anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.
OBJECTIVE: To assess the agreement between cardiac output (CO) estimated via evaluation of the arterial pressure waveform by a novel monitoring system (Edwards Acumen IQ sensor and HemoSphere Advanced Monitor Platform [HS-IQ]; Edwards LifeSciences) and measured by thermodilution (TD) in anesthetized, normovolemic, and hypovolemic dogs. To assess the agreement between the HS-IQ CO measurements in the radial artery and dorsal metatarsal artery.
ANIMALS: 8 purpose-bred Beagles.
METHODS: Dogs were placed under general anesthesia. CO was measured via TD and via the HS-IQ at radial and dorsal metatarsal arterial catheters. CO measurements were obtained at 4 time points including normovolemic and multiple hypovolemic states. Paired measurements of CO were evaluated via the method of Bland and Altman with acceptable limits of agreement (LOA) defined as < 30%.
RESULTS: A total of 24 (dorsal metatarsal) and 21 (radial) paired measurements were collected in 8 dogs. The overall bias (CI) for comparison of TD to radial arterial HS-IQ CO measurements was -0.09 L/min. LOA and proportional LOA were -2.66 to 2.49 L/min and -140.72% to 104.94%. The overall bias (CI) for comparison of TD to dorsal metatarsal arterial HS-IQ CO measurements was -0.26 L/min. LOA and proportional LOA were -2.76 to 2.24 L/min and -135.96% to 93.25%. The overall proportional error for radial arterial was -17.9% and for dorsal metatarsal was -21.4%.
CLINICAL RELEVANCE: CO measurements with the HS-IQ were easy to obtain but did not produce results within a clinically acceptable range for either measurement site, with a very wide LOA. The CO estimations from the HS-IQ are not appropriate for clinical use at this time.
Phenotypic associations have been reported between heart failure (HF) and blood lipids (BLs), blood pressure (BP), and blood glucose (BG). However, the shared genetic etiology underlying these associations remains incompletely understood. Conducting a large-scale multi-trait association study for HF with these traits, we discovered 143 previously unreported genomic risk loci for HF. Results showed that 46, 35, and 14 colocalized loci were shared by HF with BLs, BP, and BG, respectively. Notably, the loci shared by HF with these traits rarely overlapped, indicating distinct mechanisms. The combination of gene-mapping, gene-based, and transcriptome-wide association analyses prioritized noteworthy candidate genes (such as lipoprotein lipase [LPL], G protein-coupled receptor kinase 5 [GRK5], and troponin C1, slow skeletal and cardiac type [TNNC1]) for HF. Enrichment analysis revealed that HF exhibited comparable characteristics to cardiovascular traits and metabolic traits correlated to BLs, BP, and BG. Finally, we reported drug repurposing candidates and plasma protein targets for HF. These results provide biological insights into the pathogenesis of these comorbidities of HF.
Many germline mutations have been implicated in breast cancer pathogenesis and despite several studies on occult atypical lesions in prophylactic mastectomy specimens from patients with BRCA1/2 mutations, there are very limited data on other genes associated with increased breast cancer risk and the distribution of lesions in patients with hereditary breast cancer. We identified 207 patients who underwent bilateral prophylactic mastectomy due to germline mutations in BRCA1/2, PALB2, CHEK2, ATM, CDH1, PTEN, BARD1, or strong family history between 2015 and 2023. Patients with biopsy-proven past or current invasive breast carcinoma or carcinoma in-situ preoperatively were excluded. In addition to multiple benign lesions, the following atypical lesions were identified: flat epithelial atypia (16.9%), atypical ductal hyperplasia (14.0%), lobular neoplasia (14.0%), ductal carcinoma in-situ (4.3%), invasive ductal carcinoma (0.4%). Both low-grade and high-grade pathway lesions were identified in this cohort, and in a subset of patients, they co-occurred. The frequency of atypical lesions identified in patients with strong family history were comparable to those with proven germline mutation. PTEN immunohistochemistry showed loss of expression in ductal carcinoma in-situ and tubular adenomas in PTEN-mutant patients. Overall, findings from this cohort support the benefit of prophylactic mastectomy in patients with germline mutations and/or strong family history. Additionally, this is the first demonstration that PTEN immunohistochemistry may be helpful in identifying germline mutations in patients with atypical or neoplastic proliferations.
Participants will receive \[177Lu\]Lu- NeoB in combination with ribociclib and fulvestrant, in the dose escalation and the backfill parts of the study. Goserelin administration is only applicable for pre/peri-menopausal participants.
Participants received 1 or 2 doses of alteplase, 2 mg/mL, directly into the catheter lumen. Participants received the first dose at min 0, and the second dose (if needed) at min 90.
