Persius/hicric huggingface dataset:
Visceral leishmaniasis overview

# Overview
Visceral leishmaniasis (VL) is the most severe form of leishmaniasis, a disease caused by parasites of the Leishmania genus.  It is the second-largest parasitic killer in the world (after malaria), responsible for an estimated 60 000 who die from the disease each year out of half-million infections worldwide.  The parasite migrates to the visceral organs such as liver, spleen and bone marrow and if left untreated will almost always result in the death of the mammalian host. Signs and symptoms include fever, weight loss, anemia and substantial swelling of the liver and spleen.  Of particular concern, according to the World Health Organization (WHO), is the emerging problem of HIV/VL co-infection.

# Causes
Several species of Leishmania are known to give rise to the visceral form of the disease.  The "Old World" (Africa, Asia, Europe) species are L. donovani and L. infantum and the "New World" (South America) species is L. chagasi.

# Diagnosis

## History and Symptoms
When a human patient does develop visceral leishmaniasis, the most typical symptoms are fever and the enlargement of the spleen, or splenomegaly, with enlargement of the liver - hepatomegaly, sometimes being seen as well.  The blackening of the skin that gave the disease its common name in India does not appear in most strains of the disease, and the other symptoms are very easy to mistake for those of malaria.

## Other Diagnostic Studies
Other tests being developed include a latex agglutination test (KAtex), which is currently being tested in Asia and Africa.  Another potential test detects erythrosalicylic acid.
Vitamin B12 deficiency overview

# Overview
B12 deficiency can potentially cause severe and irreversible damage, especially to the brain and nervous system.
The daily cobalamin (vitamin B12) requirement is  1-2 mcg. An intake of 5-20 mcg/day is usual in a Western diet. The total body can store 2-5 mg. 60% of vitamin B12 is efficiently absorbed via the ileum when it is bound to intrinsic factor (IF).
The first deficiency symptom that was discovered was anemia characterized by enlarged blood corpuscles, so-called megaloblastic anemia.
The anemia is thought to be due to problems in DNA synthesis, specifically in the synthesis of thymine, which is dependent on products of the MTR reaction. Other cell lines such as white blood cells and platelets are often also low.  Bone marrow examination may show megaloblastic hemopoiesis.  The anemia is easy to cure with vitamin B12.
Far more serious is the damage to the nervous system that may occur due to deficiency.

# Historical Perspective

# Classification

# Pathophysiology

# Causes

# Differentiating  from Other Diseases

# Epidemiology and Demographics

# Risk Factors
For vegans, the risk is very high because none of their natural food sources contain B12. One American study found blood levels below normal in 92 % of vegans, 64 % of lacto-vegetarians, and 47% of lacto-ovo vegetarians. The study applied the old normal values, so in reality a considerably greater proportion may have been deficient.

# Screening

# Natural History, Complications, and Prognosis

## Natural History

## Complications

## Prognosis

# Diagnosis

## Diagnostic Criteria

## History and Symptoms

## Physical Examination

## Laboratory Findings

## Imaging Findings

## Other Diagnostic Studies

# Treatment

## Medical Therapy

## Surgery

## Prevention
Vitamin D deficiency prevention

# Overview
Vitamin D is recommended for everyone to prevent vitamin D deficiency. The current guideline by the Institute of Medicine (IOM) recommends 600 IU/d for healthy individuals between 1-70 years of age and 800 IU/d for elderly over 70.

