anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Genomic instability is not only a hallmark of senescent cells but also a key factor driving cellular senescence, and replication stress is the main source of genomic instability. Defective prelamin A processing caused by lamin A/C (LMNA) or zinc metallopeptidase STE24 (ZMPSTE24) gene mutations results in premature aging. Although previous studies have shown that dysregulated lamin A interferes with DNA replication and causes replication stress, the relationship between lamin A dysfunction and replication stress remains largely unknown. Here, an increase in baseline replication stress and genomic instability is found in prelamin A-expressing cells. Moreover, prelamin A confers hypersensitivity of cells to exogenous replication stress, resulting in decreased cell survival and exacerbated genomic instability. These effects occur because prelamin A promotes MRE11-mediated resection of stalled replication forks. Fanconi anemia (FA) proteins, which play important roles in replication fork maintenance, are downregulated by prelamin A in a retinoblastoma (RB)/E2F-dependent manner. Additionally, prelamin A inhibits the activation of the FA pathway upon replication stress. More importantly, FA pathway downregulation is an upstream event of p53-p21 axis activation during the induction of prelamin A expression. Overall, these findings highlight the critical role of FA pathway dysfunction in driving replication stress-induced genomic instability and cellular senescence in prelamin A-expressing cells.
When probenecid is used to elevate plasma concentrations of penicillin or other beta-lactams, or when such drugs are given to patients taking probenecid therapeutically, high plasma concentrations of the other drug may increase the incidence of adverse reactions associated with that drug. In the case of penicillin or other beta-lactams, psychic disturbances have been reported.

The use of salicylates antagonizes the uricosuric action of probenecid (see WARNINGS). The uricosuric action of probenecid is also antagonized by pyrazinamide.

Probenecid produces an insignificant increase in free sulfonamide plasma concentrations, but a significant increase in total sulfonamide plasma levels. Since probenecid decreases the renal excretion of conjugated sulfonamides, plasma concentrations of the latter should be determined from time to time when a sulfonamide and probenecid are coadministered for prolonged periods. Probenecid may prolong or enhance the action of oral sulfonylureas and thereby increase the risk of hypoglycemia.

It has been reported that patients receiving probenecid require significantly less thiopental for induction of anesthesia. In addition, ketamine and thiopental anesthesia were significantly prolonged in rats receiving probenecid.

The concomitant administration of probenecid increases the mean plasma elimination half-life of a number of drugs which can lead to increased plasma concentrations. These include agents such as indomethacin, acetaminophen, naproxen, ketoprofen, meclofenamate, lorazepam, and rifampin. Although the clinical significance of this observation has not been established, a lower dosage of the drug may be required to produce a therapeutic effect, and increases in dosage of the drug in question should be made cautiously and in small increments when probenecid is being coadministered. Although specific instances of toxicity due to this potential interaction have not been observed to date, physicians should be alert to this possibility.

Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric action of probenecid, which probably is not significant under most circumstances.

In animals and in humans, probenecid has been reported to increase plasma concentrations of methotrexate (see WARNINGS).

