Lowered ratio of corticospinal excitation to inhibition predicts greater disability, poorer motor and cognitive function in multiple sclerosis.

Objective: Investigate excitatory-inhibitory (E/I) (im)balance using transcranial magnetic stimulation (TMS) in individuals with Multiple Sclerosis (MS) and determine its validity as a neurophysiological biomarker of disability. Methods: Participants with MS (n = 83) underwent TMS, cognitive, and motor function assessments. TMS-induced motor evoked potential amplitudes (excitability) and cortical silent periods (inhibition) were assessed bilaterally through recruitment curves. The E/I ratio was calculated as the ratio of excitation to inhibition. Results: Participants with greater disability (Expanded Disability Status Scale, EDSS≥3) exhibited lower excitability and increased inhibition compared to those with lower disability (EDSS<3). This resulted in lower E/I ratios in the higher disability group. Individuals with higher disability presented with asymmetrical E/I ratios between brain hemispheres, a pattern not present in the group with lower disability. In regression analyses controlling for demographics, lowered TMS-probed E/I ratio predicted variance in disability (R2 = 0.37, p < 0.001), upper extremity function (R2 = 0.35, p < 0.001), walking speed (R2 = 0.22, p = 0.005), and cognitive performance (R2 = 0.25, p = 0.007). Receiver Operating Characteristic curve analysis confirmed 'excellent' discriminative ability of the E/I ratio in distinguishing high and low disability. Finally, excitation superiorly correlated with the E/I ratio than overall inhibition in both hemispheres (p ≤ 0.01). Conclusion: The E/I ratio is a potential neurophysiological biomarker of disability level in MS, especially when assessed in the hemisphere corresponding to the weaker body side. Interventions aimed at increasing cortical excitation or reducing inhibition may restore E/I balance potentially stalling progression or improving function in MS.

Amplification and Attenuation of Asymmetry via Kinetically Controlled Seed-Induced Supramolecular Polymerization.

The amplification of asymmetry in supramolecular polymers has recently garnered significant attention. While asymmetry amplification has predominantly been explored under thermodynamic conditions, the kinetic aspect of this process unveils intriguing observations, yet is scarcely reported in the literature. Herein, drawing inspiration from macromolecular systems, we propose a novel strategy for enhancing asymmetry in supramolecular polymers through a seed-induced supramolecular polymerization approach under kinetic conditions, employing a naphthalene diimide-derived monomer (ANSG) for template-induced supramolecular polymerization, utilizing adenosine triphosphate (ATP) and pyrophosphate (PPi) as templates. A chiral seed comprising [ANSG-ATP]S effectively amplifies the overall supramolecular asymmetry when exposed to a mixture of achiral templates (PPi) and monomers (ANSG), owing to its efficient seeding characteristics under kinetic conditions. As a result of efficient co-operativity, conversely, employing an achiral seed [ANSG-PPi]S in a mixture of chiral templates (ATP) and monomers (ANSG) results in the attenuation of asymmetry, highlighting the effective modulation achievable through the seeding approach, -an unprecedented observation in the field. Exploiting the efficient aggregation-induced emission enhancement (AIEE) of the resultant supramolecular polymers further extends the amplification and attenuation of circularly polarized luminescence (CPL) as a potential function.

Sleep apnea evokes right hemisphere dominance and psychological disorders: An exploratory study.

BACKGROUND: Obstructive sleep apnea (OSA) is considered one of the major causes of sleep disorders and psychological disorders in individuals. Brain asymmetry (BA) demonstrates individual hemispheric activity and psychological disorders. This study aimed to explore the characteristics of BA and psychology in OSA. METHODS: Enrolment of patients for sleep assessment at the Sleep Medicine Center. Clinical characteristics, handedness, and psychological scales were prospectively collected from subjects. Subsequently, EEG power in alpha, beta, and theta bilaterally was calculated for the rest and sleep phases. RESULTS: A total of 152 OSA and 21 non-OSA subjects were included in the study. In the frontal, central and occipital regions, OSA exhibited increased interhemispheric asymmetry with increasing apnea-hypopnea index (AHI) during rest and sleep. Simultaneously, the results showed that greater activity in the right hemisphere was positively associated with anxiety and extraversion, while inversely with positive and lie scale. In addition, the results show that OSA contributes to abnormal BA fluctuations during sleep. CONCLUSIONS: Our results suggest that sleep disorders associated with apnea-hypopnea and arousal may contribute to increased BA during sleep. Such changes may persist into wakefulness with psychological traits.

