Persius/hicric huggingface dataset:
Organ-limited amyloidosis
Organ-limited amyloidosis is a category of amyloidosis where the distribution can be associated primarily with a single organ. It is contrasted to systemic amyloidosis, and it can be caused by several different types of amyloid.
In almost all of the organ-specific pathologies, there is significant debate as to whether the amyloid plaques are the causal agent of the disease or instead a downstream consequence of a common idiopathic agent.  The associated proteins are indicated in parentheses.

# Neurological amyloid
- Alzheimer's disease (A 39-43)
- Parkinson's disease (alpha-synuclein)
- Huntington's disease (huntingtin protein)
- Transmissible spongiform encephalopathies caused by prion protein (PrP) were sometimes classed as amyloidoses, as one of the four pathological features in diseased tissue is the presence of amyloid plaques. These diseases include;
Creutzfeldt-Jakob disease (PrP in cerebrum)
Kuru (diffuse PrP deposits in brain)
Fatal Familial Insomnia (PrP in thalamus)
Bovine spongiform encephalopathy (PrP in cerebrum of cows)
- Creutzfeldt-Jakob disease (PrP in cerebrum)
- Kuru (diffuse PrP deposits in brain)
- Fatal Familial Insomnia (PrP in thalamus)
- Bovine spongiform encephalopathy (PrP in cerebrum of cows)

# Cardiovascular amyloid
- Cardiac amyloidosis
Senile cardiac amyloidosis-may cause heart failure
- Senile cardiac amyloidosis-may cause heart failure
- Congophilic angiopathy

# Other
- Amylin deposition can occur in the pancreas in some cases of type 2 diabetes mellitus
Prolactin-induced protein
Prolactin-inducible protein also known as gross cystic disease fluid protein 15 (GCDFP-15), extra-parotid glycoprotein (EP-GP), gp17 seminal actin-binding protein (SABP)  or BRST2 is a protein that in humans is encoded by the PIP gene. It is upregulated by prolactin and androgens and downregulated by estrogen.

# Function
The protein has a physiological function in regulation of water transport mainly in apocrine glands in the axilla, vulva, eyelid and ear canal, serous cells of the submandibular salivary gland, serous cells of the submucosal glands of the bronchi, and accessory lacrimal glands  as well as cutaneous eccrine glands. It is also found in amniotic fluid and seminal fluid.
PIP has the ability to bind  immunoglobulin G (IgG), IgG-Fc, CD4-T cell receptor suggesting a wide range of immunological functions. PIP also binds to AZGP1. PIP exerts aspartyl proteinase activity able to cleave fibronectin.
PIP can bind different species of bacteria showing highest affinity to sterptococci thus playing a role in non-immune defense of the body against pathogenic bacterial strains.
Mitogenic effect of PIP was observed on both normal and malignant breast epithelial cells.

# Use as marker and significance in disease
Prolactin induced protein (called GCDFP-15 in this context) in breast cyst fluid or breast tissue serves as marker of both benign and malignant apocrine metaplasia as the protein is not normally expressed in breast tissue. It is characteristic of low grade apocrine carcinoma of the breast, high grade apocrine carcinoma frequently loose expression of this marker.
PIP gene expression in breast cancer lines was associated with decreased cell proliferation and invasivenes and an increase of the apoptotic pathway. Many of the genes affected by PIP appear to be regulated by STAT5.
A mitogenic effect of this protein on experimental breast cells lines MCF10A, MCF7, BT474, MDA-MB231 and T47D  was detected. Prolactin-induced protein has also been used for identification and detection of disseminated breast cancer cells.
The PIP gene is amplified in some breast cancer lines accounting for some of its overexpression, however additional mechanisms are needed to completely explain its overexpression.
In T47D breast cancer cells, androgen receptor and RUNX2 interact to synergistically enhance PIP expression.
In molecular apocrine breast cancer (ER-/AR+) there is a positive feedback loop between androgen receptor and extracellular signal-regulated kinase (ERK) via CREB1 which can be inhibited by anti-androgens. PIP expression is necessary for viability and invasiveness of this subtype of breast cancer.
In ER+ breast cancer, particularly those with very high level of ER expression, PIP appears to play an important role in proliferation and invasion as well as acquired resistance to tamoxifen.
Positive predictive value
Assistant Editor(s)-In-Chief: Kristin Feeney, B.S.