On Day 1, participants were challenged with 10\^6 colony-forming units (CFU) of freshly-harvested wild-type V. cholerae. At the onset of diarrhea, or at 48 hours after challenge, whichever occurred first, participants received oral iOWH032 500 mg tablets every 8 hours for 3 days. Participants received a 3-day course of antibiotics starting 4 days post-challenge, or sooner if the participant met the criterion for severe cholera diarrhea.
BACKGROUND: In 2021, Uganda's neonatal mortality rate was approximately 19 deaths per 1000 live births, with an estimated stillbirth rate of 15.1 per 1000 total births. Data are critical for indicating areas where deaths occur and why, hence driving improvements. Many countries rely on surveys like Demographic and Health Surveys (DHS), which face challenges with respondents' misinterpretation of questions. However, little is documented about this in Uganda. Cognitive interviews aim to improve questionnaires and assess participants' comprehension of items. Through cognitive interviews we explored women's interpretations of questions on pregnancy and pregnancy outcomes.
METHODS: In November 2021, we conducted cognitive interviews with 20 women in Iganga Mayuge health and demographic surveillance system site in eastern Uganda. We adapted the reproductive section of the DHS VIII women's questionnaire, purposively selected questions and used concurrent verbal probing. Participants had secondary school education and were English speaking. Cognition was measured through comparing instructions in the DHS interviewers' manual to participants' responses and researcher's knowledge. A qualitative descriptive approach to analysis was undertaken.
RESULTS: We report findings under the cognitive aspect of comprehension. Some questions were correctly understood, especially those with less technical terms or without multiple sections. Most participants struggled with questions asking whether the woman has her living biological children residing with her or not. Indeed, some thought it referred to how many living children they had. There were comprehension difficulties with long questions like 210 that asks about miscarriages, newborn deaths, and stillbirths together. Participants had varying meanings for miscarriages, while many misinterpreted stillbirth, not linking it to gestational age. Furthermore, even amongst educated women some survey questions were misunderstood.
CONCLUSIONS: Population surveys may misclassify, over or under report events around pregnancy and pregnancy outcomes. Interviewers should begin with a standard definition of key terms and ensure respondents understand these. Questions can be simplified through breaking up long sentences, while interviewer training should be modified to ensure they thoroughly understand key terms. We recommend cognitive interviews while developing survey tools, beyond basic pre-testing. Improving respondents' comprehension and thus response accuracy will increase reporting and data quality.
The invention relates to a hollow mesoporous silicon dioxide sphere coated by a gold shell, a preparation method thereof and application thereof in tumor treatment. The invention takes hollow mesoporous silica spheres or hollow mesoporous silica spheres containing a core as the core, and the surface of the hollow mesoporous silica spheres is uniformly coated with a gold shell; the hollow mesoporous silica spheres are loaded with anti-tumor drugs, and the surface of the gold shell is further coupled with tumor specific targeting molecules. The size of the hollow mesoporous silica spheres and the thickness of the gold shell are controllable. According to the Mie scattering theory, the gold shell coated hollow mesoporous silica spheres can adjust the absorption of the hollow mesoporous silica spheres in the near infrared region, and can convert the light energy of near infrared laser into the surrounding heat energy for killing malignant tumor cells. The hollow mesoporous silica sphere can be used as a sustained and controlled release carrier of therapeutic drugs, and the tumor specific targeting molecule coupled to the surface of the gold shell enables the preparation to have a targeting function. The material is a multifunctional anti-tumor nano preparation integrating photothermal therapy, chemotherapy, high targeting and sustained and controlled release.
BACKGROUND: Complex regional pain syndrome type I is a pathological condition characterized by an exaggerated response of tissues to low or moderate pain stimuli. The exact pathogenesis and optimal medical treatment for complex regional pain syndrome type I are still not fully understood, although bisphosphonates have shown positive effects in reducing pain. Foot surgery can be complicated by the development of complex regional pain syndrome type I, leading to functional decline and difficulties in weight-bearing.
CASE PRESENTATION: The authors present a clinical case involving complex regional pain syndrome type I that developed after surgical foot arthrodesis. The patient, a 42-year-old Caucasian male, did not respond to clodronate treatment but experienced successful outcomes upon the addition of teriparatide, which effectively stimulated the healing of arthrodesis.
CONCLUSION: Teriparatide cannot be considered the primary treatment for complex regional pain syndrome due to insufficient solid clinical data. However, when complex regional pain syndrome is associated with or caused by delayed union, teriparatide can be used to address the underlying cause of complex regional pain syndrome.
