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Category: biotech/medical

The frequency-dependent effects of primary hand motor cortex stimulation on volitional finger movement

[Brain stimulation] Taquet et al.: “The effect of motor cortex stimulation on finger flexion is frequency dependent.”

We conducted a prospective study in human patients undergoing awake craniotomies to examine whether the effects of cortical stimulation in hand primary motor cortex (M1) can be frequency dependent and inhibitory.

In 11 participants undergoing clinically indicated awake craniotomies, we delivered bursts of 1–333 Hz stimulation during a finger-flexion task. Synchronized electrocorticography (ECoG), finger joint kinematics, electromyography (EMG), and video were recorded.

Inability to flex the index finger during subthreshold stimulation was noted in 3 participants at frequencies 250 Hz when the electrodes were in locations that induced extension of the forefinger at higher amplitudes. Other than these trials, all stimulation events either induced muscle contractions or had no measurable effect.

Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) Immunotherapy: A Promising Breakthrough in Cancer Therapeutics

PD-1/PD-L1 Inhibitors Implications in Common Human Cancers.

Lung cancer: the landscape of lung cancer treatment has been profoundly reshaped by tumor immunotherapy directed at PD-1/PD-L1. Notably, the effectiveness of PD-L1 inhibitors surpasses that of chemotherapy, particularly in advanced non-small cell lung cancer (NSCLC) patients exhibiting elevated PD-L1 levels. This potency is equally evident among patients with previously untreated metastatic squamous NSCLC. Moreover, when considering patients with NSCLC who have undergone prior treatment, a decreased rate of disease progression is more frequently observed in response to PD-1/PD-L1 inhibitors, as opposed to conventional chemotherapy. This observation holds true, particularly for patients with an extensive metastatic burden and an adverse prognosis. In current clinical therapeutics, a strategic alliance between PD-1/PD-L1 immune checkpoint inhibitors and chemotherapeutic agents has emerged as a cornerstone of treatment. This approach attests to the heightened value these inhibitors bring to the therapeutic arsenal. The rapid evolution of anti-PD-1/PD-L1 inhibitors for advanced NSCLC stands as an instrumental factor in enhancing patient outcomes, charting a promising trajectory toward improved prognosis [,]. In a recent study, neoadjuvant PD-1 inhibitor sintilimab was administered to individuals with NSCLC. The outcomes revealed that a notable 40.5% of participants achieved a major pathological response, while a commendable 10.8% realized a complete remission at the pathological level [].

Prostate cancer: currently, PD-1/PD-L1 immune checkpoint inhibitors have ushered substantial clinical advantages for individuals with prostate cancer. A recent study has put forth the notion that synergizing PD-1/PD-L1 checkpoint inhibitors with radiotherapy presents a promising avenue in the management of prostate cancer []. However, it is noteworthy that the impact of PD-L1/PD-1 blockade in the context of prostate cancer appears comparatively muted in contrast to its influence on other cancer types. This discrepancy stems from the diminished immunogenicity characterizing prostate cancers [].

For 74,000 years, one ancient killer quietly dictated where early humans could survive across Africa

Increasing evidence suggests that our species emerged through interactions between populations living in different parts of Africa, rather than from a single birthplace. Until now, however, most explanations for how those populations were distributed across the continent have focused on climate alone. The new research shows that disease—specifically malaria—also played a crucial role.

In a paper published in Science Advances, researchers from the Max Planck Institute of Geoanthropology, the University of Cambridge, and colleagues have investigated whether Plasmodium falciparum-induced malaria shaped human habitat choice between 74,000 and 5,000 years ago, the critical period before humans dispersed widely beyond Africa and before agriculture dramatically altered malaria transmission.

The study shows that malaria, one of humanity’s oldest and most persistent pathogens, influenced habitat choice by pushing human groups away from high-risk environments and separating populations across the landscape. Over tens of thousands of years, this fragmentation shaped how populations met, mixed, and exchanged genes, helping create the population structure seen in humans today. The findings suggest that infectious disease was not simply a challenge early humans faced: it was a fundamental factor shaping the deep history of our species.

Elusive tularemia proteins reveal possible treatment target in rare tick-borne disease

Tularemia is a rare but highly infectious disease caused by Francisella tularensis, a bacterium that can evade immune defenses. Symptoms of infection can include fever, swollen lymph nodes, and—in some cases—pneumonia. What makes the pathogen especially concerning is how little it takes to cause infection—fewer than 10 bacterial cells can be enough. Scientists at Arizona State University have taken a key step toward understanding how this bacterium survives inside the human body. For the first time, the team has isolated and studied a set of proteins that play a central role in infection, revealing a potential weakness that could eventually be targeted with new treatments. The study is published in the journal Biochimica et Biophysica Acta (BBA)–Biomembranes.

The proteins sit within the bacterium’s inner membrane and appear to work together, forming small assemblies that help it persist inside host cells. Until now, researchers had been unable to produce and stabilize these proteins in the lab, leaving a critical part of the pathogen’s biology unexplored. By developing a method to extract and analyze them, the team has opened the door to more detailed structural studies and eventually, new ways to disrupt the infection process.

