Science: "Unlock Even More Possibilities with Single Cell Sequencing" core facility technology meeting

 Yesterday (8/11/22), our research core facility and "new" technology vendors (incl. 10X genomics, illumina) were setting up a 4-hour symposium, titled "Unlock Even More Possibilities with Single Cell Sequencing". 

These "new" technologies are combining sequencing and imaging (called "multi-omics with imaging"), providing us users a lot more data and information that were not obtainable before.

There are a few companies competing for this "multi-omics with imaging" niche. For researchers, "available options" in hand tend to prevail or get used. But it is helpful for us to know strengths and shortcomings of different technologies, companies, and platforms. 

From the standpoint of PI (Principal Investigator) or technology user, our initial questions for new technologies are actually quite simple, including;

   What can they do

   What question/hypothesis can they help us to answer

   Will they be advantageous in obtaining grants and writing a paper

   How much do they cost

   How much do I need to budget

   How much preparation, manpower or trouble to use them

   How much help can I get from the core and vendor to effectively use them

Guess these are quite simple "what's in it for me and for my science" questions and practical questions on implementation.

PIs' have different levels of liking for new technologies. Some are more innovator or early adaptor, others may be more like late majority. 

But, as science is "show and tell", in most cases "just do it" is the best approach.

I've used some new technologies, and also have wanted to use other new technologies. The thing is, the new assays may not come with great support for new users (they fix things while flying) and are usually expensive. 

When one experiment costs 10k+ dollars, we need to think seriously about the return/outcomes and actively look for the money. Although the outcomes would almost be guaranteed to be published or be useful in some ways, $10k+ is not cheap.

So I listened to the symposium. Presenters are from different corners of medical biology, but all were using the single cell sequencing technology. 

The differences in interests were intriguing. But what a technology can do is basically the same. I saw essentially the same kind of presentation over and over. Guess this experience did help me to familiarize myself to the technology.

As technologies advance fast, sometimes it is our understanding that lags behind. Big data reading and interpretation will be increasingly important in the near future.

Will software and AI cover us scientists (or even replace us)? For description and identification segments, it is likely. But we still have a room to contribute in interpretation-hypothesizing-testing segments.

How will the technologies evolve in next 10, 20 or 30 years, I wonder during the meeting. It is good to have time to think about future science.

Science: AAIC (Alzheimer's Association International Conference) 2022 (7/31-8/4/2022)

 Some years ago, a part of my research branched out from cancer to Alzheimer's disease. Last year I wrote a grant to fund the Alzheimer's disease related study. The "big" grant was not funded, but scored, which led to a small grant that allows us to "fix" the big grant and resubmit it.

So the Alzheimer's-related project continued. To familiarize myself to the broader Alzheimer's disease research field, I budgeted to attend AAIC 2022 conference in the small grant.

The AAIC is a major research conference for Alzheimer's disease research. Over years I've attended different meetings from different organizations; Cancer Research (ACS, AACR), Cell Biology, Molecular Biology, Yeast biology, Cell Cycle conference, and so on. They came with different flavors and had different cultures. I was curious about the AAIC and Alzheimer's disease research.

Due to some delays in analysis with expensive new technology (we do not get a hang of it until we actually do it, don't we), we did not get to present results in the AAIC22 conference. Well, that is okay. We will know the results in a few weeks.

Anyhow, I signed up for the AAIC 2022 meeting online/virtual. The meeting itself was hybrid, offering actual meeting in San Diego with an option to watch symposiums and posters online.

To be honest, in covid time I've come to like virtual conference. Apparently I am not very fond of business travels. I am fine with attending sessions while sipping tea in my office. Virtual meeting cost much less, too ($250 to be exact).

The sessions were quite interesting. There were a lot of talks on immunological aspects in Alzheimer's disease development. Disease disparity (e.g., racial differences in clinical trials) appeared to be a hot topic.

Yet, the conference gave me an impression that how incomplete our understanding on Alzheimer's disease still is.

I may be speaking from the standard of cancer research, where the major frames of understanding seem to have been already established, much better than those for Alzheimer's.

In other words, there is still so much work to do in Alzheimer's disease research field.

For example, for cancers, personalized medicine approach has increasingly become common. Clinician colleagues discuss treatment strategy based on test results of genomic mutations from each patient's cancer.

In AAIC22, there were talks about different types of Alzheimer's. But molecular signatures for each type are vague, and treatments for the different types are yet to be elucidated.

As our methodologies are rapidly advancing and clinical/disease data keep piling up, I'd imagine, 10-20 years from now, AAIC would look quite different. They may be talking about Alzheimer's disease subtypes and causes, and treatment or prevention options for each subtype. Current therapies of 2022 would be obsolete and things of the past.