Currently, finasteride (FIN) is approved to treat androgenetic alopecia only orally, and the application of FIN in transdermal drug delivery system (TDDS) has introduced a new approach for treating the disease. This study was aimed to develop a FIN transdermal patch for the treatment of androgenetic alopecia(AGA) by combing ion-pair and O-acylmenthols (AM) as chemical permeation enhancers (CPEs). The formulation of patch was optimized though single-factor investigation and Box-Behnken design. The pharmacokinetics and androgenetic alopecia pharmacodynamics of the patch were evaluated. Additionally, the permeability enhancement mechanisms of ion-pair and AMs were explored at both the patch and skin levels. The effects of ion-pair and AMs on the patch were characterized by rheology study, FTIR, and molecular docking, and the effects on the skin were assessed through ATR-FTIR, Raman study, DSC, CLSM and molecular dynamics. The finalized formulation of FIN patches was consisted of 5 % (w/w) synthetic FIN-CA (Citric Acid), 6 % MT-C6 as CPEs, 25-AAOH as a pressure-sensitive adhesive (PSA), with a patch thickness of 80 ± 5 μm. The final Q24 h is 78.22 ± 5.18 μg/cm2. Based on the high FIN permeability, the pharmacokinetic analysis revealed that the FIN patch group exhibited a slower absorption rate (tmax = 7.3 ± 2.7 h), lower peak plasma concentration and slower metabolic rate (t1/2 = 6.2 ± 0.8 h, MRT0-t = 26.0 ± 7.8 h) compared to the oral group. Moreover, the FIN patch also demonstrated the same effect as the oral group in promoting hair growth in AGA mice. The results indicated that both FIN-CA and AMs could enhance the fluidity of the PSA and weaken the interaction between FIN-CA and PSA, thereby promoting the release of the FIN from the patch. The interaction sites on the skin for ion-pair and the four AMs were found in the stratum corneum (SC) of the skin, disrupting the tight arrangement of stratum corneum lipids. This study serves as a reference for the multi-pathway administration of FIN and the combination of ion-pair with AMs to enhance drug permeation.
The participants will be instructed to restrict the total daily calorie intake to 800 kcal by receiving the very-low-calorie meal replacement formula for 2 consecutive days per week. They will be allowed to maintain their normal diet in the remaining 5 days, but need to restrict total intake to 2000 kcal per day.
Children diagnosed with either Crohn's disease (CD) or Ulcerative Colitis (UC) under follow-up at the Pediatric gastroenterology institute, Schneider Children's Hospital, will be enrolled. Patients can be enrolled at diagnosis or at any time point during follow-up. Patients' characteristics will be retrieved from their medical files including demographic details, disease phenotype, anthropometric measures, laboratory evaluation, complication and therapeutic regimens. At enrollment all patients will perform body composition assessment by air displacement plethysmography (ADP) and DEXA (no greater than 7 days between the 2 methods of measurement). At one and two years following initial assessment ADP measurement will be repeated, mid arm circumference and skin fold measurements will be taken and the patient will fill a physical activity questionnaire. Disease activity score (either Pediatric Crohn's Disease Activity Index for CD or Pediatric Ulcerative Colitis Activity Index for UC) will be calculated. Similar evaluation will be performed prior and immediately following exclusive enteral nutrition or corticosteroid courses and prior to any biologic therapy initiation.
Cantharidin is the toxic component of blister beetles of the genus Epicauta. Cantharidin is a potent vesicant which causes blisters, erosions, and ulcerations in the gastrointestinal and urinary tracts, and can cause myocardial necrosis. Blister beetles are found over most of North America and specifically contaminate alfalfa at harvest. History of alfalfa feeding, with colic, dysuria, hypocalcemia, and hypomagnesemia are suggestive of blister beetle toxicosis. Myocardial damage causes increased serum cardiac troponin 1. Tentative diagnosis can be made by finding the beetles in feed or ingesta. Definitive diagnosis requires detection of cantharidin in urine or gastric contents. Treatment involves ending exposure, decreasing absorption, controlling pain, using gastroprotectants, and fluids and electrolyte replacement. Prognosis is guarded to poor.
It is a current opinion that muscular stretching is able to reduce pain and to allow increase of the opening excursion at the joints. To investigate this possibility in the face, the investigators developed a method of stretching associated with large dynamic jaws during chewing using a special device (Spring Device ®) for ten minutes, allowing the muscles of the oral cavity to relax. The height of the bite was set as two-thirds of the maximum opening (max. 2 cm.) of the mouth at rest (without forcing) thus avoiding maintaining the head of the condyle at maximum aperture for a long time. The subjects were then analyzed by means of kinesiography to determine the changes in the vertical dimension. Increasing stretching produces neuromuscular relaxation and a reduction of pain. This study showed that this therapy induces oral and extraoral pain reduction and increases neck mobility and mouth opening. The stimulation of trigeminal receptors is an important drive for therapy in the trigeminocardiac reflex (TCR).