# Overview
The positive predictive value (PPV) , or precision rate, is the proportion of individuals with a positive test result who actually have preclinical disease.  It is considered the physician's gold standard, as it reflects the probability that a positive test reflects the underlying condition of interest.

# Worked example

# Definition
The Positive Predictive Value can be defined as
 PPV = \frac{\rm number\ of\ True\ Positives}{{\rm number\ of\ True\ Positives}+{\rm number\ of\ False\ Positives}}
-r, alternatively,
 PPV = \frac{({\rm sensitivity}) ({\rm prevalence})}{({\rm sensitivity}) ({\rm prevalence}) + (1 - {\rm specificity}) (1-{\rm prevalence})} 

# Problems with Positive Predictive Value
- Predictive values are often used in medical research to evaluate the usefulness of a diagnostic test. Hence the PPV is used to indicate the probability that in case of a positive test, that the patient really has the specified disease. However there may be more than one cause for a disease and any single potential cause may not always result in the overt disease seen in a patient.
- An example is the microbiological throat swab used in patients with a sore throat. Usually publications stating PPV of a throat swab are reporting on the probability that this bacteria is present in the throat, rather than that the patient is ill from the bacteria found. If presence of this bacteria always resulted in a sore throat, then the PPV would be very useful. However the bacteria may colonise individuals in a harmless way and never result in infection or disease. Sore throats occurring in these individuals is caused by other agents such as a virus. In this situation the gold standard used in the evaluation study represents only the presence of a bacteria (that might be harmless) but not a causal bacterial sore throat illness. It can be proven that this problem will affect positive predictive value far more than negative predictive value. To evaluate diagnostic tests where the gold standard looks only at potential causes of disease, one may use an extension of the  predictive value termed the Etiologic Predictive Value.
- PPV is a function of the population sampled whereby a higher yield occurs in a higher risk group.
- PPV is influenced by sensitivity, specificity, prevalence, and diagnostic pre-clinical phase of disease.

# Related Chapters
- Negative predictive value
- Relevance (information retrieval)
- Receiver-operator characteristic
Paradoxical septal motion
Synonyms and keywords: PSM

# Overview
Paradoxical septal motion is defined as movement of the interventricular septum away from the left ventricular free wall during systole which is the opposite of its normal movement which is inward toward the left ventricle / or the left ventricular free wall during systole.

# Causes
- Arrhythmogenic RV dysplasia
- Atrial septal defect
- Constrictive pericarditis
- Following heart surgery. There may be altered LV function and lack of restraint on the pericardium if it is opened.
- Hibernation of the septal myocardium
- Myocardial infarction of the septal myocardium
- Ischemic heart disease involving the septal myocardium
- Left bundle branch block in 14/17 cases , particularly if the QRS is > 150 ms or if there is septal fibrosis
- Mitral stenosis
- Pericardial effusion (large)
- Following a pericardial incision
- Pulmonary embolism
- Pulmonary hypertension
- Repaired Tetralogy of Fallot
- Right ventricular hypertrophy
- Right ventricular pacing, particularly from the right ventricular outflow tract due to contraction of the RV before the LV
- Right ventricular tumor
- Right ventricular volume overload
- Stunning of the septal myocardium
- Wolff-Parkinson-White type B syndrome

# Risk Factors
Certain surgical procedures are independently associated with a higher risk of PSM:

## Risk Factors Associated with an Increased Risk of PSM
- Aortic valve surgery (p=0.02)
- Mitral valve surgery (p<0.001)
- Longer cardiopulmonary bypass time (p < 0.001)

## Risk Factors Associated with an Decreased Risk of PSM
- Coronary artery bypass grafting (CABG) than non-CABG surgery (p = 0.003)
- Off-pump coronary artery bypass (OPCAB)

# Diagnosis

## Echocardiography
Prostaglandin D2 receptor
Prostaglandin D2 receptor (DP), also known as PTGDR, is a receptor for prostaglandin D2, but also denotes the human gene encoding it.

# Mechanism
It is a G-protein-coupled receptor. The activity of it is mainly mediated by G-S proteins that stimulate adenylate cyclase resulting in an elevation of intracellular cAMP and Ca2+.