Falsely high readings for theophylline have been reported in an in vitro study, using the Schack and Waxler technique, when therapeutic concentrations of theophylline and probenecid were added to human plasma.
BACKGROUND: When individuals follow a diet or limit their food intake, they activate cognitive restraint, which is defined as a mental effort to restrict dietary behavior with the goal of losing weight. As an example, fasting has also been associated with the recruitment of cognitive restraint, but further research is needed to fully understand its underlying mechanisms.
AIMS: The aim of this study was to examine the relationship between the duration of fasting and disordered eating, such as food cravings, binge eating, and potential changes in eating habits.
METHODS: An online survey was conducted among 853 first-semester university students to investigate their fasting practices and frequency over a three-month period prior to data collection. Participants who were on diets were excluded (n=214). After controlling the sample for biases, a comparison was made between 89 fasters and 369 non-fasters. The study compared levels of cognitive restraint, binge eating, food cravings, and consumption of 'forbidden' foods. A Poisson model was used to examine the association between hours of fasting and disordered eating traits. In the context of this study, the rate ratio was used to examine the relationship between fasting hours and disordered eating characteristics, such as binge eating and food cravings.
RESULTS: The study found that fasters experienced an increase in food cravings and binge eating. However, fasters consumed fewer bread slices than non-fasters. The rate ratio of fasting hours practiced is 115% higher among binge eaters (RR 2.15; CI95% 1.70-2.73) compared to those who did not binge. The rate ratio of fasting hours is 29% higher in participants with moderate binge eating (RR 1.29; CI95% 1.05-1.59), increasing to 140% (RR 2.40; CI95% 1.86-3.11) in people with severe binge eating. As for food cravings (state), the rate ratio was 2% higher (RR 1.02; CI 95% 1.01-1.03) for each increase in the unit of the scale.
CONCLUSIONS: Our study has indicated that fasting is positively associated with increased levels of binge eating and food cravings.
Participants will complete 6 sessions of the FLS peg transfer task over a 7-day time span. Participants randomized to this cohort had tdcs applied over the bilateral M1 areas of the brain by measurement of 20% length of periauricular distance left and right of the vertex. The anode was placed on the left side and the cathode was placed on the right side.
FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to coloproctology, and can be used for surgical management of chronic inflammation of epithelial coccygeal passage. After excising the epithelial coccygeal opening, the outer fistulous orifices are excised by enclosing incisions at the skin depth. In the upper and lower angles of the wound, perpendicular to it, additional incisions are made on both gluteal regions with their length equal to 1/3 of the buttock height plus a wound width from the middle line to its edge. Skin with subcutaneous fat is mobilized for this length to pre-excised external fistulous holes. Mobilized flap with subcutaneous fat is turned, pathologically changed tissues are removed with previously isolated external fistulous holes, wound in a wall administered platelet-rich plasma with platelet 106/mcl, using a syringe with injection needle 1.0 BogMark 0.5 × 16. Wound is closed from the bottom up by suturing with a double synthetic suture; the sacrococcyceal ligaments are grasped with a stitch length of 1.0–1.5 cm. Ends of the first suture at 2/3 of the wound depth are used to suture the subcutaneous tissue of one of the wound walls in the form of P-shaped seam. Second suture is similar to the other wound wall. Nasal sutures are fastened. Then by ends of the first suture at both sides, wound edges are intracutaneously grasped, which are brought down and fixed to bottom of sutured to 2/3 of wound depth by binding ends of this thread, similarly performed with the ends of the second suture, obtaining two nodal intracutaneous sutures at distance of 1.0 to 1.5 cm from each other with subsequent repetition with the filaments of all superimposed required for suturing, with the possibility of forming an intergluteal fold and a path in the form of a narrow strip with a width of up to 0.5 cm with the possibility of an outflow of a wound discharge, and additional incisions on the buttocks are closed with an intracutaneous suture.EFFECT: method enables simplifying surgical intervention, reducing the length of operation and the length of postoperative recovery ensured by simultaneous complete removal of fistulous holes.1 cl, 6 dwg, 4 ex
BACKGROUND: Nutrition and exercise are important interventions for sarcopenia. There were few studies on oral oligopeptide nutrition preparations combined with exercise to intervene in the older people with sarcopenia. The aim of this study was to verify the effectiveness of oligopeptide nutrition preparation combined with exercise intervention on the older people with sarcopenia in community.
METHODS: A total of 219 subjects aged 65 years or older with sarcopenia were randomly divided into 4 groups. The nutrition group (n = 58) was given individualized nutrition education and oral oligopeptide nutrition preparation. The exercise group (n = 50) received exercise intervention. The combined group (n = 52) received both oral nutrition preparation and exercise interventions. The control group (n = 59) only received individualized nutrition education. The nutrition preparation can provide energy 185kcal and protein 24.2g per day. The exercise intervention including warm-up exercise, resistance exercise and aerobic exercise, the training time was 60min for 5 times every week. The intervention lasted for 16 weeks. Hand grip strength, gait speed, body composition and hematology parameters were measured before and after intervention.
RESULTS: A total of 159 subjects completed the study. Compared with baseline, the left grip strength and 6-m walking speed of the subjects in nutrition group increased significantly after the intervention, and the grip strength of both hands in exercise group and combined group increased significantly. The body weight of the subjects in nutrition group, exercise group and combined group increased significantly after intervention, but no increase in soft lean mass (SLM) and skeletal muscle mass (SMM) was observed in any of the four groups. The fat-free mass (FFM) of the legs of the control group, exercise group and nutrition group decreased after intervention, and only the FFM of the legs of the combined group maintained the level before the intervention.
CONCLUSION: Both oral peptide nutrition and exercise interventions can improve the muscle strength or function of the older people with sarcopenia. However, there were no increases in muscle mass observed.
TRIAL REGISTRATION: ChiCTR, ChiCTR2100052135. Registered 20 October 2021, https://www.chictr.org.cn/showproj.html?proj=135743.
The invention provides a nano-preparation of electronegative antibiotic. The nano-preparation mainly comprises chitosan and the electronegative antibiotic. The electronegative antibiotic is prepared into chitosan-electronegative antibiotic nanoparticles through an ion crosslinking method. The method is simple in preparation process and operation; no organic solvent is used; nanoparticles with uniform diameters are obtained; and the method has good reproducibility. The pharmacological activity of the antibiotic nanoparticles is as good as raw materials. The antibiotic nanoparticles have advantages such as a broad antimicrobial spectrum and a low toxic and side effect. By preparing the nanoparticle preparation, the purpose of safe, effective, reliable treatment can be achieved.
Malignant pleural effusion is a common complication of malignant tumor, which usually indicates that the patient has reached the advanced stage, and about 30-40% of the patients are stubborn and refractory cases. The lack of standard therapeutic drugs and protocols in clinical practice seriously affects the anti-tumor treatment effect, quality of life and survival time of patients, and the prognosis is poor. IFN-γ can significantly induce the high expression of the costimulatory molecule ICAM-1 on tumor cells, thereby enhancing the killing of TUMOR cells by T cells. Moreover, IFN-γ can enhance the activity of CAR T cells in the presence of PD-L1-PD-1 pathway, and significantly improve the therapeutic effect of T cells on solid tumors. IFN-γ is an approved clinical treatment with known side effects and well-established symptomatic treatment. Although CIK is not a clinically approved drug, it has been used on a large scale in China with good safety and has entered the medical insurance of some provinces and cities. Tcm is an improved CIK cell and has good safety. Many clinical studies have been carried out, and no serious toxic and side effects have been observed.
Acute cholangitis is an acute inflammation caused by obstruction of the bile duct, of which choledocholithiasis is the most common cause. Without timely removal of the obstruction or control of the infection, cholangitis can get worse and even become life-threatening. Therefore, timely and effective treatment is essential for patients with acute cholangitis combined with choledocholithiasis. Endoscopic retrograde cholangiography (ERCP) is used as the first-line treatment for choledocholithiasis-associated acute cholangitis. Previous guidelines recommended two-session endoscopic therapy. Endoscopic biliary drainage as the initial treatment, followed by endoscopic stone extraction after cholangitis improved. In recent years, studies have found that single-session endoscopic stone extraction is safe and effective for patients without serious organ function impairment. Meanwhile, single-session endoscopic lithotomy can avoid the second ERCP intervention, which can relieve the pain of patients, reduce medical costs and shorten the length of hospital stay. However, there is still insufficient evidence on the effectiveness and safety of early single-session ERCP lithotomy. The aim of this study is to evaluate the efficacy and safety of single-session endoscopic stone extraction for acute cholangitis associated with choledocholithiasis, so as to provide reference of clinical treatment.