What does lack of language lateralization signify? Evidence of fluctuating asymmetry rather than hemispheric equipoise on non-lateralized tasks.

In a study of patterns of language laterality in left- and right-handers, Woodhead et al. (Woodhead ZVJ, Thompson PA, Karlsson EM, Bishop DVM. 2021 R. Soc. Open Sci. 8, 200696. (doi:10.1098/rsos.200696)) noted that several tasks showed no bias to the left hemisphere in left-handed individuals. This might appear to suggest that these functions were mediated by the two hemispheres working together equally-what can be termed 'hemispheric equipoise'. Here, I consider an alternative possibility that individuals show lateral bias on these tasks, but the bias can occur to either the left or right-a form of fluctuating asymmetry. Further analysis of the distributions of data from individuals in Woodhead et al. is compared with simulated data. The pattern of results suggests that the impression of hemispheric equipoise may be an artefact of reliance on group data: even though the group mean does not differ from zero, a high proportion of individuals are biased to the left or right.

Insights into left-right asymmetric development of chicken ovary at the single-cell level.

Avian ovaries develop asymmetrically apart from prey birds, with only the left ovary growing more towards functional organs. Here, we analyze over 135,000 cells from chick's left and right ovaries at six distinct embryonic developmental stages utilizing single-cell transcriptome sequencing. We delineate gene expression patterns across 15 cell types within these embryo ovaries, revealing side-specific development. The left ovaries exhibit cortex cells, zygotene germ cells, and transcriptional changes unique to the left side. Differential gene expression analysis further identifies specific markers and pathways active in these cell types, highlighting the asymmetry in ovarian development. A fine-scale analysis of the germ cell meiotic transcriptome reveals seven distinct clusters with gene expression patterns specific to various meiotic stages. The study also identifies signaling pathways and intercellular communications, particularly between pre-granulosa and germ cells. Spatial transcriptome analysis shows the asymmetry, demonstrating cortex cells exclusively in the left ovary, modulating neighboring cell types through putative secreted signaling molecules. Overall, this single-cell analysis provides insights into the molecular mechanisms of the asymmetric development of avian ovaries, particularly the significant role of cortex cells in the left ovary.

Botulinum toxin treatment for hemifacial spasm: harmonising neurological and aesthetic outcomes.

Hemifacial spasm (HFS) represents a challenging cranial movement disorder primarily affecting the facial nerve innervated muscles, with significant prevalence among Asians. Botulinum toxin type A (BoNT/A) injections, established as a primary therapeutic intervention since FDA approval, offer considerable effectiveness in alleviating spasms, albeit accompanied by challenges such as temporary effects and potential adverse events including facial asymmetry. This comprehensive review underscores the crucial need for harmonising neurological benefits and aesthetic outcomes in HFS management. The discussion delves into the interplay between facial aesthetics and neurological objectives in BoNT/A injections, emphasising precise techniques, dosages, and site considerations. Distinct aspects in neurological and aesthetic domains are also examined, including detailing the targeted muscles and injection methodologies for optimal therapeutic and aesthetic results. Importantly, evidence regarding various BoNT/A formulations, recommendations, and reconstitution guidelines in both neurology and aesthetics contexts are provided, along with a schematic approach outlining the stepwise process for BoNT/A injection in HFS treatment, addressing critical areas such as orbicularis oculi muscle sites, eyebrow correction strategies, mid- and lower-face considerations, contralateral injection sites, and post-injection follow-up and complication management. By highlighting the culmination of neurological efficacy and facial esthetics in BoNT/A treatment for HFS patients, this review proposes a holistic paradigm to achieve balanced symptomatic relief and natural aesthetic expression, ultimately enhancing quality of life for individuals grappling with HFS.