# Function
Knockout studies in mice suggest that the ligand of this receptor,  prostaglandin D2 (PGD2), functions as a mast cell-derived mediator to trigger asthmatic responses.  It also causes vasodilation
Pancreas divisum overview

# Overview
Pancreatic divisum is a congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts.  

# Diagnosis

## History and Symptoms
A majority of individuals born with pancreas divisum will never have symptoms for their entire life. In most cases, pancreas divisum is only detected during an autopsy of a person that is deceased. However, approximately 1% of those with pancreas divisum will develop symptoms during their lifetime. Symptoms commonly include abdominal pain, nausea and/or vomiting, and pancreatitis. A small number of individuals may develop chronic pancreatitis.

## Other Imaging Findings
The most common and accurate way of diagnosing an individual with this anomaly is by an ERCP. This test can demonstrate the presence of two separately draining ducts within the pancreas.

# Treatment

## Surgery
Pancreas divisum in individuals with no symptoms do not need treatment. Treatment of those with symptoms varies and has not been very well established. A surgeon may attempt a sphincterotomy by cutting the minor papilla to enlarge the opening and allow pancreas enzymes to flow normally. During surgery, a stent may be inserted into the duct to ensure that the duct will not close causing a blockage. As with any surgery, this operation is not risk-free. This surgery can cause pancreatitis in patients, or in rare cases, kidney failure and death.
Peritoneal inclusion cyst

# Overview
Peritoneal inclusion cysts represent a nonneoplastic reactive mesothelial proliferation. Peritoneal inclusion cysts occur almost exclusively in premenopausal women with a history of previous abdominal or pelvic surgery, trauma, pelvic inflammatory disease, or endometriosis. Peritoneal inclusion cysts range in size from several millimeters in diameter to bulky masses that may fill the pelvis and abdomen. The development of a peritoneal inclusion cyst depends on the presence of an active ovary and peritoneal adhesions.

# Diagnosis
The normal peritoneum absorbs fluid easily. However, when the peritoneum is injured, there is a decrease in the clearance of ovarian fluid. Peritoneal inclusion cysts have no malignant potential despite the occasional occurrence of metaplasia. Most patients with peritoneal inclusion cysts present with pelvic pain or a pelvic mass.
- T2
- T2
- T2

# Treatment
- Conservative treatment (use of oral contraceptives to suppress ovulation, pain medication) is the first line of treatment.
- Surgical resection of adhesions is necessary only in selected cases. After surgical resection, the risk of recurrence is 30-50%.
Phaeodactylum tricornutum
Phaeodactylum tricornutum is a diatom. It is the only species in the genus Phaeodactylum.

# Gene Sequencing
Phaeodactylum tricornutum is one of two diatoms to have its genome sequenced (the other being Thalassiosira pseudonana). Over 30000 expressed sequence tags (ESTs) have been organized into the Diatom EST Database.

# Distribution
Phaeodactylum ranges from France and Germany in Europe to Novia Scotia in North America.
Phlegmasia cerulea dolens

# Overview
Phlegmasia cerulea dolens is a rare but severe form of deep venous thrombosis which results from extensive thrombotic occlusion of the major extremity veins and their collaterals.

# Pathogenesis
Phlegmasia cerulea dolens is characterized by sudden severe pain, swelling, cyanosis and edema of the affected limb. Cyanosis is pathognomic for Phlegmasia cerulea dolens. It is a a part of spectrum of changes associated with underlying deep vein thrombos.
- DVT results in occlusion of the vasculature, thus hindering the normal drainage of deoxygenated blood to the heart.
- Based on the duration, burden of clot and vascular morphology the overlying skin may appear normal or have whitish or bluish discoloration.
- Whitish discoloration of skin secondary to an underlying DVT, compromising arterial supply and thus resulting in sequestration of fluid, this is referred as Phlegmasia alba dolens.
- If not addressed promptly, Phlegmasia alba dolens can progress to complete obstruction of collateral, resulting in venous congestion and bluish discoloration (cyanosis), referred as Phlegmasia cerulea dolens.
There is a high risk of massive pulmonary embolism, even under anticoagulation. Foot gangrene may occur and is often followed by circulatory collapse and shock. Delay in treatment can be fatal or can lead to loss of limb.