# Prevention
Effective measures for the primary prevention of vitamin D deficiency include dietary intake and cutaneous synthesis. Cutaneous synthesis requires enough sun exposure and it depends on multiple factors including season, latitude, altitude, duration and skin pigmentation. However, there is a concern regarding sun exposure that increases skin cancer. So, it is not recommended to prevent vitamin D deficiency.
- In 2011, the Institute of Medicine (IOM) recommended 600 IU/d of vitamin D for healthy persons over 1 year of age until 70. Recommended Dietary Allowance (RDA) of vitamin D for individuals over 70 years of age is 800 IU/d. RDA for pregnant and lactating women is the same as for nonpregnant adults.
- The National Osteoporosis Foundation (NOF) recommends higer dose 800-1000 IU/d of vitamin D for adults age 50 and older.
- In the UK, the Scientific Advisory Committee on Nutrition (SACN) recommends 400 IU/d of vitamin D (10 micrograms) for everyone above one year of age. Infants, from birth up to one year of age, as a precaution, should consume 340-400 IU/d of vitamin D (8.5-10 micrograms).
- For the Europeans, the European Food Safety Authority (EFSA), published the recommendation as follows:
Infants aged 7-11 months: 10 g/day
For all other population groups aged one year and more (including pregnant/lactating women): 15 g/day
- Infants aged 7-11 months: 10 g/day
- For all other population groups aged one year and more (including pregnant/lactating women): 15 g/day
WD repeat-containing protein 11
WD repeat-containing protein 11 (WDR11) also known as bromodomain and WD repeat-containing protein 2 (BRWD2) is a protein that in humans is encoded by the WDR11 gene.

# Function
This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation.

# Clinical significance
This gene is located in the chromosome 10q25-26 region, which is frequently deleted in gliomas and tumors of other tissues, and is disrupted by the t(10;19) translocation rearrangement in glioblastoma cells. The gene location suggests that it is a candidate gene for the tumor suppressor locus.
Zanamivir clinical pharmacology

# Clinical Pharmacology
Absorption and Bioavailability: Pharmacokinetic studies of orally inhaled zanamivir indicate that approximately 4% to 17% of the inhaled dose is systemically absorbed. The peak serum concentrations ranged from 17 to 142 ng/mL within 1 to 2 hours following a 10 mg dose. The area under the serum concentration versus time curve (AUC) ranged from 111 to 1,364 ngh/mL.
Distribution: Zanamivir has limited plasma protein binding (<10%).
Metabolism: Zanamivir is renally excreted as unchanged drug. No metabolites have been detected in humans.
Elimination: The serum half-life of zanamivir following administration by oral inhalation ranges from 2.5 to 5.1 hours. It is excreted unchanged in the urine with excretion of a single dose completed within 24 hours. Total clearance ranges from 2.5 to 10.9 L/h. Unabsorbed drug is excreted in the feces.
Impaired Hepatic Function: The pharmacokinetics of zanamivir have not been studied in patients with impaired hepatic function.
Impaired Renal Function: After a single intravenous dose of 4 mg or 2 mg of zanamivir in volunteers with mild/moderate or severe renal impairment, respectively, significant decreases in renal clearance (and hence total clearance: normals 5.3 L/h, mild/moderate 2.7 L/h, and severe 0.8 L/h; median values) and significant increases in half-life (normals 3.1 h, mild/moderate 4.7 h, and severe 18.5 h; median values) and systemic exposure were observed. Safety and efficacy have not been documented in the presence of severe renal insufficiency. Due to the low systemic bioavailability of zanamivir following oral inhalation, no dosage adjustments are necessary in patients with renal impairment. However, the potential for drug accumulation should be considered.
Pediatric Patients: The pharmacokinetics of zanamivir were evaluated in pediatric subjects with signs and symptoms of respiratory illness. Sixteen subjects, aged 6 to 12 years, received a single dose of 10 mg zanamivir dry powder via DISKHALER. Five subjects had either undetectable zanamivir serum concentrations or had low drug concentrations (8.32 to 10.38 ng/mL) that were not detectable after 1.5 hours. Eleven subjects had Cmax median values of 43 ng/mL (range: 15 to 74) and AUC median values of 167 ngh/mL (range: 58 to 279). Low or undetectable serum concentrations were related to lack of measurable PIFR in individual subjects .
Geriatric Patients: The pharmacokinetics of zanamivir have not been studied in subjects older than 65 years .
Gender, Race, and Weight: In a population pharmacokinetic analysis in patient trials, no clinically significant differences in serum concentrations and/or pharmacokinetic parameters (V/F, CL/F, ka, AUC0-3, Cmax, Tmax, CLr, and % excreted in urine) were observed when demographic variables (gender, age, race, and weight) and indices of infection (laboratory evidence of infection, overall symptoms, symptoms of upper respiratory illness, and viral titers) were considered. There were no significant correlations between measures of systemic exposure and safety parameters.
Zanamivir indications and usage

# Indications and Usage

## Treatment of Influenza
RELENZA (zanamivir) Inhalation Powder is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients aged 7 years and older who have been symptomatic for no more than 2 days.