EXPRESS: Hemispheric Asymmetry for Global-Local Processing: Effects of Stimulus Category and Ageing.

Hemispheric asymmetry has been reported for global-local processing in young and older adults, with global processing specialised in the right hemisphere (RH-global specialisation) and local processing specialised in the left hemisphere (LH-local specialisation). Questions persist regarding the extent to which hemispheric asymmetry is influenced by stimulus category (verbal stimuli processed in the left hemisphere; visuospatial stimuli processed in the right hemisphere). Some evidence suggests stimulus category does not influence hemispheric asymmetry (stimulus-independent account) while other evidence suggests it does (stimulus-dependent account). In older adults, there was evidence of a local-processing advantage, believed to result from slower and less accurate performance in right-hemisphere compared to left-hemisphere functioning-the right-hemisphere ageing hypothesis. We examined hemispheric asymmetry for global-local processing in young and older participants with three hierarchical figures (letters, verbalisable objects, nonverbalisable shapes), in a within-subjects design using a divided-attention paradigm and unilateral presentation. Our findings for letters and verbalisable objects support the stimulus-independent account-young and older participants demonstrated RH-global specialisation and LH-local specialisation regardless of stimulus category. In older participants, we also found a local-processing advantage for all three stimulus categories-an advantage best explained as faster and more accurate performance in local processing regardless of the visual field of stimulus presentation. Overall, we found hemispheric asymmetry for global-local processing in both young and older adults, and differences in global processing between young and older adults. Future investigation is suggested for the hemispheric asymmetry found in global-local processing of nonverbalisable shapes, and the mechanisms underlying age-related changes in global processing.

Brain of miyoshi myopathy/dysferlinopathy patients presents with structural and metabolic anomalies.

Miyoshi myopathy/dysferlinopathy (MMD) is a rare muscle disease caused by DYSF gene mutations. Apart from skeletal muscles, DYSF is also expressed in the brain. However, the impact of MMD-causing DYSF variants on brain structure and function remains unexplored. To investigate this, we utilized magnetic resonance (MR) modalities (MR volumetry and 31P MR spectroscopy) in a family with seven children, four of whom have the illness. The MMD siblings showed distinct differences from healthy controls: (1) a significant (p < 0.001) right-sided volume asymmetry (+ 232 mm3) of the inferior lateral ventricles; and (2) a significant (p < 0.001) decrease in [Mg2+], along with a modified energy metabolism profile and altered membrane turnover in the hippocampus and motor and premotor cortices. The patients' [Mg2+], energy metabolism, and membrane turnover measures returned to those of healthy relatives after a month of 400 mg/day magnesium supplementation. This work is the first to describe anatomical and functional abnormalities characteristic of neurodegeneration in the MMD brain. Therefore, we call for further examination of brain functions in larger cohorts of MMD patients and testing of magnesium supplementation, which has proven to be an effective corrective approach in our study.

The impact of fine motor activities like playing musical instruments on the thickness and strength of the flexor digitorum muscle.

BACKGROUND: This study aimed to explore the impact of occupational activities involving extensive finger movement on the muscular characteristics of the forearms. In particular, the flexor digitorum (FD) muscular thickness and strength asymmetry between right and left hand were compared between musicians and non-musicians. METHODS: Ultrasonography was employed to measure the thickness of the FD in each hand, while a validated custom-made device was used to assess the strength of the flexor and extensor digitorum (ED). Initially, muscle differences were estimated by computing the asymmetry index between dominant and non-dominant hands. To assess potential occupational disparities, comparisons of the asymmetry index were conducted between 25 right-handed instrumental musicians and 25 right-handed non-musicians. RESULTS: Musicians exhibited lower asymmetry between dominant and non-dominant hands in both FD thickness and ED strength when compared to non-musicians. This effect was particularly pronounced in musicians playing instruments that extensively use the left-hand fingers (e.g., violinists). CONCLUSIONS: Occupational activities, such as playing a musical instrument, can alter forearm muscle mass and strength distribution between dominant and non-dominant hands. This underscores the importance of considering occupational parameters in clinical or experimental interventions and musculoskeletal assessments.