# Treatment options
- Phlegmasia cerulea dolens is the only indication of thrombolysis or thrombectomy in patients with deep vein thrombosis.
- Initiation of heparin followed by assessment for further management with thrombolysis or thrombectomy is done based on clinical presentation.
- Use of IVC filter is based on physician preference and a consensus does not yet exist on its use.
- For further details visit Deep vein thrombosis
Phytanoyl-CoA dioxygenase
In enzymology, a phytanoyl-CoA dioxygenase (EC 1.14.11.18) is an enzyme that catalyzes the chemical reaction
File:Alpha oxidation part II.svg
The three substrates of this enzyme are phytanoyl-CoA, 2-oxoglutarate (2OG), and O2, whereas its three products are 2-hydroxyphytanoyl-CoA, succinate, and CO2.
This enzyme belongs to the family of iron(II)-dependent oxygenases, which typically incorporate one atom of dioxygen into the substrate and one atom into the succinate carboxylate group. The mechanism is complex, but is believed to involve ordered binding of 2-oxoglutarate to the iron(II) containing enzyme followed by substrate. Binding of substrate causes displacement of a water molecule from the iron(II) cofactor, leaving a vacant coordination position to which dioxygen binds. A rearrangement occurs to form a high energy iron-oxygen species (which is generally thought to be an iron(IV)=O species) that performs the actual oxidation reaction.

# Nomenclature
The systematic name of this enzyme class is phytanoyl-CoA, 2-oxoglutarate:oxygen oxidoreductase (2-hydroxylating). This enzyme is also called phytanoyl-CoA hydroxylase.

# Examples
In humans, phytanoyl-CoA hydroxylase is encoded by the PHYH (aka PAHX) gene and is required for the alpha-oxidation of branched chain fatty acids (e.g. phytanic acid) in peroxisomes. PHYH deficiency results in the accumulation of large tissue stores of phytanic acid and is the major cause of Refsum disease.

# Related enzymes
Iron(II) and 2OG-dependent oxygenases are common in microorganisms, plants, and animals; the human genome is predicted to contain about 80 examples, and the model plant Arabidopsis thaliana likely contains more. In plants and microorganisms this enzyme family is associated with a large diversity of oxidative reactions.
Pityriasis rosea overview

# Overview
Pityriasis rosea is a skin disease marked by patches of pink, oval rash.  Although its exact cause is unknown and its onset is not linked to food, medicines or stress, it is thought that this essentially non-contagious condition is set off by a virus.  Pityriasis rosea can affect members of either sex of any age. However, it is most common in females and those between the ages of 8 and 35.  Symptoms only recur in 3% of the affected.

# Risk Factors
Although pityriasis rosea may occur in more than one person in a household at a time, it is not thought to spread from one person to another.

# Natural History, Complications and Prognosis
Pityriasis rosea usually lasts between 8 to 10 weeks  the rashes disappear without scarring.  In people with dark complexions, however, hyperpigmented discolorations may last for several months afterwards.
Although Pityriasis rosea may occur in more than one person in a household at a time, it is not thought to be highly contagious.
Dogs and bears are known to be afflicted by Pityriasis rosea quite frequently
Pneumonic plague overview

# Overview
Pneumonic plague, a severe type of lung infection, is one of three main forms of plague, all of which are caused by the bacterium Yersinia pestis. It is more virulent and rare than bubonic plague. The difference between the versions of plague is simply the location of the infection in the body; the bubonic plague is an infection of the lymphatic system, the pneumonic plague is an infection of the respiratory system, and the septicemic plague is an infection in the blood stream.

# Pathophysiology
Pneumonic plague can be caused in two ways: primary, which results from the inhalation of aerosolised plague bacteria, or secondary, when septicemic plague spreads into lung tissue from the bloodstream. Pneumonic plague is not exclusively vector-borne like bubonic plague; instead it can be spread from person to person. There have been cases of pneumonic plague resulting from the dissection or handling of contaminated animal tissue. This is one type of the formerly known Black Death.  It could kill 90%95% of a population if the victims coughed and passed on the bacteria.

# Epidemiology and Demographics
Since 2002, the World Health Organization (WHO) has reported seven plague outbreaks, though some may go unreported because they often happen in remote areas. Between 1998 and 2009, nearly 24,000 cases have been reported, including about 2,000 deaths, in Africa, Asia, the Americas and Eastern Europe. 98 percent of the world's cases occur in Africa.