## Prophylaxis of Influenza
RELENZA is indicated for prophylaxis of influenza in adults and pediatric patients aged 5 years and older.

## Important Limitations on Use of RELENZA
- RELENZA is not recommended for treatment or prophylaxis of influenza in individuals with underlying airways disease (such as asthma or chronic obstructive pulmonary disease) due to risk of serious bronchospasm .
- RELENZA has not been proven effective for treatment of influenza in individuals with underlying airways disease.*RELENZA has not been proven effective for prophylaxis of influenza in the nursing home setting.
- RELENZA is not a substitute for early influenza vaccination on an annual basis as recommended by the Centers for Disease Control's Immunization Practices Advisory Committee.*Influenza viruses change over time. Emergence of resistance mutations could decrease drug effectiveness. Other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. Prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use RELENZA.*There is no evidence for efficacy of zanamivir in any illness caused by agents other than influenza virus A and B.*Patients should be advised that the use of RELENZA for treatment of influenza has not been shown to reduce the risk of transmission of influenza to others.
Zazam Sheriff Phillips syndrome

# Overview
Zazam Sheriff Phillips syndrome is a rare genetically congenital syndrome. It is associated with the symptoms of Aniridia, ectopia lentis, abnormal upper incisors and mental retardation.
It is believed to be inherited in an autosomal recessive fashion. Not a lot of research has been undertaken of this particular disease so thus far there is no known gene that affects this condition. However it has been hypothesised that the symptoms described are found at a particular gene, though mental retardation is believed to be due to a different genetic cause.
Consanguinuity has been attributed to affect the chances of inheriting this disease.
1998 Klang Valley water crisis
The 1998 Klang Valley water crisis occurred in Malaysia in February 1998 when the three reservoir dams in Klang Valley, Klang Gates Dam, Batu Dam and Semenyih Dam suffered a substantial drop in water level following the El Nino phenomenon. The subsequent water shortage affected almost all the residents in the Klang Valley causing the government to impose water rationing prior to the 1998 Commonwealth Games in Kuala Lumpur.
The shortage was blamed on El Nino despite actual rainfall in the months leading up to February 1998 in Wilayah Persekutuan 
not being very much below average. In fact in November 1997, Empangan Genting Klang (Genting Klang reservoir) had its highest recorded rainfall. Similarly in October 1997 the Kajang station not far from the Semenyih dam had its highest rainfall in record.
3-dehydrosphinganine reductase
3-dehydrosphinganine reductase (EC 1.1.1.102) also known as 3-ketodihydrosphingosine reductase (KDSR) or follicular variant translocation protein 1 (FVT1) is an enzyme that in humans is encoded by the KDSR gene.

# Function
3-dehydrosphinganine reductase catalyzes the chemical reaction:
Thus, the two substrates of this enzyme are sphinganine and NADP+, whereas its 3 products are 3-dehydrosphinganine, NADPH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. This enzyme participates in sphingolipid metabolism.

# Tissue distribution
Follicular lymphoma variant translocation 1 is a secreted protein which is weakly expressed in hematopoietic tissue.