Beyond Single-Cycle Autonomous Molecular Machines: Light-Powered Shuttling in a Multi-Cycle Reaction Network.

Biomolecular machines autonomously convert energy into functions, driving systems away from thermodynamic equilibrium. This energy conversion is achieved by leveraging complex, kinetically asymmetric chemical reaction networks that are challenging to characterize precisely. In contrast, all known synthetic molecular systems in which kinetic asymmetry has been quantified are well described by simple single-cycle networks. Here, we report on a unique light-driven [2]rotaxane that enables the autonomous operation of a synthetic molecular machine with a multi-cycle chemical reaction network. Unlike all prior systems, the present one exploits a photoactive macrocycle, which features a different photoreactivity depending on the binding sites at which it resides. Furthermore, E to Z isomerization reverses the relative affinity of the macrocycle for two binding sites on the axle, resulting in a multi-cycle network. Building on the most recent theoretical advancements, this work quantifies kinetic asymmetry in a multi-cycle network for the first time. Our findings represent the simplest rotaxane capable of autonomous shuttling developed so far and offer a general strategy to generate and quantify kinetic asymmetry beyond single-cycle systems.

Correcting facial asymmetry through guided plate assisted mandibular angle osteotomy.

Background: Asian women prefer a smooth and narrowed mandibular appearance. The purpose of the retrospective cohort study is to evaluate guide plate-assisted mandibular angle ostectomy (MAO) in improving mandibular symmetry for Asian female patients with mandibular angle hypertrophy (MAH) with normal occlusal relationship. Methods: We retrospectively examined 11 patients with asymmetry MAH with normal occlusal relationship who received MAO at Shanghai Ninth People's Hospital between September, 2020, and January, 2022. Preoperative plans were designed based on CT data and executed using metal guide plate during the operation. Preoperative and one-week postoperative CT scans were used to assess measurements including Height_Go, Divergence_Go, ∠ZyZy-GoGo, and osteotomy volume, to evaluate symmetry. For precision, compare the postoperative CT with the preoperative design, assessing osteotomy distance, angle, and volume error. Patient satisfacation was evaluated with Likert Scale in 6-month follow-up. Secondary lipofilling procedures were given as appropriate. Statistical analysis was performed using paired t-tests in SPSS. Results: The mean age of the 11 patients was 28.5 years (range 23-34 years). 2 of these underwent lipofilling procedures. No complications were observed during the following-up. Postoperative results were not statistically different from the design, demonstrating a precision of within 2 mm. Height_Go disparity within 5 mm get corrected notably, reducing asymmetry from 15.09% preoperatively to 2.74% postoperatively. Patients satisfaction was rated at 4.5 out of 5 in 6 month follow-up. Conclusions: Guide plate-assisted mandibular angle osteotomies achieve effective and precise surgery. This approach demonstrates a safe option for correction for mandibular asymmetry, achieving patient satisfaction.

Angle-Specific Analysis of Isokinetic Quadriceps and Hamstring Strength at 6 and 12 Months After Unilateral ACL Reconstruction.

