Persius/hicric huggingface dataset:
RE1-silencing transcription factor
RE1-Silencing Transcription factor (REST), also known as Neuron-Restrictive Silencer Factor (NRSF), is a protein which in humans is encoded by the REST  gene, and acts as a transcriptional repressor. REST is expressly involved in the repression of neural genes in non-neuronal cells. Many genetic disorders have been tied to alterations in the REST expression pattern, including colon and small-cell lung carcinomas found with truncated versions of REST. In addition to these cancers, defects in REST have also been attributed a role in Huntington Disease, neuroblastomas, and the effects of epileptic seizures and ischemia.

# Function
This gene encodes a transcriptional repressor which represses neuronal genes in non-neuronal tissues. It is a member of the Kruppel-type zinc finger transcription factor family. It represses transcription by binding a DNA sequence element called the neuron-restrictive silencer element (NRSE, also known as RE1). The protein is also found in undifferentiated neuronal progenitor cells, and it is thought that this repressor may act as a master negative regulator of neurogenesis. Alternatively spliced transcript variants have been described; however, their full length nature has not been determined. REST is found to be down-regulated in elderly people with Alzheimer's disease.
REST contains 8 Cys2His2 zinc fingers and mediates gene repression by recruiting several chromatin-modifying enzymes.
- NRSF bound to DNA and cofactors on each of its two cofactor binding domains.
NRSF bound to DNA and cofactors on each of its two cofactor binding domains.
- Chromatin remodeling occurs, causing the gene to be 'turned off'.
Chromatin remodeling occurs, causing the gene to be 'turned off'.
REST expression strongly correlates with increased longevity. REST levels are highest in the brains of people who lived up to be 90 - 100s and remained cognitively intact. Levels stayed high specifically in the brain regions vulnerable to Alzheimer's, suggesting that they might be protected from dementia. It is assumed that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid -protein toxicity. REST is also responsible for ischaemia induced neuronal cell death, in mouse models of  brain ischaemia. Ischaemia, which results from reduced blood profusion of tissues, decreasing nutrient and oxygen supply, induces REST transcription and nuclear accumulation, leading to the epigenetic repression of neuronal genes leading to cell death. The mechanism beyond REST induction in ischaemia, might be tightly linked to its oxygen-dependent nuclear translocation and repression of target genes in hypoxia (low oxygen) where REST fulfils the functions of a master regulator of gene repression in hypoxia.

# Interactions
RE1-silencing transcription factor has been shown to interact with RCOR1.
Recurrent corneal erosion overview

# Overview
Recurrent corneal erosion is a disorder of the eyes characterized by the failure of the cornea's outermost layer of epithelial cells to attach to the underlying basement membrane (Bowman's layer). The condition is frequently painful because the loss of these cells results in the exposure of sensitive corneal nerves.

# Causes
There is often a history of previous corneal injury (corneal abrasion or ulcer), but also may be due to corneal dystrophy or corneal disease.  In other words, one may suffer from corneal erosions as a result of another disorder, such as map dot fingerprint disease. 

# Diagnosis

## History and Symptoms
Symptoms include recurring attacks of acute ocular pain, foreign-body sensation, photophobia (i.e. sensitivity to bright lights), and tearing often at the time of awakening or during sleep when the eyelids are rubbed or opened.

## Physical Examination
Signs of the condition include corneal abrasion or localized roughening of the corneal epithelium, sometimes with map-like lines, epithelial dots or microcysts, or fingerprint patterns.

## Other Diagnostic Studies
The erosion may be seen by a doctor using the magnification of an ophthalmoscope, although usually fluorescein stain must be applied first and a blue-light used.  Opticians, optometrists and ophthalmologists have use of slit lamp microscopes that allow for more thorough evaluation under the higher magnification.  Mis-diagnosis of a scratched cornea is fairly common, especially in younger patients.

# Treatment

## Surgery
Where episodes frequently occur, or there is an underlying disorder, different types of curative procedures may be attempted:
use of therapeutic contact lens, controlled puncturing of the surface layer of the eye (anterior stromal puncture) and laser phototherapeutic keratectomy (PTK).
These all essentially try to allow the surface epithelium to reestablish with normal binding to the underlying basement membrane, the method chosen depends upon the location and size of the erosion.
Rifaximin warnings and precautions

# Warnings And Precautions

## Travelers Diarrhea Not Caused by Escherichia coli
XIFAXAN was not found to be effective in patients with diarrhea complicated by fever and/or blood in the stool or diarrhea due to pathogens other than Escherichia coli.
Discontinue XIFAXAN if diarrhea symptoms get worse or persist more than 24-48 hours and alternative antibiotic therapy should be considered.
XIFAXAN is not effective in cases of travelers diarrhea due to Campylobacter jejuni. The effectiveness of XIFAXAN in travelers diarrhea caused by Shigella spp. and Salmonella spp. has not been proven. XIFAXAN should not be used in patients where Campylobacter jejuni, Shigella spp., or Salmonella spp. may be suspected as causative pathogens.