# Clinical significance
FVT1 shows a high rate of transcription in some T cell malignancies and in phytohemagglutinin-stimulated lymphocytes. The proximity of FVT1 to BCL2 suggests that it may participate in the tumoral process.
Methylcrotonyl-CoA carboxylase
Methylcrotonyl CoA carboxylase (MCC) (3-methylcrotonyl CoA carboxylase, methylcrotonoyl-CoA carboxylase) is a biotin-requiring enzyme located in the mitochondria. MCC uses bicarbonate as a carboxyl group source to catalyze the carboxylation of a carbon adjacent to a carbonyl group performing the fourth step in processing leucine, an essential amino acid.

# Structure

## Gene
Human MCC is a biotin dependent mitochondrial enzyme formed by the two subunits MCCC and MCCC, encoded by MCCC1 and MCCC2 respectively. MCCC1 gene has 21 exons and resides on chromosome 3 at q27. MCCC2 gene has 19 exons and resides on chromosome 5 at q12-q13.

## Protein
The enzyme contains  and  subunits. Human MCCC is composed of 725 amino acids which harbor a covalently bound biotin essential for the ATP-dependent carboxylation; MCCC has 563 amino acids that possess carboxyltransferase activity which presumably is essential for binding to 3-methylcrotonyl CoA. The MCC holoenzyme is thought to be a heterododecamer (66) with close structural analogy to propionyl-CoA carboxylase (PCC), another biotin dependent mitochondrial carboxylase.

# Function
During branched-chain amino acid degradation, MCC performs a single step in the breakdown of leucine to eventually yield acetyl CoA and acetoacetate. MCC catalyzes the carboxylation of 3-methylcrotonyl CoA to 3-methylglutaconyl CoA, a critical step for leucine and isovaleric acid catabolism in species including mammals, plants and bacteria. 3-Methylglutaconyl CoA is then hydrated to produce 3-hydroxy-3-methylglutaryl CoA. 3-Hydroxy-3-methylglutaryl CoA is cleaved into two molecules, acetoacetate and acetyl CoA.
Point mutations and deletion events in the genes coding for MCC can lead to MCC deficiency, an inborn error of metabolism which usually presents with vomiting, metabolic acidosis, very low plasma glucose concentration, and very low levels of carnitine in plasma.

# Mechanism
Bicarbonate is activated by the addition of ATP, increasing the reactivity of bicarbonate. Once bicarbonate is activated, the biotin portion of MCC performs nucleophilic attack on the activated bicarbonate to form enzyme-bound carboxybiotin. The carboxybiotin portion of MCC can then undergo nucleophilic attack transferring the carboxyl group to the substrate, 3-methylcrotonyl CoA, to form 3-methylglutaconyl CoA.

# Regulation
MCC is not regulated by small molecules or dietary or hormonal factors.

# Clinical significance
In humans, MCC deficiency is a rare autosomal recessive genetic disorder whose clinical presentations range from benign to profound metabolic acidosis and death in infancy. Defective mutations in either the  or  subunit have been shown to cause the MCC-deficient syndrome. The typical diagnostic test is the elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. Patients with MCC deficiency usually have normal growth and development before the first acute episode, such as convulsions or coma, that usually occurs between the age of 6-months to 3-years.

# Interactions
MCC has been shown to interact with TRI6 in Fusarium graminearum.
Phosphogluconate dehydrogenase
6-Phosphogluconate dehydrogenase (6PGD) is an enzyme in the pentose phosphate pathway. It forms ribulose 5-phosphate from 6-phosphogluconate.
It is an oxidative carboxylase that catalyses the decarboxylating reduction of 6-phosphogluconate into ribulose 5-phosphate in the presence of NADP. This reaction is a component of the hexose mono-phosphate shunt and pentose phosphate pathways (PPP). Prokaryotic and eukaryotic 6PGD are proteins of about 470 amino acids whose sequences are highly conserved. The protein is a homodimer in which the monomers act independently: each contains a large, mainly alpha-helical domain and a smaller beta-alpha-beta domain, containing a mixed parallel and anti-parallel 6-stranded beta sheet. NADP is bound in a cleft in the small domain, the substrate binding in an adjacent pocket.

# Clinical significance
Mutations within the gene coding this enzyme result in 6-phosphogluconate dehydrogenase deficiency, an autosomal hereditary disease affecting the red blood cells.

