Tag: Academic research

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STAT+: Hope for Kendall Square’s lab market

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Good morning. In today’s news, we have: pricing conundrums, lab demand, and drug shortages.

The need-to-know this morning

  • Sanofi said it was halting a Phase 3 study of its drug riliprubart in a rare autoimmune disease after an interim analysis showed the therapy was not effective. It’s the latest blow to the French firm’s R&D efforts, which new CEO Belén Garijo has been brought in to revitalize.
  • Parabilis Medicines, a developer of cancer medicines, raised $670 million in an initial public offering. It’s the largest-ever biotech IPO, topping obesity drugmaker Kailera Therapeutics’ $625 million debut in April. 

European countries at odds over drug-pricing policies

In Europe, countries are grappling with what to do about drug prices as they contend with conflicting pressures. Aging populations and growing rates of chronic disease are straining their budgets, but, at the same, the U.S. and drugmakers are demanding they pay more for medicines.

Continue to STAT+ to read the full story…

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mRNA Tails Play Key Role in Folding Regulatory Proteins

mRNA 3′ UTRs have hundreds of highly conserved nucleotides, but their biological roles are unclear. In a new study published in Cell titled, “mRNA 3′ UTRs chaperone intrinsically disordered regions to control protein activity,” researchers from Memorial Sloan Kettering (MSK) Cancer Center now demonstrates that mRNA 3′ UTRs play a key role assisting the folding of regulatory proteins. 

“The traditional view is that only specialized proteins act as ’chaperones’ to help other proteins fold correctly,” said Christine Mayr, MD, PhD, a member of the Sloan Kettering Institute and corresponding author on the paper. “Our research shows that RNA can do this, too—and that mRNAs act as their own chaperones for a group of important, hard-to-fold proteins.” 

While 3′ UTRs have traditionally been dismissed as key regulators, Mayr emphasizes that thousands of human 3′ UTRs have highly conserved sequences across vertebrates, offering a clue of their function. “Biology doesn’t usually preserve things that aren’t needed,” she says. 

Many larger, complex regulatory proteins, such as the transcription factors MYC, UTX, and JMJD3, possess long, flexible regions, named intrinsically disordered regions (IDRs), that do not fold into stable structures on their own.

The study showed that cells solve this folding problem using specialized compartments, known as mesh-like condensates. The 3′ UTR promotes IDR–IDR interactions and suppresses folding between domains. Results suggest that this chaperone activity prevents interference between hydrophobic clusters in the IDR with folding of the structured domain. 

The team identified more than 2,700 genes with highly conserved 3′ UTRs, or about one in every eight protein-coding genes in the human genome. The proteins expressed by these genes contain intrinsically disordered regions that require RNA chaperones to facilitate folding. 

“What we show is that for thousands of regulatory proteins in human cells, the genetic code alone isn’t enough to make a functional protein—you need the RNA chaperone too,” said Mayr. 

The study has practical implications for laboratory research. For thousands of regulatory proteins, removing the 3′ UTR allows researchers to study the misfolded, and less active version of the protein. 

The post mRNA Tails Play Key Role in Folding Regulatory Proteins appeared first on GEN – Genetic Engineering and Biotechnology News.

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Deep and repetitive transcranial magnetic stimulation improves motor dysfunction after basal ganglia infarction: preliminary findings on efficacy and electrophysiological mechanisms