## Clostridium difficile-Associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including XIFAXAN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon which may lead to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

## Development of Drug Resistant Bacteria
Prescribing XIFAXAN for travelers diarrhea in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

## Severe (Child-Pugh C) Hepatic Impairment
There is increased systemic exposure in patients with severe hepatic impairment. Animal toxicity studies did not achieve systemic exposures that were seen in patients with severe hepatic impairment. The clinical trials were limited to patients with MELD scores <25. Therefore, caution should be exercised when administering XIFAXAN to patients with severe hepatic impairment (Child-Pugh C)
Right bundle branch block overview

# Overview
Right bundle branch block (RBBB) results from a defect in the heart's electrical conduction system. There is a delay in failure of transmission of electrical impulses down the right bundle of the heart.  As a result, the right ventricle depolarizes by an alternate mechanism. This is by means of cell-to-cell conduction. These cell to cell conduction impulses spread more slowly than usual from the interventricular septum to the left ventricle and to the right ventricle. This delay in conduction results in the characteristic ECG pattern which is a wide and notched QRS. Although conduction down the right bundle is delayed, conduction down the left bundle  is normal. As a result, the interventricular septum and left ventricle depolarize in the normal fashion.

# Epidemiology and Demographics
Prevalence of RBBB increases with age.

# Diagnosis

## Physical Examination
Right bundle branch block is associated with a persistently split second heart sound with normal respiratory variation in the splitting interval.

## Laboratory Findings
If there is a history of blunt trauma or any symptoms to suggest polymyositis, then troponin, creatine kinase (CK) and an echocardiogram should be obtained.

## Electrocardiogram
Criteria for complete right bundle branch block include: a QRS duration of > .12 seconds, an rSR' pattern with a wide terminal R wave in V1 and a qRS complex with a wide S wave in V6.

# Treatment

## Medical Therapy
In general treatment for right bundle branch block is not necessary.  These patients need not limit their activity.  However, if the RBBB progresses to heart block, the patient may be at risk for adverse clinical outcomes. In these patients further electrophysiologic testing may be necessary. Those patients who develop right bundle branch block after surgery should undergo EKG testing each year to evaluate for interval changes.  In particular, care should be taken to observe for the development of sinus bradycardia supraventricular or ventricular ectopy.
Rizatriptan nonclinical toxicology

# Nonclinical Toxicology

### 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: Oral carcinogenicity studies were conducted in mice (100 weeks) and rats (106 weeks) at doses of up to 125 mg/kg/day. Plasma exposures (AUC) at the highest dose tested were approximately 150 (mice) and 240 times (rats) that in humans at the maximum recommended daily dose (MRDD) of 30 mg/day. There was no evidence of an increase in tumor incidence related to rizatriptan in either species.
Mutagenesis: Rizatriptan was neither mutagenic nor clastogenic in a battery of in vitro and in vivo genetic toxicity studies, including: the microbial mutagenesis (Ames) assay, in vitro mammalian cell mutagenesis and chromosomal aberration assays, and the in vivochromosomal aberration assay in mouse.
Impairment of Fertility: In a fertility study in rats, altered estrus cyclicity and delays in time to mating were observed in females treated orally with 100 mg/kg/day rizatriptan. The no-effect dose was 10 mg/kg/day (approximately 15 times the human exposure at the MRDD). There were no other fertility-related effects in the female rats. There was no impairment of fertility or reproductive performance in male rats treated with up to 250 mg/kg/day (approximately 550 times the human exposure at the MRDD).
Robust Sandwich Covariate Estimate

# Overview
The Robust Sandwich Covariate Estimate, also known as the Huber Sandwich Estimator and the Robust Sandwich Estimator, can be used to estimate the variance of an ordinary least squares (OLS) regression when the underlying model is incorrect, such as in the case of homoscedasticity.  The Sandwich Estimator is generally only used when the OLE model has serious error and may benefit the variance, but the parameters being estimated by the OLE become meaningless to interpret .

# When to use it?
When trying to estimate standard error from data where heteroscedasticity is present (referring to the circumference in which the variability of a variable is unequal across the range of values of a second variable that it predicts). When estimating from heteroscedastic data, the ordinal least squares estimator will be consistent, but the estimated standard errors will be biased due to inequality in the dependent variables value across the independent variable.