As a "newcomer", I do not have much emotional investment in current treatment strategies. I am fine if current treatments become obsolete. They have not shown great efficacies anyway.

Clearly there are unmet needs in current medical practices in Alzheimer's disease. 

How can we address them?

Bottom line. We do not have effective therapies for Alzheimer's disease as of 2022. That makes now an interesting time for scientists.

[AAIC22 virtual conference landing page, boasting nearly 9,000 attendants]

Dance: Wild Wild Westie (W3) 2022; brief introduction to WCS events; raw energy of social dance

 Wild Wild Westie (W3) is a West Coast Swing (WCS) event in Dallas, held on July 4th weekend since 2012.

Holding a national-level dance event is a lot of work for organizers; inviting traveling pros as judges and/or as performers/teachers/MCs/DJs, booking hotel with big dance floor(s), mobilizing not a small number of volunteer staff, and above all, needing to attract dancers, so that the event can go on financially. 

In Texas in 2000's, there were big WCS events like Americas Classic in Houston (January) and Dallas Dance in Dallas (Labor Day). They both went belly up in 2010's. No jinxing. 

The W3 basically replaced those events in 2010's, along with Novice Invitational in March.

In 2020-2021, covid shut down all dance events. West Coast Swing communities in this region also took hit from covid. Currently in mid 2022, WCS communities are more or less in recovery phase. 

I had not been to big (3+ days) WCS event for a long time.  As life threat of covid is reduced with vaccination and improvements in other treatments, I felt like going to a big WCS event. I love this dance after all. So I made this July 4th weekend a mini dance vacation. 

I left OKC on Saturday, drove 4 hours, got tested for covid (this event is a covid testing event with vaccine requirement), joined the event in the evening for watching competitions/shows and late night social dance. I spent Sunday for the same, then came back on Monday July 4th. Glad to see familiar faces and to meet new people.

What you see in WCS event:

Big WCS events are usually structured like this; they have leveled competitions for novice (meaning WCS competition novice, not total beginners), intermediate/advanced, and champions. These categories are defined by points each dancer accumulates in WCS contests. Winning/higher placements gives you more points at a time. Levels are aligned from amateur contests to more interesting/show-worthy contests. 

The point system is not exactly the ideal system, as it assumes dancers' current levels are proportional to points (it is not. But it may make sense to encourage personal engagement and growth). As such, point system can work as a barrier to established dancers like professional dancers in other dances. But a better system is hard to find.  

To some, WCS points are brownie points. To others, the points are tangible awards for their efforts, sum of good memories, and/or something that may come with perks. 

If you are committing to WCS contests, read the rules, practice the dance and sign up.

I digress. Competition categories include Jack and Jill, Strictly Swing, Pro-Am, and Routine ("Classic" and "Showcase" defined by lifts/drops/non-swing dance moves allowance). They are also categorized by dancers ages, from junior to sophisticated (age 35+) and masters (+50).

In addition, there are workshops and classes. They can teach many subjects; patterns, drills, contest mindsets, choreographed moves, connection, etc.

And social dances in between the contests and in late night. This social dance hours are for all, both for active contestants and for "just dance and have fun" people, who may or may not be former contestants or otherwise very good dancers. 

Good thing about social dance is that people don't care about titles. Sure, the way they dance gives away who are (likely) pros and who are not. But asking dance is a lot simpler in WCS than, say, Cabeceo ritual of Tango.

Now, a note on dance levels. I am talking from a spectator's standpoint here.

Some dances are clearly divided to (a) stage dance by pros and to (b) dance by amateurs, like ballet, jazz/contemporary, and ballroom. Pro performers in these dances are (or they better be), convincingly professional performers, even to layman's eyes. These stage dancers with "trained" look make Broadway shows and National TV-level stage shows.

Argentine Tango and WCS were born from social dance. In 110+ years of history, AT went through this pro/am separation. Someone in a book "Tango Tips" described stage AT performance as "professional deformation". I laughed, but true, what pros do on stage shows is so far apart from the hug and walk, what social Tango dancers do on social dance floor.

WCS is younger and is still going through this pro-am separation. Some (few) dancers are polished to the level of Broadway shows. Most are not.

"Most are not", but in general, followers (usually women) are better dancers in WCS, same with Argentine Tango. 

Perhaps it is due to the differences in the lead/follow roles. Leaders' primary job is support, then lead, then dance and look good, in this order. Refining dances and becoming appealing dancers are late in the agenda for leaders. Alpha-male type dancer-leader are rare and far in between.

Followers' primary job is to "follow and dance and look good", at the same time. In contests, they hardly survive without some form of appeal. They are better, because the selection is tougher? Maybe.