In a retrospective analysis, approximately 600 patients with acute cholangitis accompanied with choledocholithiasis, who treated with single-session or two-session endoscopic stone extraction at Beijing friendship hospital were studied. The investigators assessed the outcomes of single-stage and two-stage endoscopic stone extraction.
Gel including a phase-change material and a gelling agent. In one embodiment, the phase-change material may be n-tetradecane and/or n-hexadecane. The gelling agent, which may constitute up to about 10%, by weight, of the gel, may be a high molecular weight styrene-ethylene-butylene-styrene (SEBS) triblock copolymer with a styrene:rubber ratio of about 30:70 to 33 :67 % by weight. To form the gel, the phase-change material and the gelling agent may be mixed at a temperature at which the phase-change material is in a liquid state and which is below the flash point of the phase-change material and at which the mixture is not a viscoelastic liquid, whereby a non-homogeneous mixture is produced. The non- homogeneous mixture may then be heated to a temperature that is below the flash point of the phase-change material and at which a viscoelastic liquid is formed. The viscoelastic liquid may then be cooled to room temperature.
Participants will receive macular laser treatment at Baseline and then according to laser re-treatment criteria up to week 24. Participants will receive treatment with Intravitreal Aflibercept Injection (IAI) starting at week 24 if they met rescue criteria. Treatment with IAI once initiated was 3 initial monthly doses followed by Q8 week dosing.
Multiple Myeloma (MM) is a plasma cell malignancy that makes up 1% of all cancers and 10% of hematologic neoplasma, and is the second most commonly diagnosed hematologic malignancy. There are an estimated 20,520 new cases of MM and 10,610 deaths due to MM in the United States. Historically, standard first-line therapy for MM consisted of combination therapy with an alkylating agent, such as melphalan and prednisone. Response rates with such combination therapy are approximately 50%, but five-year survival rates remain low at 33%. For younger patients, debulking chemotherapy followed by autologous stem cell transplant (ASCT) with melphalan is the treatment of choice to increase the potential for a sustained durable remission. However, a large percentage of patients diagnosed with MM are not suitable candidates for ASCT because of age or comorbidities. The approach to MM treatment has undergone a radical transformation over the past decade with the introduction of the proteasome inhibitor, bortezomib, and immunomodulatory drugs (ImiDs), thalidomide or lenalidomide. Despite some advances in the treatment of MM, the disease remains incurable due to the persistence of minimal residual disease. Thus, novel modalities complementing or improving current treatment options are needed.