The work builds on earlier studies of individual proteins, but advances the research by capturing a group of proteins that function together as a system—one that is essential for infection but had remained inaccessible.

Fecal Microbiota Transplant and Multidrug-Resistant Organism Decolonization in Gastrointestinal Disease: A Randomized Clinical Trial

A randomized clinical trial evaluated if fecal microbiota transplant (FMT) is effective in achieving gut decolonization of multidrug-resistant organisms (MDROs) and reducing antimicrobial resistance (AMR) gene abundance in patients with gastrointestinal (GI) diseases.

Among 114 adults, a single FMT session did not significantly increase rates of MDRO decolonization or reduce antimicrobial resistance gene abundance compared to sham intervention. However, FMT was associated with increased bacterial diversity and enrichment with bacteria capable of producing short-chain fatty acids. No significant safety concerns were observed.

These findings indicate that while a single FMT session does not support routine use for MDRO decolonization in GIDisease, microbiome changes warrant further research.

This randomized clinical trial assesses the efficacy of fecal microbiota transplant in causing multidrug-resistant organism decolonization and decreasing antimicrobial resistance genes in patients with gastrointestinal diseases.

Statins May Lower Risk for Intestinal Strictures in Crohn’s Disease

New research indicates that statin use is associated with a significantly lower risk of developing intestinal strictures in patients with Crohn’s disease. The study suggests that the anti-inflammatory and antifibrotic properties of statins may help prevent the structural damage that often leads to surgical intervention.

Use of statins after the diagnosis of Crohn’s disease is associated with a lower risk for intestinal stricture formation than the use of other non-statin drugs.

Catching cancer’s earliest moments: How mutated cells transform their local environment so a tumor can develop

Scientists at Memorial Sloan Kettering Cancer Center (MSK) and their colleagues are shedding new light on a tumor’s earliest moments—revealing how lung cells with cancer-causing mutations recruit accomplices from healthy surrounding tissue to pave the way for a tumor to develop.

This corruption of the local neighborhood—what scientists call the “tumor microenvironment”—begins surprisingly early, as tumors first emerge, according to a study published April 22 in Nature.

The team’s findings show that when this communication with surrounding cells is disrupted, tumors fail to grow.

Protein map of pain triggering sensory neurons

Nociception refers to how our nerves respond to stimuli that trigger pain. Nerves in skin and other peripheral tissues – such as muscles and joints – that detect damaging stimuli are called nociceptors; they relay signals to the brain to initiate pain.

Using an electrophysiological method known as the patch-clamp technique, the team first identified and characterized two nociceptor subtypes – peptidergic and non-peptidergic – in the spinal ganglia of mice. Each of these subtypes respond differently to similar stimuli and may initiate pain of different quality and duration.

The researchers used around 50 neurons of each subtype to generate a specific protein map for each of the two cell types. Deep Visual Proteomics combines mass spectrometry with microscopy, artificial intelligence and robotics. The team have so far mainly used this methodology for proteome analyses of cancer cells. “We have now shown for the first time that it can also be applied to nerve cells,” another co-senior author says.

The team measured more than 6,000 proteins in these 50 neurons. A comparison with existing RNA data revealed that the transcriptome and proteome of the cells differ significantly in some cases – an indication that key functional processes only become visible at the protein level. “We provide a unique molecular map of pain-initiating neurons,” says the author. “It enables the identification of signaling pathways in these cells that have so far remained hidden.”

In an additional step, the authors wanted to understand which proteins sensitize nerve cells, contributing to chronic pain. They isolated both types of nociceptors from mouse dorsal root ganglia and exposed them to a molecule called Nerve Growth Factor (NGF), which is known to trigger chronic pain both animals and humans, such as in arthritis. Using Deep Visual Proteomics, the researchers were able to precisely identify the proteins produced after the cells were exposed to NGF.

“We identified several proteins that were present in higher levels in a subset of nociceptors following treatment with NGF. The higher levels of these proteins could be linked to long term pain associated with inflammation,” says the first author. One of the proteins, an enzyme called B3GNT2, stood out in particular. “When we knocked out the corresponding gene in the cells, the inflammation-induced hyperactivity of nociceptors was reduced. Fewer cells responded to mechanical stimulus,” the author says. In other words, the neurons had become less sensitive and would elicit much less pain. ScienceMission sciencenewshighlights.

Continue reading “Protein map of pain triggering sensory neurons” | >

🌟Technical advance🌟

Martin Prlic & team demonstrate the feasibility of the FDA-approved blood lancet Tasso+ as an at home blood collection device for remote immune monitoring by high parameter FlowCytometry.

Address correspondence to: Martin Prlic, Fred Hutchinson Cancer Center, E5-110, 1,100 Fairview Ave. N, Seattle, Washington 98,109, USA. Phone: 206.667.2216; Email: mprlic@fredhutch.org. Or to: Alpana Waghmare, Fred Hutchinson Cancer Center, E4-100, 1,100 Fairview Ave. N, Seattle, Washington 98,109, USA. Phone: 206.667.7329; Email: awaghmar@fredhutch.org.

Find articles by Konecny, A. in: | Google Scholar

1Vaccine And infectious disease division, fred hutchinson cancer center, seattle, washington, USA.

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