecular subtypes. Silencing EDI3 in ER-HER2+ cells significantly reduced cell survival in vitro and decreased tumor growth in vivo. However, a role for EDI3 in tumor metastasis in this breast cancer subtype was not explored. Therefore, in the present work we investigate whether silencing EDI3 in ER-HER2+ breast cancer cell lines alters phenotypes linked to metastasis in vitro, and metastasis formation in vivo using mouse models of experimental metastasis.
METHODS: To inducibly silence EDI3, luciferase-expressing HCC1954 cells were transduced with lentiviral particles containing shRNA oligos targeting EDI3 under the control of doxycycline. The effect on cell migration, adhesion, colony formation and anoikis was determined in vitro, and significant findings were confirmed in a second ER-HER2+ cell line, SUM190PT. Doxycycline-induced HCC1954-luc shEDI3 cells were injected into the tail vein or peritoneum of immunodeficient mice to generate lung and peritoneal metastases, respectively and monitored using non-invasive bioluminescence imaging. Metabolite levels in cells and tumor tissue were analyzed using targeted mass spectrometry and MALDI mass spectrometry imaging (MALDI-MSI), respectively.
RESULTS: Inducibly silencing EDI3 reduced cell adhesion and colony formation, as well as increased susceptibility to anoikis in HCC1954-luc cells, which was confirmed in SUM190PT cells. No influence on cell migration was observed. Reduced luminescence was seen in lungs and peritoneum of mice injected with cells expressing less EDI3 after tail vein and intraperitoneal injection, respectively, indicative of reduced metastasis. Importantly, mice injected with EDI3-silenced cells survived longer. Closer analysis of the peritoneal organs revealed that silencing EDI3 had no effect on metastatic organotropism but instead reduced metastatic burden. Finally, metabolic analyses revealed significant changes in choline and glycerophospholipid metabolites in cells and in pancreatic metastases in vivo.
CONCLUSIONS: Reduced metastasis upon silencing supports EDI3's potential as a treatment target in metastasizing ER-HER2+ breast cancer.
AIMS: Neutrophil extracellular trap (NET), which is formed by DNA threads, induces septic shock by aggravating systemic inflammation. An intravenous administration of deoxyribonuclease is regarded as a compelling modality for treating septic shock. However, alternative routes should be chosen when cutaneous veins are all collapsed due to hypotension. In this study, we genetically engineered this enzyme to develop a rectal suppository formulation to treat septic shock.
MAIN METHODS: Dnase1 was mutated at two amino acid residues to increase its stability in the blood and fused with a cell-penetrating peptide CR8 to increase its absorption through the rectal mucosa, which is designated AR-CR8. The life-saving effect of AR-CR8 was evaluated in a LPS-induced shock mouse model.
KEY FINDINGS: AR-CR8 was shown to remove NETs effectively in human neutrophils. When AR-CR8 was administered to the mouse rectum, the deoxyribonuclease activity in the mouse serum was significantly increased. In the LPS-induced shock model, 90 % of the control mice died over 72 h after LPS injection. In contrast, the rectal administration of AR-CR8 showed a mortality rate of 30 % by 72 h after LPS injection. The Log-rank test revealed that the survival rate is significantly higher in the AR-CR8 group. The NET markers in the mouse serum were enhanced by LPS, and significantly downregulated in the AR-CR8 group. These results suggest that AR-CR8 ameliorates LPS-induced shock by degrading NETs.
SIGNIFICANCE: The engineered DNASE1 could be developed as a rectal suppository formulation to treat septic shock urgently at out-of-hospital places where no syringe is available.
The investigators prospectively will survey adult female patients with functional gastroenterological symptoms according to the Rome III criteria, and a suspected diagnosis of NCWS. The patients will be recruited between January 2017 and January 2018 at the same 2 centers. Most of the patients will be referred owing to gastrointestinal and extraintestinal symptoms, the onset of which, they reported, could be related to wheat ingestion. In addition, patients will be asked about the presence and characteristics of gynaecological disorders using an ad hoc questionnaire. All the patients will be evaluated at baseline (i.e. at diagnosis) and after at least a 6-months period of gluten-free diet.