ObjectiveTo observe the therapeutic effects of deep transcranial magnetic stimulation (dTMS) and repetitive transcranial magnetic stimulation (rTMS) on upper and lower limb motor dysfunction in patients with basal ganglia infarction, and to preliminarily explore their underlying electrophysiological mechanisms.MethodsThirty patients with motor dysfunction secondary to basal ganglia infarction, hospitalized at the Affiliated Hospital of North Sichuan Medical College between October 2024 and December 2025, were enrolled in this study. All eligible participants were randomly assigned to one of three treatment groups: dTMS (n = 10), rTMS (n = 10), or sham stimulation (n = 10). All patients in the three groups received routine medical treatment and conventional rehabilitation training. On this basis, the dTMS group was treated with 10 Hz dTMS, the rTMS group with 10 Hz rTMS, and the sham stimulation group with sham stimulation, 5 sessions per week for 2 consecutive weeks. Before treatment, on the first day after treatment, and at 30 days after treatment, the Fugl-Meyer Assessment (FMA), Berg Balance Scale (BBS), and Modified Barthel Index (MBI) were used to evaluate motor function of the affected side and activities of daily living. The resting motor threshold (rMT) and central motor conduction time (CMCT) of the affected hemisphere were measured simultaneously.ResultsThe baseline data among the three groups were comparable (all p > 0.05); After treatment, there was a statistically significant interaction between group and time in FMA-UE, FMA-LE, MBI, and BBS scores among the three groups (all p < 0.05); Compared with baseline, FMA-UE, FMA-LE, MBI, and BBS scores were significantly increased on the first day and at 30 days after treatment in all three groups (all p < 0.001); Compared with the sham stimulation group, the dTMS group exhibited higher FMA-UE, FMA-LE, MBI, and BBS scores on the first day and at 30 days after treatment (all p < 0.05); Compared with the rTMS group, the dTMS group showed no significant differences in FMA-UE and MBI scores on the first day after treatment (all p > 0.05), but higher FMA-LE and BBS scores (all p < 0.05), at 30 days after treatment, FMA-UE, FMA-LE, MBI, and BBS scores were all higher in the dTMS group (all p < 0.05). There was a statistically significant interaction between group and time in rMT and upper limb CMCT among the three groups after treatment (all p < 0.05); Compared with baseline, rMT and upper limb CMCT were significantly decreased on the first day and at 30 days after treatment in all three groups (all p < 0.001); Compared with the sham stimulation group, the dTMS group had lower rMT and upper limb CMCT on the first day and at 30 days after treatment (all p < 0.05); Compared with the rTMS group, the dTMS group showed lower rMT and upper limb CMCT on the first day after treatment (p < 0.05), at 30 days after treatment, rMT was lower (p < 0.05), while no significant difference was found in upper limb CMCT (p > 0.05).Conclusion(1) Both high-frequency dTMS and rTMS can improve upper limb motor dysfunction after basal ganglia cerebral infarction to some extent, and the therapeutic effect of dTMS lasts longer; (2) dTMS has a certain rehabilitative effect on lower limb motor and balance function; (3) The mechanisms underlying the improvement of motor dysfunction after basal ganglia cerebral infarction by high-frequency dTMS and rTMS may be associated with increased excitability of the affected cerebral cortex, enhanced function of the corticospinal tract pathway. In addition, dTMS can directly act on deeper and wider brain regions; (4) Both high-frequency dTMS and rTMS are safe.
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Predicting early neurological deterioration in acute branch atheromatous disease without reperfusion therapy: a machine learning model

BackgroundAcute branch atheromatous disease (BAD) is one of the leading contributors to morbidity and disability in Asia, and early neurological deterioration (END) is common in affected patients. This study aimed to establish machine learning models to predict the risk of END in patients without reperfusion therapy.MethodsPatients with acute BAD who did not receive reperfusion therapy were retrospectively enrolled. Core predictive features were selected by LASSO regression with bootstrap stability assessment, and we used seven machine learning algorithms to build models. XGBoost was selected based on validation performance, nested cross-validation, and 1,000-iteration bootstrap validation. A spline logistic regression model served as the non-linear baseline. SHAP analysis was used to explain the model and develop a simple scoring system. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC), and clinical utility was evaluated using decision curve analysis (DCA).ResultsA total of 369 patients were included in our research. We screened predictive factors with LASSO regression and ultimately identified five key variables. These included maximum infarct area, lactate dehydrogenase (LDH), number of infarct slices, admission systolic blood pressure (SBP), and neutrophil count. The XGBoost model achieved the best overall performance, with AUC of 0.927 in the training set and 0.846 in the validation set. Nested cross-validation yielded an unbiased AUC of 0.866 (95% CI: 0.817–0.925), and bootstrap validation produced a mean OOB AUC of 0.855 (95% CI: 0.760–0.941). The scoring system stratified patients into low (0–6 points), intermediate (7–13 points), and high (14–20 points) risk groups. DCA demonstrated favorable clinical utility. SHAP analysis also indicated that maximum infarct area and LDH were the top two predictors of END.ConclusionAn XGBoost-based prediction model and a simple scoring system, integrating maximum infarct area, LDH, number of infarct slices, admission SBP, and neutrophil count, provide reliable END risk prediction for acute BAD patients without reperfusion therapy.
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Longitudinal changes in MMN and P3 during emotional processing in adolescents who engage in NSSI: a 12-week follow-up study