As followers are better dancers, it can show in the dance. Sometimes it looks like "one-woman show", when follower being strong dancer and the lead focusing on his support role. Each couple, especially leader, needs to think how they can create nice dance. 

Note on Lead and Follow roles:

Which is tougher, follow or lead? It is up to you to decide. And you can literally decide after you try them both. In the W3, there were lots of dancers with "switch roles", and even a class for that. I usually lead, but can follow and dance. I can tell you, following is lots of physical work, as the main "moving parts" is the follower in WCS. 

After all, WCS is a swing dance, and swing motion has both slow and fast aspects. WCS dancers usually use "slow" time for anchor and play, and use "fast" time for smooth moving to create the mix of slow/fast (swing) motions. Leader tends to stay in the middle playing the role of support and visual center point, and follower moves around like the swinging seat.

Speaking of physical work, in fact, you can see much faster speed of energy flow in higher level WCS dancers than, say, novice and masters. Having quick feet and fast response time is an indicator as advanced (or younger) WCS dancers. There is no immediate cure to fix immobile or all slow follower in WCS. Overall smoothness and the swing motion cannot be achieved without both partners bringing knowledge and physical ability to the dance floor. 

On social dance:

I did late night dance for two nights (seriously, after such a long time). I do not always like late night dance, because in late night dance people tend to lose concentration and go to autopilot mode. Crèche moves with overactive frame can be the norm.

But the late night dance floor was filled with raw energy. After these years including covid. What fun it was.

I did lots of watching as well. The social dance may not always look polished. But who cares. Something interesting is coming out of all these energy and experiments. WCS is alive and well there. I love it.

I hope WCS communities come back from covid disruption soon, safe and sound.

PS  Covid variant is on the rise again and there were reports of tested-positive at the event. They went to immediate quarantine and masking. I checked myself yesterday and was negative. We'd have to deal with covid like this for some time.

Science: "Cancer disappeared!" news on early June 2022 (cancer journal club in the lab)

 A few weeks ago, many major news outlets reported this news, sensationally titled "cancer disappeared!".

The news was based on a report on New England Journal of Medicine (NEJM), published on 6/5/2022. The journal is highly regarded.

Link to the paper.  https://www.nejm.org/doi/10.1056/NEJMoa2201445

We picked up the paper for our journal club in the lab.

Background. 

(a) Immunotherapy reagent (PD1 blocker) has shown success in various cancers, including metastatic (stage 4) colorectal cancer. 

(b) PD1 blocker indicated particularly good efficacy on a subset of cancers with mismatch-repair deficient characteristic.

(c) Standard colorectal cancer therapy is initial treatment with chemotherapy drugs (combination of DNA damaging drugs such as fluoropyrimidine and platinum compound oxaliplatin), followed by chemoradio therapy then surgery. 

(d) But the response rate for the standard therapy is up to 25%. The current therapy comes with complications, toxicity and fertility challenge. Much to be desired.

In the report, the group in Sloan Kettering Memorial Cancer Center hypothesized that single reagent PD1 blocker could be effective in patients with mismatch-repair deficient, localized (stage 2 and 3) rectal cancers.

They enrolled 16 patients with mismatch repair-deficient rectal cancer and stated treatment with PD1 blocker every 3 weeks for 6 months.

 In the planning, (Plan A) if the single drug treatment work, no chemo or surgery, and (Plan B) the PD1 blocker treatment should be followed by chemoradiotherapy then surgery (=standard therapy).

They monitored the cancer at the start, 6 weeks, 3 months and 6 months. 

Amazingly, the cancer literally "disappeared" in 100% of 12 patients who went through the 6 months treatment of PD1 blocker. 

In all clinical monitoring parameters (imaging analyses with MRI, PET, endoscopy, digital examination, histopathological analyses on biopsy samples), rectal cancers were not seen. They did not even have to pull out the Plan B/follow up with chemoradio therapy then surgery.

If we point out something cautionary and less rosy, 

(i) mismatch repair-deficient colorectal cancers are about 5-10% of colorectal cancers. 

(ii) This is a phase2 trial with small size of white patients in single institute. 

(iii) If the cancer ever comes back or not in a long term remains to be seen.

(iv) They did not talk about the cost, but PD1 blockers are not cheap. 

Yet, the way cancer disappeared with only mild to moderate side effects if any was indeed newsworthy.

Cancer is a collection of many diseases. They reported a very effective way to deal with mismatch repair-deficient, stage 2/3 rectal cancers. Highly promising.

Cancer is "cured" like this. You can call it a trench warfare. By conquering one type of cancer at a time, we'd eventually have effective ways to "cure" many other types of cancers.

[For non-medical practitioners. gross alert]

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[Figure 1A from the paper. An example of "cancer disappearance" over time]