Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs.
The disease can be either localized to the skin or involve other organs in addition to the skin.
Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs.
The disease can be either localized to the skin or involve other organs in addition to the skin.
Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. Definition; It is a chronic autoimmune disease condition of unknown
etiology characterized by increased
• fibroblast activity and fibrosis in a number of different organ
systems in the form of hardened,
• sclerotic skin and other connective tissues.
• It is 4 times more common in females.
There are three patterns of disease:
• 1) Limited cutaneous systemic sclerosis:
• Raynaud's may be first sign
• Scleroderma affects face and distal limbs predominately
• Associated with anti-centromere antibodies
• CREST syndrome is an older term for the limited cutaneous form.
• CREST syndrome is a subtype of limited cutaneous systemic
sclerosis: Calcinosis, Raynaud's
• phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
3. Complications of CREST syndrome:
Malabsorption can develop in these patients secondary
to bacterial overgrowth of the sclerosed
• small intestine (dysmotility secondary to infiltration of
the intestinal wall with fibrous tissue).
• Also, unfortunately pulmonary hypertension is one of
the more common late complications seen
• in such patients.
• It is often difficult to distinguish between interstitial
lung disease and pulmonary hypertension as the
• cause of breathlessness in systemic sclerosis
4. • NB: Lung involvement is a frequent complication of systemic
sclerosis, and can be split into 2 main
• syndromes:
• 1- pulmonary vascular disorder evolving over time into relatively
isolated pulmonary
• hypertension
• 2- interstitial lung disease.
• 2) Diffuse cutaneous systemic sclerosis
• Scleroderma affects trunk and proximal limbs predominately
• Associated with scl-70 antibodies
• Hypertension, lung fibrosis and renal involvement seen
• Poor prognosis
• Whilst diffuse systemic sclerosis is associated with more severe and
rapid internal organ
• involvement it is also seen in the limited form.
5. • 3) Morphea (Localized Scleroderma) (without internal
organ involvement)
• tightening and fibrosis of skin
• May be manifest as plaques (morphoea) or linear.
• This is a well-defined oval to round plaque. (Like a painless
lesion to his left subcostal region,
• dry, indurated and slightly coarse to palpation).
• The pathogenesis is poorly defined.
• An autoimmune component is suggested by enhanced T
helper 2 (Th2) dependent interleukin 4
• (IL-4) activity, which in turn up regulates transforming
growth factor beta (TGF -beta). TGF-beta
• stimulates fibroblast production of collagen and other
extracellular matrix proteins.
6. Presentation:
• Typical patient is a young female (35-65); Male: female ratio of about 1:4; Prevalence about 10-20
per 100000
• in the population
• Onset: Initial symptoms are typically non-specific and include Raynaud’s phenomenon, fatigue, and
• musculoskeletal complaints.
• The first specific clue is skin thickening that begins as swelling or puffiness of the fingers and hands.
• The patient feels a progressive tightening of the skin and decreased flexibility.
• In diffuse SSC various degrees of hypo or hyper pigmentation may occur giving the skin a tanned or
• “salt and pepper” appearance.
• Limited SSc (L-SSc): Usually have RP for 1-10 years prior to onset; skin involvement is distal to the
• elbows and knees but may involve the face.
• Diffuse SSc (d-SSc): Short interval between onset of RP and skin involvement which includes the
trunk
• & extremities
7. Progression:
• As SSc progresses the skin becomes progressively tighter and
thicker. This stage may persist for one to
• three years, after which the skin tends to soften and either thins
(becomes atrophic and thinned, with
• tethering to underlying structures) or returns toward normal
texture. After this initial improvement
• the disease may be progressive.
• Constitutional Features: Fatigue may be prominent, weight loss due
to activity of the disease and GI
• involvement with anorexia.
• Functional Status: Reduced functional status with difficulties with
ADLs; Difficulty at work; Loss of
• libido - Erectile dysfunction in men is common; Depression in up to
50%
8. Review of systems:
• Vascular: Raynaud’s Phenomenon (RP): Present in 95% of patients with SSc vs 4%
of general
• population; In SSC, RP is associated with tissue fibrosis of the fingers, loss of the
digital pads, digital
• ulceration, and on occasion digital ischemia with amputation
• Musculoskeletal: Arthralgias and myalgias are one of the earliest symptoms; A
rheumatoid-like
• erosive polyarthritis is occasionally seen (<20%); Inflammation and fibrosis of the
tendon sheaths also
• lead to pain and restriction of movement with accompanying tendon friction rubs;
Muscle weakness
• and atrophy is a dominant problem in late SSc secondary to fibrosis, disuse,
contractures of fibrotic
• skin, along with malnutrition
• Mucocutaneous: Xerostomia and xerophthalmia
• Neurologic: Trigeminal neuralgia; Other entrapment neuropathies such as carpal
tunnel
• Cardiac: Pericardial effusions; Myocardial fibrosis with diastolic dysfunction;
Premature coronary
• artery disease
9. • Respiratory: Leading cause of mortality in SSc;
• (a) Interstitial Fibrosis: Occurs with diffuse disease (30-60%), anti-topoisomerase-1
antibodies (Scl-70),
• and FVC<75 early in the course of disease;
• (b) Pulmonary hypertension without fibrosis occurs in 20-25% of limited SSc
patients and less often in
• diffuse disease: Risk factors include long standing RP and limited SSc; Poor survival
- 90% were dead at
• 5 years; Pulmonary arterial pressures (PAP) >45 with right sided heart changes
correlate with
• catheterization in 90% of cases. Right heart catheterization should be done in all
cases to confirm the
• diagnosis.