BACKGROUND: Quadriceps and hamstring strength deficits are related to the increased risk of reinjury after anterior cruciate ligament reconstruction (ACLR). HYPOTHESIS: Knee angle-specific quadriceps and hamstring strength differences would be observed in patients with ACLR 6 and 12 months after surgery. STUDY DESIGN: Case-series. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 23 postprimary unilateral ACLR patients followed-up at 6 and 12 months postoperatively and 25 controls were included. Isokinetic knee extension and flexion strength were evaluated at 60 deg/s from 20° to 90°. Statistical parametric mapping were performed to explore the angle-specific strength and the limb symmetry index (LSI). RESULTS: At 6 months postoperatively, the reconstructed leg demonstrated lower knee extension and flexion strength than the contralateral (20°-77°, 24°-90°) (P < 0.01) and control legs (22°-90°, 40°-82°) (P < 0.01). From 6 months to 12 months, knee extension (60°-90°) and flexion (20°-79°) strength improved in the reconstructed leg (P < 0.05), while LSI remained unchanged (P > 0.02). At 12 months, knee extension strength differences persisted in the reconstructed leg compared with the contralateral (20°-81°) and controls (25°-63°) (P < 0.01). ACLR patients had lower LSI of knee extension strength at 6 (20°-59°) and 12 (24°-57°) months postoperatively than the controls (P < 0.02). CONCLUSION: The reconstructed leg exhibited differences in knee extension strength compared with the contralateral and control legs. Although bilateral knee extension strength increased from 6 to 12 months postoperatively, LSI did not show improvement during this period. CLINICAL RELEVANCE: Quadriceps restoration was observed only in knee flexion angles greater than 60° compared with controls. Future studies should investigate whether knee extension strength, especially in lower flexion angles, can be enhanced through rehabilitation programs. Furthermore, assessing the impact of this improvement on long-term outcomes and reinjury risk in ACLR patients is warranted.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: Exploratory Outcomes and Open-Label Extension.

BACKGROUND: A randomized trial suggested that reducing left-sided subthalamic stimulation amplitude could improve axial dysfunction. OBJECTIVES: To explore open-label tolerability and associations between trial outcomes and asymmetry data. METHODS: We collected adverse events in trial participants treated with open-label lateralized settings for ≥3 months. We explored associations between trial outcomes, location of stimulation and motor asymmetry. RESULTS: 14/17 participants tolerated unilateral amplitude reduction (left-sided = 10, right-sided = 4). Two hundred eighty-four left-sided and 1113 right-sided stimulated voxels were associated with faster gait velocity, 81 left-sided and 22 right-sided stimulated voxels were associated with slower gait velocity. Amplitude reduction contralateral to shorter step length was associated with 2.4-point reduction in axial MDS-UPDRS. Reduction contralateral to longer step length was associated with 10-point increase in MDS-UPDRS. CONCLUSIONS: Left-sided amplitude reduction is potentially more tolerable than right-sided amplitude reduction. Right-sided more than left-sided stimulation could be associated with faster gait velocity. Shortened step length might reflect contralateral overstimulation.

Automated Estimation of Thoracic Rotation in Chest X-ray Radiographs: A Deep Learning Approach for Enhanced Technical Assessment.

OBJECTIVES: This study aims to develop an automated approach for estimating the vertical rotation of the thorax, which can be used to assess the technical adequacy of chest X-ray radiographs (CXRs). METHODS: Total 800 chest radiographs were used to train and establish segmentation networks for outlining the lungs and spine regions in chest X-ray images. By measuring the widths of the left and right lungs between the central line of segmented spine and the lateral sides of the segmented lungs, the quantification of thoracic vertical rotation was achieved. Additionally, a life-size, full body anthropomorphic phantom was employed to collect chest radiographic images under various specified rotation angles for assessing the accuracy of the proposed approach. RESULTS: The deep learning networks effectively segmented the anatomical structures of the lungs and spine. The proposed approach demonstrated a mean estimation error of less than 2° for thoracic rotation, surpassing existing techniques and indicating its superiority. CONCLUSIONS: The proposed approach offers a robust assessment of thoracic rotation and presents new possibilities for automated image quality control in chest X-ray examinations. ADVANCES IN KNOWLEDGE: This study presents a novel deep learning-based approach for the automated estimation of vertical thoracic rotation in chest X-ray radiographs. The proposed method enables a quantitative assessment of the technical adequacy of CXR examinations and opens up new possibilities for automated screening and quality control of radiographs.