## As a possible drug target
6PGD is involved in cancer cell metabolism so 6PGD inhibitors have been sought.
7-Dehydrocholesterol reductase
7-Dehydrocholesterol reductase, also known as DHCR7, is a protein that in humans is encoded by the DHCR7 gene.

# Function
The protein encoded by this gene is an enzyme catalyzing the production of cholesterol from 7-Dehydrocholesterol using NADPH.
The DHCR7 gene encodes delta-7-sterol reductase (EC 1.3.1.21), the ultimate enzyme of mammalian sterol biosynthesis that converts 7-dehydrocholesterol (7-DHC) to cholesterol. This enzyme removes the C(7-8) double bond introduced by the sterol delta8-delta7 isomerases. In addition, its role in drug-induced malformations is known: inhibitors of the last step of cholesterol biosynthesis such as AY9944 and BM15766 severely impair brain development.

# Pathology
A deficiency is associated with Smith-Lemli-Opitz syndrome.

# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. 
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Abacavir indications and usage

# Indications and Usage
- ZIAGEN Tablets and Oral Solution, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
- Additional important information on the use of ZIAGEN for treatment of HIV-1 infection:
- ZIAGEN is one of multiple products containing abacavir. Before starting ZIAGEN, review medical history for prior exposure to any abacavir-containing product in order to avoid reintroduction in a patient with a history of hypersensitivity to abacavir.
Abacavir lamivudine zidovudine

# Overview

# Category
Antiretroviral

# US Brand Names
TRIZIVIR

# FDA Package Insert
Description

# Mechanism of Action
Abacavir: Abacavir is a carbocyclic synthetic nucleoside analogue. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3-OH group in the incorporated nucleotide analogue prevents the formation of the 5 to 3 phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.  CBV-TP is a weak inhibitor of cellular DNA polymerases , , and .
Lamivudine: Lamivudine is a synthetic nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. 3TC-TP is a weak inhibitor of cellular DNA polymerases , , and .
Zidovudine: Zidovudine is a synthetic nucleoside analogue. Intracellularly, zidovudine is phosphorylated to its active 5-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). The principal mode of action of ZDV-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. ZDV-TP is a weak inhibitor of the cellular DNA polymerases  and  and has been reported to be incorporated into the DNA of cells in culture.
DNA repair-deficiency disorder

# Overview
An DNA repair-deficiency disorder is a medical condition due to reduced functionality of DNA repair.
It is sometimes considered synonymous with the term accelerated aging disease, which is a genetic disorder in which various tissues, organs or systems of the human body age prematurely. Because the accelerated aging diseases display different aspects of aging, but never every aspect, they are often called segmental progerias by biogerontologists.
This is in contrast to Progeria (Hutchinson-Gilford Progeria syndrome), which affects a broader spectrum of functions.

# Examples
Some of the examples include:
- Bloom syndrome
- Cockayne's syndrome
- Werner syndrome
- Xeroderma pigmentosum
- Trichothiodystrophy

# Debate concerning "accelerated aging"
Some biogerontologists question that such a thing as "accelerated aging" actually exists, at least partly on the grounds that all of the so-called accelerated aging diseases are segmental progerias. Many disease conditions such as diabetes, high blood pressure, etc. are associated with increased mortality. Without reliable biomarkers of aging it is hard to justify the claim that a disease condition represents more than accelerated mortality.
Against this position other biogerontologists argue that premature aging phenotypes are identifiable symptoms associated with mechanisms of molecular damage. The fact that these phenotypes are widely recognized justifies classification of the relevant diseases as "accelerated aging". Such conditions, it is argued, are readily distinguishable from genetic diseases associated with increased mortality, but not associated with an aging phenotype, such as cystic fibrosis and sickle cell anemia. It is further argued that segmental aging phenotype is a natural part of aging insofar as genetic variation leads to some people being more disposed than others to aging-associated diseases such as cancer and Alzheimer's disease.