There is ample evidence that immunomodulatory drugs are effective against myeloma. Lenalidomide and thalidomide have been shown to stimulate T cells in the presence of antigen presenting cells via costimulatory pathway. Also, modulation of NK cell function has been associated with anti-tumor activity observed in MM patients treated with lenalidomide. It has been demonstrated that NK cells exhibit potent anti-MM activity following IL-2 administration, and ex vivo IL-2-activated and intravenously administered NK cells prolong survival in MM-bearing mice. Thus further demonstrating the role and importance of NK cells in the treatment of MM. Taken together, these data suggest that the use of a potent immunotherapeutic is an attractive approach to provide durable immune responses to or even potentially curing patients with MM.

Additionally, immunotherapy is a well-established approach for treating other cancer types. One strategy that has received attention is treatment with cytokines such as IL-2 to enhance anti-tumor immunity. Unfortunately, the considerable toxicity associated with this treatment makes it difficult to achieve an effective dose at the site of the tumor and limits the population that can be treated. Thus, there is a critical need for innovative strategies that enhance the effects of IL-2, reduce its toxicity without compromising clinical benefit, provide a more convenient dosing regimen, and treat other diagnoses including MM.

Altor Bioscience Corp. has developed a tumor-targeted IL-2 fusion protein, ALT-801, comprising human recombinant IL-2 genetically linked to a TCR domain capable of binding a tumor associated human p53 peptide presented in the context of HLA-A2.
Remodulin (1.0, 2.5, 5 and 10 mg/ml formulations as available) will be administered by continuous subcutaneous infusion via a subcutaneous cannula using a microbore infusion tubing set and a micro infusion pump. While hospitalized, initiation will begin at approximately 2.0 ng/kg/min with dose increments of 1-2 ng/kg/min approximately every 12 hours according to clinical response and tolerability. Following subject discharge, the dose rate should be increased by 1-2 ng/kg/min with dose increments separated by at least 24 hours. When a dose rate of 20 ng/kg/min has been achieved the dose increments can be increased up to 4 ng/kg/min with dose increments separated by at least 24 hours. The aim is to achieve a dose rate of at least 10, 20, 30 and 40 ng/kg/min by the end of Weeks 1, 4, 8 and 12, respectively.
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the necessity for multifaceted treatment strategies, including preoperative treatment (PT), which can enhance surgical outcomes and provide prognostic insights. This study aims to clarify the impact of PT-induced changes in mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) expression, potentially informing tailored treatment strategies and improving clinical outcomes for CRC patients.
METHODS: This retrospective study analyzed 120 paired samples from CRC patients who underwent preoperative treatment, comparing pre- and post-treatment specimens. A control group of 60 untreated surgical specimens was also included. Immunohistochemistry assessed MMR proteins (MSH6, MSH2, MLH1, PMS2) and HER2 expression. MSI status was determined in samples with low MMR expression.
RESULTS: Compared to pre-treatment samples, post-treatment samples exhibited lower levels of MSH6, MSH2, and total MMR expression, along with higher levels of HER2 expression. However, when compared to the untreated control group, there were no significant differences in the expression of MSH6, total MMR, and HER2. All samples that exhibited weak MMR expression and those that shifted to deficient mismatch repair (dMMR) status following treatment had stable microsatellite status. No clear clinicopathological characteristics or prognostic factors were found to be associated with changes in MMR and HER2 expression, except for the use of fluorouracil or capecitabine, which was related to changes in total MMR scores. ypTNM stage and TRG scores were identified as independent factors affecting disease progression in our study.
CONCLUSIONS: PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.
PURPOSE:The titled external preparation containing a compound such as cetraxate, etc. CONSTITUTION:An external preparation for skin diseases containing a compound shown by the formula (n is 0-6). The compound shown by the formula consists of cis and trans geometrical isomers. Especially a trans form (cetraxate) of the compound where n=2 is used as an improved remedy for gastritis and gastric ulcer by oral administration through pharmaceutical action such as improvement in very small blood circulation of gastric mucosa, suppression of pepsinogen in the mucosa, suppression of gastric juice secretion by antikallikrein action, etc. Zona, pemphigus vulgaris, pustular proriasis, cust, eczema nummulare, decubitus, burn, impetigo, skin moniliasis, athlete's foot, hydroa, atopic dermatitis, etc. may be cited as the skin diseases to which the external preparation is applied. An ointment, cream, lotion, etc. may be cited as the dosage form. Administration may be carried out by applying proper amounts two-three times a day.