Analysis of functional network asymmetry in major depressive disorder under four fNIRS tasks.

BACKGROUND: Research in functional asymmetry of Major Depressive Disorder (MDD) under different tasks is crucial for clinical diagnose. METHODS: Fifty individuals with MDD and twenty healthy controls (HCS) were recruited for hemodynamic data collection under four fNIRS tasks (Emotional picture, Verbal fluency, Fingering and Negative emotional picture description task). Integral values and functional connectivity strength were employed to probe neural activation and functional connectivity in frontal and temporal lobes in MDD. Following, asymmetry characteristic of the frontal cortex between MDD and HCS under four tasks were carefully analyzed and compared. RESULTS: Individuals with MDD demonstrated heightened connectivity between the frontal and right temporal lobes and reduced connectivity between the frontal and left temporal lobes compared to HCS in all tasks. Additionally, MDD exhibited attenuated activation in the left frontal lobes and exaggerated activation in the right frontal lobes, diverging from HCS. Furthermore, the disparities in left-right asymmetry characteristic of frontal cortex activation between MDD and HCS were more pronounced during the combined task. LIMITATIONS: Further research is required to grasp the neurophysiological mechanisms governing left-right asymmetry across various tasks and the influence of task-induced brain fatigue on cerebral cortex hemodynamics in MDD. CONCLUSION: The left-right asymmetry feature provides valuable neurophysiological insights for diagnosing MDD clinically. Variations in activation patterns and functional connectivity features between MDD and HCS are closely tied to the task chosen. Thus, in clinical practice, carefully selecting appropriate fNIRS tasks and relevant features can significantly improve the diagnostic accuracy of MDD.

Frontal alpha asymmetry predicts subsequent social decision-making: A dynamic multilevel, neural, and developmental perspective.

Social motivation, the human desire to engage with others, is likely to underlie higher levels of social cognition and the formation of interpersonal relationships. Yet, this topic has been understudied in adolescents despite the critical developmental and maturational changes that occur during this period and the relevance of social motivation to clinical and neurodevelopmental disorders. Using electroencephalography (EEG) and an implicit-association paradigm (Choose-A-Movie Task; Dubey et al., 2015), we examined how brain responses underlying socially motivated decisions informed future decisions in 54 youth (aged 10-14 years) and 50 young adults (aged 18-33 years). As the first study to use this task during EEG recording, we implemented time-frequency analyses and a trial-by-trial dynamic statistical approach. Results suggested that both age groups preferred low-effort choices and increasingly preferred nonsocial choices over time. P3 amplitude also increased over time and was sensitive to effortful decisions, particularly for adults, but not social content. Both groups showed larger leftward frontal alpha asymmetry (FAA) during nonsocial feedback, and FAA predicted future decisions differently for adults than youth. The current study highlights FAA and trial-by-trial analyses as useful tools in understanding the neural mechanisms underlying socially motivated decisions, which differ across development, time, and individuals.

The First-Night Effect of sleep occurs over non-consecutive nights in unfamiliar and familiar environments.

The first night in an unfamiliar environment is marked by reduced sleep quality and changes in sleep architecture. This so-called First-Night Effect (FNE) is well established for two consecutive nights and lays the foundation for including an adaptation night in sleep research to counteract FNEs. However, adaptation nights rarely happen immediately before experimental nights, which raises the question of how sleep adapts over non-consecutive nights. Furthermore, it is yet unclear, how environmental familiarity and hemispheric asymmetry of slow-wave sleep (SWS) contribute to the explanation of FNEs. To address this gap, 45 healthy participants spent two weekly separated nights in the sleep laboratory. In a separate study, we investigated the influence of environmental familiarity on 30 participants who spent two non-consecutive nights in the sleep laboratory and two nights at home. Sleep was recorded by polysomnography. Results of both studies show that FNEs also occur in non-consecutive nights, particularly affecting wake after sleep onset, sleep onset latency, and total sleep time. Sleep disturbances in the first night happen in both familiar and unfamiliar environments. The degree of asymmetric SWS was not correlated with the FNE but rather tended to vary over the course of several nights. Our findings suggest that non-consecutive adaptation nights are effective in controlling for FNEs, justifying the current practice in basic sleep research. Further research should focus on trait- and fluctuating state-like components explaining interhemispheric asymmetries.