# How does it work?
For OLS, you can imagine that you're using the estimated variance of the residuals (under the assumption of independence and homoscedasticity) as an estimate for the conditional variance of the  dependent variable. In the sandwich based estimator, you're using the observed squared residuals as a plug-in estimate of the same variance which can vary between observations. By using the square of the residuals, we get consistent estimates for the variance of the independent variables (the coefficients used in the model). These observed squared residuals will clean up any unexplained error due to heteroscedasticity that would otherwise been unexpected under the assumption of the constant covariance.
Rosiglitazone detailed information

# Overview
Rosiglitazone is an anti-diabetic drug in the thiazolidinedione class of drugs. It is marketed by the pharmaceutical company GlaxoSmithKline as a stand-alone drug (Avandia)  and in combination with metformin (Avandamet) or with glimepiride (Avandaryl).
Like other thiazolidinediones, the mechanism of action of rosiglitazone is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPAR. Rosiglitazone is a selective ligand of PPAR, and has no PPAR-binding action.
Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFB) levels fall and inhibitor (IB) levels increase in patients on rosiglitazone.
Recent research has suggested that rosiglitazone may also be of benefit to a subset of patients with Alzheimer's disease not expressing the ApoE4 allele.  This is the subject of a clinical trial currently underway.

# Side-effects and contraindications
A press release by GlaxoSmithKline in February 2007 noted that there is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide. The information was based on data from the ADOPT trial.
An article by Dr. Steven Nissen and his colleague Kathy Wolski in the June 14, 2007 issue of The New England Journal of Medicine reported that the use of rosiglitazone was associated with a slightly increased risk of heart attack (odds ratio=1.43). The FDA issued an alert on May 21 2007.
The findings of the study by Stevens and Wolski were considered enough of a public health matter to have caused the New England Journal of Medicine to release the findings online several weeks before they were to appear in print.
On July 30, 2007 an Advisory Committee of the Food and Drug Administration concluded that the use of rosiglitazone for the treatment of type 2 diabetes was associated with a greater risk of "myocardial ischemic events" (including heart attacks) than a placebo, metformin, or sulfonylurea. The FDA Advisory Committee recommended that label warnings and educational efforts to this effect be instituted immediately. An article by the committee chairman, Dr. Clifford J. Rosen, called "The Rosiglitazone Story -- Lessons from an FDA Advisory Committee Meeting" appeared in the August 30, 2007 issue of The New England Journal of Medicine.
On September 11, 2007, a research found diabetes drug Actos (by Takeda Pharmaceutical Co.) cuts the risk of heart attack, stroke and death, but raises the risk of heart failure, while rival Avandia  (by GlaxoSmithKline) raises heart risks.
Sandbox:Hyperlipoproteinemia type5

# Overview

# Historical Perspective

# Classification

# Pathophysiology

# Causes

# Differentiating Any Disease from other Diseases

# Epidemiology and Demographics

# Risk Factors

# Screening

# Natural History, Complications and Prognosis
A reduced HDL-C level is associate with ASCVD

# Diagnosis
Diagnosis of HLP type 5 is usually by clinical presentation.
- History (including age of onset of symptomes in the patient and family members).
- Physical findings such as eruptive xanthomas and tendon xanthomas.
- Laboratory evaluation such as lipid levels and apolipoprotein assays.
History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies

# Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
The evaluation and treatment decisions of type 5 HLP should be based on patient-centered and individual circumstances. Lifestyle therapies, such as appropriate nutrition and physical activity, are important elements of ASCVD risk reduction, with or without lipid-altering drug therapy. For patients in whom lipid-altering drug therapy is indicated, statin treatment is the primary pharmacologic modality for reducing ASCVD risk.

### Clinical algorithm for screening and management of elevated TG

## Medical Therapy
When the triglyceride concentration is very high (500 mg/dL, and especially if 1000 mg/dL), the primary goal of therapy is to reduce the triglyceride level to <500 mg/dL for the intent of reducing the risk of pancreatitis.
When triglycerides are between 200 and 499mg/dL, the primary targets of lipid therapy are nonHDL-C and LDL-C for the purpose of reducing ASCVD risk.
NonHDL-C comprises the cholesterol carried by all atherogenic particles, including LDL, intermediatedensity lipoproteins, very low-density lipoproteins (VLDL) and VLDL remnants, chylomicron remnants, and lipoprotein.

## Secondary Prevention
- Lifestyle interventions are a key to efforts to reduce triglycerides that includes
weight loss if overweight or obese
physical activity ( 150 minutes per week of moderate or higher intensity activity)
- weight loss if overweight or obese
- physical activity ( 150 minutes per week of moderate or higher intensity activity)
- Restriction of alcohol
- Restriction of sugar/refined carbohydrate intakes
- For patients with very high TG level (500 mg/dL),chylomicronemia will generally be present. For such patients, a low-fat diet (,15% of energy) may be helpful to reduce entry of new chylomicron particles into the circulation.
- For patients with triglycerides <500 mg/dL, partial replacement of dietary carbohydrate (especially sugars and other refined carbohydrates) with a combination of unsaturated fats and proteins may help to reduce the triglyceride and non-HDL-C concentrations.