# Natural History, Complications and Prognosis
The pneumonia progresses for two to four days and may cause respiratory failure and shock. Patients will die without early treatment, some within 36 hours.  Pneumonic plague is a very aggressive infection requiring early treatment.  The mortality rate from untreated pneumonic plague approaches 100%.

# Treatment

## Medical Therapy
Antibiotics must be given within 24 hours of first symptoms to reduce the risk of death. Streptomycin, gentamicin, tetracyclines, and chloramphenicol are all effective against pneumonic plague.  Antibiotic treatment for 7 days will protect people who have had direct, close contact with infected patients. Wearing a close-fitting surgical mask also protects against infection.

## Future and Investigational Therapies
The main investigational technique being looked into is that of a vaccine to stop any possible plague outbreaks. Currently, there is not an available vaccine against the plague, particularly the pneumonic version. This all may be changing because there has been research conducted giving promising results for a vaccine against the pneumonic plague.
Porphobilinogen deaminase
Porphobilinogen deaminase (hydroxymethylbilane synthase, or uroporphyrinogen I synthase) is an enzyme (EC 2.5.1.61) that in humans is encoded by the HMBS gene. Porphobilinogen deaminase is involved in the third step of the heme biosynthetic pathway. It catalyzes the head to tail condensation of four porphobilinogen molecules into the linear hydroxymethylbilane while releasing four ammonia molecules:

# Structure and function
Functionally, porphobilinogen deaminase catalyzes the loss of ammonia from the porphobilinogen monomer (deamination) and its subsequent polymerization to a linear tetrapyrrole, which is released as hydroxymethylbilane:
The structure of 40-42 kDa porphobilinogen deaminase, which is highly conserved amongst organisms, consists of three domains.  Domains 1 and 2 are structurally very similar: each consisting of five beta-sheets and three alpha helices in humans. Domain 3 is positioned between the other two and has a flattened beta-sheet geometry.  A dipyrrole, a cofactor of this enzyme consisting of two condensed porphobilinogen molecules, is covalently attached to domain 3 and extends into the active site, the cleft between domains 1 and 2.  Several positively charged arginine residues, positioned to face the active site from domains 1 and 2, have been shown to stabilize the carboxylate functionalities on the incoming porphobilinogen as well as the growing pyrrole chain.  These structural features presumably favor the formation of the final hydroxymethylbilane product.  Porphobilinogen deaminase usually exists in dimer units in the cytoplasm of the cell.

# Reaction mechanism
The first step is believed to involve an E1 elimination of ammonia from porphobilinogen, generating a carbocation intermediate (1).  This intermediate is then attacked by the dipyrrole cofactor of porphobilinogen deaminase, which after losing a proton yields a trimer covalently bound to the enzyme (2).  This intermediate is then open to further reaction with porphobilinogen (1 and 2 repeated three more times).  Once a hexamer is formed, hydrolysis allows hydroxymethylbilane to be released, as well as cofactor regeneration (3).

# Pathology
The most well-known health issue involving porphobilinogen deaminase is acute intermittent porphyria, an autosomal dominant genetic disorder where insufficient hydroxymethylbilane is produced, leading to a build-up of porphobilinogen in the cytoplasm.  This is caused by a gene mutation that, in 90% of cases, causes decreased amounts of enzyme.  However, mutations where less-active enzymes and/or different isoforms have been described.
Posaconazole how supplied

# How Supplied/Storage And HandlinG

### Delayed-Release Tablets
Noxafil 100 mg delayed-release tablets; yellow, coated, oblong, debossed with "100" on one side. Bottles with child-resistant closures of 60 delayed-release tablets (NDC 0085-4324-02). Store at 20-25C (68-77F), excursions permitted to 15-30C (59-86F) .

### Oral Suspension
Noxafil oral suspension is available in 4-ounce (123 mL) amber glass bottles with child-resistant closures (NDC 0085-1328-01) containing 105 mL of suspension (40 mg of posaconazole per mL).
Supplied with each oral suspension bottle is a plastic dosing spoon calibrated for measuring 2.5-mL and 5-mL doses. Store at 25C (77F); excursions permitted to 15-30C (59-86F) . DO NOT FREEZE.