BackgroundAdolescents with nonsuicidal self-injury (NSSI) often show deficits in negative emotion regulation. Within the dual-process framework of implicit and explicit emotion regulation, these deficits may reflect an automatic bias toward negative information and insufficient later-stage controlled regulation. Whether routine clinical intervention modifies both early automatic detection and later controlled evaluation of negative emotional information remains unclear.MethodsIn a longitudinal sample of 32 adolescents with NSSI, we examined changes in mismatch negativity (MMN) and P3 components elicited during an emotional oddball task before and after a 12-week clinical intervention. At baseline and Week 12, participants completed clinical assessments and a two-choice visual emotional oddball task containing neutral standards and negative, positive, and neutral deviants while EEG was recorded. MMN (Fz, 240–300 ms) and P3 (Pz, 450–650 ms) amplitudes were derived from deviant-minus-standard difference waves, indexing pre-attentive deviance detection and controlled evaluation, respectively.ResultsThe intervention selectively modulated neurocognitive processing of negative deviants. Self-injury ideation days (p = .036) and NSSI episode frequency (p = .007) both significantly decreased. MMN absolute amplitude to negative stimuli decreased significantly (p = .047), suggesting attenuated automatic salience detection, whereas P3 amplitude to negative stimuli increased significantly (p = .027), indicating enhanced controlled evaluation. Responses to positive and neutral conditions and behavioural performance remained stable. No baseline ERP–clinical correlations emerged; post-intervention, NSSI ideation days correlated with positive P3 (r = 0.380, p = .032), and episode frequency with neutral P3 (r = 0.461, p = .008).ConclusionsA 12-week intervention may attenuate automatic negative bias while enhancing controlled evaluative processing in adolescents with NSSI, consistent with the implicit–explicit framework. MMN and P3 may serve as candidate biomarkers and temporally sensitive tools for tracking intervention response when behavioural performance is stable.
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The therapeutic role of self-transcendence in moral injury recovery: theory, mechanisms, and clinical implications

A growing body of psychological and neuroscientific research suggests that moral injury (MI) involves maladaptive self-referential processing, including disruptions in moral identity, rigid negative self-appraisals, and impaired meaning-making following exposure to potentially morally injurious events (PMIEs). Building on Mindfulness-to-Meaning Theory (MMT), this paper proposes self-transcendence (ST)—a metacognitive state characterized by reduced self-focus, expanded awareness, transcendent affect, and prosocial meaning—as a potential mechanism for MI recovery. Within MMT, mindfulness practice is theorized to cultivate ST via decentering and meta-awareness, processes that broaden attentional scope, promote flexible cognitive reappraisal, and modulate habitual self-referential processing. Mindfulness and contemplative research further link ST to increased cognitive flexibility, reduced in shame-focused narrative self-processing, and adaptive integration of emotionally and morally disruptive experiences. Drawing on an integrative review of ST-consistent and MI-related mechanisms, this paper argues that fostering ST through mindfulness-based and contemplative practices may reduce rigid self-focus, expand interpretive frameworks of meaning, and support moral identity repair and meaning-making. Implications are discussed for designing interventions that intentionally cultivate ST as both standalone approaches and modular components, while acknowledging current limitations in measurement, readiness assessment, and the reliable induction of ST states.
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Association between plasma proBDNF levels and cognitive impairment in patients with alcohol dependence: a case–control and longitudinal study

BackgroundAlcohol dependence is frequently accompanied by cognitive impairment. Brain-derived neurotrophic factor (BDNF) signaling plays a critical role in synaptic plasticity, while the precursor form, proBDNF, has been increasingly implicated in neurodegenerative and psychiatric disorders. However, the association between plasma proBDNF levels and cognitive impairment in alcohol dependence remains unclear.MethodsEighty male patients with alcohol dependence and forty-two matched healthy controls were enrolled. Plasma proBDNF levels were measured via enzyme-linked immunosorbent assay (ELISA). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Modified Wisconsin Card Sorting Test (M-WCST), and the Verbal Fluency Test (VFT). Forty-one patients were reassessed after four weeks of abstinence. Group comparisons and correlation analyses were performed.ResultsPatients with alcohol dependence exhibited significantly elevated plasma proBDNF levels and impaired cognitive performance compared with controls. Plasma proBDNF levels were positively correlated with alcohol consumption severity, and linked to global cognitive deficits alongside nuanced executive performance variations. After four weeks of abstinence, plasma proBDNF levels decreased and cognitive performance improved; however, changes in proBDNF were weakly associated with cognitive recovery.ConclusionsElevated plasma proBDNF levels are associated with alcohol dependence severity and cognitive impairment, suggesting that proBDNF may serve as a peripheral biomarker reflecting the dynamic neurocognitive status in alcohol dependence.