This pilot study will use a mixed-methods design called an exploratory sequential translational research design. In this type of study design, the initial qualitative phase informs the design of an intervention (in this case a TB infection ECHO) and an instrument (in this case structured surveys) to study the intervention. The third phase implements the designed intervention and/or instrument to collect data and quantitatively assess the outcomes of interest (in this case feasibility and impact). The final aspect of the third phase explores an EMR data query to assess the reach of the intervention (providers' testing and treatment in the real world). In Aim 1, 25 primary care team members from our Brown Family Medicine, Care New England, and federally qualified health center networks will be purposively sampled to undergo key informant interviews regarding LTBI testing and treatment knowledge, attitudinal, and skill gaps. Questions will be asked to ascertain gaps throughout the entire latent TB infection care cascade. The results from Aim 1 will be used to design the survey instrument and the curriculum for an innovative, telementoring program (TB infection ECHO). In Aim 2, 12 primary care team members will be recruited to participate in a virtual six-month TB infection ECHO course. Participants will be asked to complete quantitative surveys before and after the course as well as post-session surveys following each session. Survey questions will assess feasibility measures related to process, resources, and management and impact measures related to learning and performance. Paired data from pre- and post-course surveys will be analyzed accordingly depending on the distribution of results. In Aim 3, data will be extracted from two ECHO participants' clinic sites before, during, and after ECHO implementation. Data will include information about LTBI testing and treatment to understand the reach and impact of the intervention of providers' testing and treatment behavior. This study will lead to an ECHO research framework that can be used for future ECHO courses that address other diseases in Rhode Island (RI).
Patients were seated in the isokinetic dynamometer with their hips flexed to 85º. A target sine wave with a maximum amplitude of 30% MVIC and a minimum amplitude of 5% MVIC and a frequency of 0.128 Hz was visually presented to the patient.31 The patient was instructed to match their torque to the presented target throughout the duration of testing. Each visuomotor therapy trial was 60-seconds, followed by 30-seconds of rest for 10 repetitions, totaling 15 minutes.
Within 6 to 24 hours prior to vaccination, patients undergo vaccination skin site preparation in the opposite inguinal region with tetanus toxoid. Patients then receive 111 In-labeled CMV-DC.
BACKGROUND: Though robotic adoption for eTEP surgery has decreased technical barriers to minimally invasive repairs of large ventral hernias, relatively few studies have examined outcomes of robotic-specific eTEP surgery. This study evaluates safety, feasibility, and early outcomes of ERAS/same-day discharge protocols for robotic eTEP ventral hernia repairs.
METHODS: A retrospective chart review was performed for all robotic eTEP hernia surgeries at a single institution between 2019 and 2022. Analysis included patient demographics, hernia characteristics, intraoperative data, and post-operative outcomes at 30 days. ERAS protocol included: judicious use of urinary catheters with removal at end of case if placed, bilateral transversus abdominus plane (TAP) blocks, post-operative abdominal wall binder, and opioid-sparing perioperative analgesia. Patients were discharged same day from post-anesthesia care unit (PACU) if they lacked comorbidities requiring observation post-anesthesia and demonstrated stable vital signs, adequate pain control, ability to void, and ability to ambulate. Hospital length of stay (LOS) was considered 0 for same-day PACU discharges or hospitalizations < 24 h.
RESULTS: 102 patients were included in this case series. 69% (70/102) of patients were discharged same-day (mean LOS 0.47 ± 0.80 days). Within 30 post-operative days, 3% (3/102) of patients presented to the ER, 2% (2/102) were readmitted to the hospital, and 1% (1/102) required reoperation. There was 1 serious complication (Clavien-Dindo grade 3/4) with an aggregate complication rate of 7.8%.