# Case Studies
Case #1
Serratus posterior superior muscle

# Overview
The Serratus posterior superior is a thin, quadrilateral muscle, situated at the upper and back part of the thorax.
It arises by a thin and broad aponeurosis from the lower part of the ligamentum nuchae, from the spinous processes of the seventh cervical and upper two or three thoracic vertebr and from the supraspinal ligament.
Inclining downward and lateralward it becomes muscular, and is inserted, by four fleshy digitations, into the upper borders of the second, third, fourth, and fifth ribs, a little beyond their angles.
Simplified Geneva Score calculator

# Simplified Geneva Score Calculator
A one-point simplified scoring system replaced the previously weighted scores for each parameter. This was done to reduce the likelihood of error when the score is used in clinical settings. The simplified Geneva score does not lead to a decrease in diagnostic utility when compared to the previous Geneva scores.

## Calculation of the Simplified Geneva Score for PE
This handy calculator computes the pre-test probability of pulmonary embolism using simplified Geneva criteria.
Check all boxes that apply to your patient:
function calcScore(){
var score = 0;
if(document.forms.checked == 1){score += 1;}
if(document.forms.checked == 1){score += 1;}
if(document.forms.checked == 1){score += 1;}
if(document.forms.checked == 1){score += 1;}
if(document.forms.checked == 1){score += 1;}
if(document.forms.checked == 1){score += 1;}
if(document.forms.checked == 1){score += 1;}
if(document.forms.checked == 1){score += 2;}
if(document.forms.checked == 1){score += 1;}
document.forms.value = score;
if(score <= 1){document.forms.value = "Low probability of PE (7.7%)";}
if(score >= 2 && score <= 4){document.forms.value = "Intermediate probability of PE (29.4%)";}
if(score >= 5){document.forms.value = "High probability of PE (64.3%)";}

## Interpretation of the Simplified Geneva Score for PE
Shown below is the interpretation of the simplified Geneva score:
- Score 0-1 points: Low probability of PE (7.7%)
- Score 2-4 points: Intermediate probability of PE (29.4%)
- Score 5 points: High probability of PE (64.3%)
- Score 0-2 points: PE is unlikely (11.5%)
- Score 3 points: PE is likely (41.6%)
Small nuclear ribonucleoprotein D2
Small nuclear ribonucleoprotein Sm D2 is a protein that in humans is encoded by the SNRPD2 gene.
The protein encoded by this gene belongs to the small nuclear ribonucleoprotein core protein family. It is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified.

# Interactions
Small nuclear ribonucleoprotein D2 has been shown to interact with DDX20, Small nuclear ribonucleoprotein D1, Small nuclear ribonucleoprotein polypeptide F, CDC5L and SMN1.
Solute carrier family 25 member 22
Solute carrier family 25 member 22 is a protein that in humans is encoded by the SLC25A22 gene. This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Expression of this gene is increased in colorectal tumor cells.

# Structure
The SLC25A22 gene is located on the p arm of chromosome 11 in position 15.5 and has 9 exons spanning 7,807 base pairs. The gene produces a 34.5 kDa protein composed of 323 amino acids. The encoded protein is a multi-pass transmembrane protein located in the mitochondrial inner membrane.

# Function
The protein encoded by SLC25A22 is involved in the transport of glutamate, cotransported with H+, across the inner mitochondrial membrane. Both SLC25A22 and SLC25A18 are mitochondrial glutamate/H+ symporters.

# Clinical significance

## Epileptic encephalopathy
Mutations in the SLC25A22 gene cause early infantile epileptic encephalopathy 3 (EIEE3), a severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Epileptic encephalopathy early infantile type 3 is characterized by a very early onset, erratic and fragmentary myoclonus, massive myoclonus, partial motor seizures and late tonic spasms. The prognosis is poor, with no effective treatment, and children with the condition either die within 1 to 2 years after birth or survive in a persistent vegetative state.
Migrating partial seizures in infancy, caused by a specific G110R mutation in the SLC25A22 gene, can be inherited.
Although expression of SLC25A22 is high in most tissues, expression is particularly strong in the developing brain, with regions of the brain involved in the genesis and control of myoclonic seizures specifically expressing SLC25A22 during human development.

## Colorectal cancer
SLC25A22 expression is increased in colorectal tumor tissues compared to matched nontumor colon tissues. Increased expression of the encoded protein was associated with decreased survival times in colorectal cancer patients. Knockdown of this gene in mutant colorectal cells decreased their migration, proliferation, and invasion.

# Interactions
The encoded protein interacts with SLC38A1, NDUFAF4, and 43 other proteins.