• Gastrointestinal: Small oral aperture; Dental disease and oral sicca features;
Esophageal dysmotility
• with resulting GERD; Gastric ectasia (watermelon stomach); Pseudo obstruction
secondary to small
10. .
• Respiratory: Leading cause of mortality in SSc;
• (a) Interstitial Fibrosis: Occurs with diffuse disease (30-60%), anti-
topoisomerase-1 antibodies (Scl-70),
• and FVC<75 early in the course of disease;
• (b) Pulmonary hypertension without fibrosis occurs in 20-25% of limited
SSc patients and less often in
• diffuse disease: Risk factors include long standing RP and limited SSc; Poor
survival - 90% were dead at
• 5 years; Pulmonary arterial pressures (PAP) >45 with right sided heart
changes correlate with
• catheterization in 90% of cases. Right heart catheterization should be
done in all cases to confirm the
• diagnosis.
• Gastrointestinal: Small oral aperture; Dental disease and oral sicca
features; Esophageal dysmotility
• with resulting GERD; Gastric ectasia (watermelon stomach); Pseudo
obstruction secondary to small
• Renal : one of the main causes of death is hypertensive renal crisis ,
characterized by rapidly developing accelerated phase hypertension and
renal failure , much more likely to occur in DCSSCL
11. INVESTIGATIONS:
CBC: Thrombocytopenia and microangiopathic hemolysis (schistocytes) with
renal crisis.
• Urinalysis: Proteinuria with renal crisis
• Creatinine: May be elevated with renal crisis
• Elevated AST/ALT/ALP: Think PBC associated with L-SSc
• ANA: In majority of cases
• Anti-Topoisomerase-1 (Scl-70): Diffuse SSc associated with interstitial
pulmonary fibrosis
• Anti-centromere antibodies: Limited SSc
• Anti-Polymerase-III: Diffuse SSc associated with cardiac or renal disease
• Radiology: Soft-tissue calcification; Usually a non-erosive arthritis with
deformities secondary to
contraction of the overlying skin; Reported cases of erosive arthritis
Screening (yearly): Chest radiographs; ECG & echocardiogram; Pulmonary
function test
13. management:
• Disease Modifying Interventions: Methotrexate -
Possible favorable outcome in skin; D-Penicillamine,
chlorambucil, and interferon-alpha have not been
fruitful
• Treatment of Skin Disease: Topical moisturizers; Treat
ulcers with anti-septic, antibiotic ointments,
and analgesics; Calcinosis - Can try colchicine
• Raynaud’s Phenomenon: Avoid cold and keep warm
(socks, hat, scarf, gloves); Stop smoking; Avoid
estrogen containing compounds; Calcium channel
blockers; Topical nitroglycerin paste; IV iloprost
14. .
• Gastrointestinal: Reduce caffeine and alcohol, stop
smoking, elevate head of the bed, avoid foods
which precipitate GERD, eat frequent small meals; Oral
antacids, H2 blockers, and proton pump
inhibitors; Metoclopromide, erythromycin, or
domperidone for dysmotility; Broad spectrum
antibiotics; Supplemental vitamins
• Cardiopulmonary: cyclophosphamide is effective in
slowing progression of interstitial lung disease and
similar result observed with MMF. More recently the
tyrosine kinase inhibitor nintedanib ( 150mg twice
daily has shown efficacy in slowing decline of lung
function in DCSSCL
15. Scleroderma Renal Crisis management:
• Control blood pressure: Discontinue any medications which may
worsen blood pressure; ACEInhibitors - Have improved survival
from 10% in 1 year to 90% in 5 years. Captopril is most commonly
used aiming to reduce blood pressure slowly. Dose 25 mg PO BID-
TID increasing to max 150 mg TID; Angiotensin receptor blockers -
Less effective than ACE (? Lack of bradykinin effect; Calcium channel
blockers; Dialysis and renal care; Consult nephrology; Continue ACE
during dialysis as persistent hyperreninemia may occur; Supportive
• Treatment: Consult cardiology if CHF is an issue; Oxygen; Careful
use of diuretics; Nitrates; Statins; Neurology involvement if
associated encephalopathy or seizures; Correct electrolyte
abnormalities
• Musculoskeletal: Physiotherapy - Early and aggressive to prevent
joint contractures; Acetaminophen; NSAIDs and COXIBs;
Methotrexate and corticosteroids for inflammatory myopathies
16. Poor Prognosis:
• Older age
• Diffuse skin disease
• Proteinurea
• High ESR
• Low gas transfer factor for carbon monoxide
• Pulmonary hypertension