CONCLUSIONS: Our initial experience with ERAS protocols and same-day discharges after robotic eTEP repair demonstrates this approach is safe and feasible with acceptable short-term patient outcomes. Compared to traditional open surgery for large ventral hernias, robotic eTEP may enable significant reductions in hospital LOS as adoption increases.
Inflammatory skin diseases include a series of disorders characterized by a strong activation of the innate and adaptive immune system in which proinflammatory cytokines play a fundamental role in supporting inflammation. Skin inflammation is a complex process influenced by various factors, including genetic and environmental factors, characterized by the dysfunction of both immune and non-immune cells. Psoriasis (PS) and atopic dermatitis (AD) are the most common chronic inflammatory conditions of the skin whose pathogeneses are very complex and multifactorial. Both diseases are characterized by an immunological dysfunction involving a predominance of Th1 and Th17 cells in PS and of Th2 cells in AD. Suppressor of cytokine signaling (SOCS) proteins are intracellular proteins that control inflammatory responses by regulating various signaling pathways activated by proinflammatory cytokines. SOCS signaling is involved in the regulation and progression of inflammatory responses in skin-resident and non-resident immune cells, and recent data suggest that these negative modulators are dysregulated in inflammatory skin diseases such as PS and AD. This review focuses on the current understanding about the role of SOCS proteins in modulating the activity of inflammatory mediators implicated in the pathogenesis of inflammatory skin diseases such as PS and AD.
PURPOSE: To obtain a composition for dyeing bacterial plaque capable of visibly detecting bacterial plaque, by solubilizing a bacterial plaque-dyeing coloring matter in the liquid crystal phase of an aqueous surfactant solution to raise the selective dyeing ability of the coloring matter on bacterial plaque. CONSTITUTION: An aqueous surfactant solution is prepared at such concentrations that the surfactant form a liquid crystal phase and then incorporated with a bacterial plaque-dyeing coloring matter, esp. a tar-based xanthene coloring matter for use in foods, cosmetics and medicines to effect solubilizing (encapsulating) the coloring matter in the liquid crystal phase of the aqueous solution. The contents of the coloring matter and the surfactant in the aqueous solution are 0.02-5wt.% and 3-70wt.%, respectively. This aqueous solution is prepared, by a conventional means, into a dyeing liquid, gel, tablets, bacterial plaque agent, etc.  By dyeing bacterial plaque with this coloring matter, the plaque can be easily observed with the naked eye and the dyeing speed on the plaque selectively accelerated; thus, this composition (aqueous solution) can be used as a means for detecting bacterial plaque for the purpose of efficiently removing it.
In this arm of the study, caregivers will receive usual care and an automated brief text message referral to the Feed1st program from the health care provider. The text message referral will align as closely as possible with the face-to-face referral.
INTRODUCTION: Pediatric digestive volvulus is a serious condition that carries with it a high rate of morbidity and mortality.
OBJECTIVE: This review highlights the pearls and pitfalls of pediatric digestive volvulus, including the presentation, diagnosis, and management in the emergency department (ED) based on current evidence.
DISCUSSION: Pediatric digestive volvulus is a deadly condition most commonly associated with malrotation. It occurs when the stomach or small intestine twists on itself, resulting in ischemia and potentially strangulation with necrosis and perforation. Presentation differs based on the gastrointestinal (GI) segment affected, degree of twisting, and acuity of the volvulus. Gastric volvulus most commonly presents with retching with or without nonbilious emesis and epigastric distension with pain, while midgut volvulus typically presents with bilious emesis in infants. Patients with GI necrosis and perforation may present with hemodynamic compromise and peritonitis. If suspected, emergent consultation with the pediatric surgery specialist is necessary, and if this is not available, transfer to a center with a pediatric surgeon is recommended. Imaging includes plain radiography, ultrasound, or upper GI series, while treatment includes resuscitation, administration of antibiotics, and emergent surgical decompression and detorsion of the involved segments.
CONCLUSION: An understanding of pediatric digestive volvulus and its many potential mimics can assist emergency clinicians in diagnosing and managing this deadly disease.