The patient receive 2 different drug combinations on this study. The first combination will consist of an intensive chemotherapy regimen (cyclophosphamide, mesna, methotrexate, doxorubicin liposomal or doxorubicin, vincristine, ARA-C (cytarabine) and dexamethasone). The second combination will consist of another intensive chemotherapy regimen (methotrexate and Ara-C \[cytarabine\]).
FIELD: medicine, neurology. SUBSTANCE: one should preliminarily open a hematoencephalic barrier or make the possibility for medicinal preparation to come through this barrier. Cyclosporin A is used as a neuroprotector preparation or another preparation of cyclosporins' family. Ischemic insult is a lesion of central nervous system as a result of cerebrovascular diseases or hypoxia or brain trauma or neurodegenerative processes caused by Alzheimer's, Huntington's, Parkinson's diseases. EFFECT: higher efficiency of therapy. 5 cl, 1 dwg
Intervention consists of six 45-minute one-on-one sessions between a patient and a trainer, who teaches the Bright IDEAS stepwise approach to problem-solving and guides the participant through solving their own problems using the Bright IDEAS approach and worksheets. In addition, participants in this arm will receive a standardized list of resources from the National Comprehensive Cancer Network (NCCN) adolescent and young adult patient guidelines.
BACKGROUND: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery.
MATERIALS AND METHODS: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 months). Publication bias was assessed using Begg's test and Egger's test.
RESULTS: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery [total thyroidectomy (TT) vs. lobectomy], surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT, while preoperative PTH was a protective factor. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT.
CONCLUSION: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.
Dental compositions comprising a polymerizable compound, filler system of nanometer-sized silica particles, and polymerization system capable of bein g activated by light are provided. The compositions further contain a solven t such as a mixture of 1-butanol and acetone and may contain water. The nano meter-sized silica particles, having an average particle size of about 1 nm to about 100 nm, are uniformly dispersed within the resin. The compositions can be applied as a polish, sealant, bleach guard, or other coating material to the surfaces of dental restorations and teeth. Self-etching and non-self -etching compositions are provided. The cured coating forms a protective, du rable film that enhances the shine and luster of the restorations and teeth.
Erector spinae plane (ESP) block is a recently described technique which may be an alternative to Paravertebral block (PVB) for providing thoracic analgesia. It involves injection of local anesthetic into the fascial plane deep to erector spinae muscle. ESP is a more superficial block with a better defined end-point injection between the bony transverse process and erector spinae muscle. A more superficial ultrasound-guided block will be faster to perform and less painful for the patient. ESP does not have the same risk of pneumothorax as PVB.

Epidural analgesia has become the standard of care. Although thoracic epidurals provide excellent analgesia for the management of rib fractures, they are limited to a certain population due to patient factors and side-effects. Many trauma patients have other injuries which contraindicate the use of epidurals, or which prevent positioning for insertion. There are disadvantages to thoracic epidural analgesia. They are technically challenging to insert, with a risk of dural puncture or spinal cord injury. Adverse effects include hypotension, and if opioids used, urinary retention and pruritus. Patients can develop a motor block and are unable to mobilize with an epidural in situ.
We describe a 44-year-old man with a complaint of atonic seizures of the left upper limb, followed by generalized seizures. Brain MRI showed isolated juxtacortical white matter T2 hyperintensity with gadolinium (Gd) enhancement of the adjacent cortical gray matter and subcortical white matter in the right frontal convexity. Treatment with levetiracetam was effective for seizure suppression, and he had no other neurological abnormalities. Human leukocyte antigen typing revealed B54 and Cw1, which indicated the possibility of neuro-Sweet disease. However, a general examination, which included vital signs and eye and skin findings, was normal. A cerebrospinal fluid test showed a mild elevation in protein levels without pleocytosis and a normal range of interleukin-6. Electroencephalography showed intermittent slow waves without epileptic discharge in the bilateral temporal lobes. We detected subtle flow voids in the pia mater of the left frontal lobe, which suggested cerebrovascular disease, and specifically, the possibility of dural arteriovenous fistulas. Computed tomography angiography showed abnormally dilated perimedullary veins in the left frontal lobe. Cerebral angiography confirmed the existence of four dural arteriovenous fistulas, which included two retrograde leptomeningeal venous drainages in the right frontal cortical veins supplied by the anterior branch of the right middle meningeal artery. The other dural arteriovenous fistulas were retrograde leptomeningeal venous drainages in the left frontal cortical veins supplied by the anterior and posterior convexity branches of the left middle meningeal artery. The patient underwent successful endovascular embolization of all dural arteriovenous fistulas with Onyx injection. A follow-up MRI showed gradual improvement of the T2 hyperintensity and Gd enhancement. He remained seizure-free for 2 years following endovascular embolization.