Cytosolic protein translation regulates cell asymmetry and function in early TCR activation of human CD8+ T lymphocytes.

Introduction: CD8+ cytotoxic T lymphocytes (CTLs) are highly effective in defending against viral infections and tumours. They are activated through the recognition of peptide-MHC-I complex by the T-cell receptor (TCR) and co-stimulation. This cognate interaction promotes the organisation of intimate cell-cell connections that involve cytoskeleton rearrangement to enable effector function and clearance of the target cell. This is key for the asymmetric transport and mobilisation of lytic granules to the cell-cell contact, promoting directed secretion of lytic mediators such as granzymes and perforin. Mitochondria play a role in regulating CTL function by controlling processes such as calcium flux, providing the necessary energy through oxidative phosphorylation, and its own protein translation on 70S ribosomes. However, the effect of acute inhibition of cytosolic translation in the rapid response after TCR has not been studied in mature CTLs. Methods: Here, we investigated the importance of cytosolic protein synthesis in human CTLs after early TCR activation and CD28 co-stimulation for the dynamic reorganisation of the cytoskeleton, mitochondria, and lytic granules through short-term chemical inhibition of 80S ribosomes by cycloheximide and 80S and 70S by puromycin. Results: We observed that eukaryotic ribosome function is required to allow proper asymmetric reorganisation of the tubulin cytoskeleton and mitochondria and mTOR pathway activation early upon TCR activation in human primary CTLs. Discussion: Cytosolic protein translation is required to increase glucose metabolism and degranulation capacity upon TCR activation and thus to regulate the full effector function of human CTLs.

Conscience, Disobedience, and Standard of Care.

In the article "Principled Conscientious Provision: Referral Symmetry and Its Implications for Protecting Secular Conscience," Abram L. Brummett, Tanner Hafen, and Mark C. Navin reject what they call the "referral asymmetry" in U.S. conscientious objection law in medicine, which recognizes rights of conscientiously objecting physicians to withhold referrals for medical interventions but does not (yet) recognize rights of physicians to make referrals for medical interventions to which they are morally committed but to which their health care institutions are morally opposed. This commentary concentrates on a second asymmetry, namely, the relationship of a health care provider's referral or nonreferral to the medical standard of care. The commentary argues that this second asymmetry seems to require action more appropriately recognized as civil disobedience than conscientious provision of referral.

Local Dipole Modulation Toward High Fill Factor in Organic Solar Cells.

Dipole moment arrangement in organic semiconductors plays a critical role in affecting the intermolecular packing, determining optoelectronic properties and device performance. Here, to get the desired fill factor (FF) values in organic solar cells (OSCs), the local dipole of non-fullerene acceptors (NFAs) is modulated by changing the molecular asymmetries. Two NFAs, AA-1 and AA-2 are designed and synthesized, which have different substitutions of alkyl and alkoxyl groups. The unidirectional asymmetry in AA-2 creates distinct local dipoles, while the bidirectional asymmetry in AA-1 mitigates dipole variation. Despite the minimal impact on monomolecular properties, the local dipole moment significantly influences terminal group packing modes in the film state. This, in turn, enhances the relative dielectric constant, prolongs exciton lifetime, and reduces sub-bandgap defect states. Consequently, PBDB-TF:AA-2-based OSCs achieve an exceptional FF of 0.830 and a power conversion efficiency (PCE) of 18.3%, with a ternary device reaching a PCE of 19.3%. This work highlights the potential of dipole modulation in material design to get ideal FF values for high-performance OSCs.