### “Sleep-Driving” and Other Complex Behaviors

There have been reports of people getting out of bed after taking a sedative-hypnotic and driving their cars while not fully awake, often with no memory of the event. If a patient experiences such an episode, it should be reported to his or her doctor immediately, since “sleep-driving” can be dangerous. This behavior is more likely to occur when temazepam is taken with alcohol or other central nervous system depressants (see ). Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events. WARNINGS
BACKGROUND: Estetrol (E4) is a natural estrogen produced by the fetal liver during pregnancy. Due to its favorable safety profile, E4 was recently approved as estrogenic component of a new combined oral contraceptive. E4 is a selective ligand of estrogen receptor (ER)α and ERβ, but its binding to the G Protein-Coupled Estrogen Receptor (GPER) has not been described to date. Therefore, we aimed to explore E4 action in GPER-positive Triple-Negative Breast Cancer (TNBC) cells.
METHODS: The potential interaction between E4 and GPER was investigated by molecular modeling and binding assays. The whole transcriptomic modulation triggered by E4 in TNBC cells via GPER was explored through high-throughput RNA sequencing analyses. Gene and protein expression evaluations as well as migration and invasion assays allowed us to explore the involvement of the GPER-mediated induction of the plasminogen activator inhibitor type 2 (SERPINB2) in the biological responses triggered by E4 in TNBC cells. Furthermore, bioinformatics analysis was aimed at recognizing the biological significance of SERPINB2 in ER-negative breast cancer patients.
RESULTS: After the molecular characterization of the E4 binding capacity to GPER, RNA-seq analysis revealed that the plasminogen activator inhibitor type 2 (SERPINB2) is one of the most up-regulated genes by E4 in a GPER-dependent manner. Worthy, we demonstrated that the GPER-mediated increase of SERPINB2 is engaged in the anti-migratory and anti-invasive effects elicited by E4 in TNBC cells. In accordance with these findings, a correlation between SERPINB2 levels and a good clinical outcome was found in ER-negative breast cancer patients.
CONCLUSIONS: Overall, our results provide new insights into the mechanisms through which E4 can halt migratory and invasive features of TNBC cells.
A pharmaceutical compsn. for oral admin. comprises coagulation factor VIII and a protease inhibitor incorporated in liposomes. The compsn. is suitable for the treatment or prophylaxis of hemophilia. It is more easily handled than injection preparations and, when encapsulated, gives high absorption of the factor from the intestinal tract without being decomposed in the gastrointestinal tract. Pref. the compsn. is lyophilised to increase storage stability. Each component may be separately lyophilized before mixing and encapsulation. There may also be present stabilisers such as mannitol, albumin or dextran and additives to improve fluidity such as glucose and lactose. The coagulation factor may originate from humans or other mammals such as pigs and bovines. Protease inhibitors include aprotinin and dimethylcarbamoylmethyl p-(p-guanidino benzoyloxy) phenylacetate.
The subject invention provides materials and methods for providing immediate and long-term protection against pathogenic microorganisms. One aspect of the subject invention provides a vector, such as a lentiviral vector carrying a nucleic acid sequence encoding an antimicrobial peptide, such as dermcidin (DCD), as an efficient means of delivery of the peptide. Preferably, the vector has a tetracycline-dependent transcriptional regulatory system such that expression of the nucleic acid sequence encoding the antimicrobial peptide is effectively turned 'off' in the absence of tetracycline or its derivatives. Another aspect of the invention provides host cells that have been genetically modified with a vector of the invention to produce an antimicrobial peptide. Another aspect of the invention provides compositions comprising the vectors or host cells of the invention and a pharmaceutically acceptable carrier. Another aspect of the subject invention provides a method for treating or inhibiting the growth of a pathogenic microorganism by administering a vector or host cell of the invention to a subject suffering from, or susceptible to, infection by the pathogenic microorganism. Another aspect of the subject invention provides a method for detecting the presence of an antimicrobial peptide, such as DCD, within a male or female subject's urogenital tract.