bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre‐Transplant Immunophenotyping in Pediatric Heart Transplant: A Role for the Immunologist?
Authors: Gunderman Lauren , Lancki Nicola , Madden Brian , Ahmed Aisha
Published: February 2025

Background

Pediatric heart transplant recipients are at risk for complications from prolonged exposure to immunosuppressive drugs, possibly worsened due to over‐immune suppression in patients with pre‐existing immune abnormalities.

Methods

This was a retrospective, single‐center pediatric cohort study and review of baseline immune evaluation in patients referred for heart transplant. Referrals included were from January 1, 2021, to June 31, 2022.

Results

Fifty‐one patients were referred during the time period with a median age of 5 years (ranging 1 month‐20 years). Twenty‐seven total patients were transplanted. Given a lack of standardized immune evaluation, results were focused on lymphocyte quantitation, functional testing when available, and T‐cell subsets. Outcome measures focused on the number of infections and episodes of rejection requiring treatment. In total, 44.4% of patients experienced rejection, and the mean number of infections in the first 12 months post‐heart transplant was 2.1 (range 0–7 total infections).

Conclusions

Baseline immune evaluation showed general T and B cell lymphopenia, without a clear connection between outcome differences for the number of infections or episodes of rejection requiring treatment. This small study demonstrated some differences in immune function in patients prior to heart transplant but was inadequately powered to draw conclusions about the effects of immunosuppression on post‐transplant outcomes.
Learning to avoid: The long‐term effects of adolescent welfare participation on voting habits in adulthood
Authors: Micatka Nathan K.
Published: February 2025

Welfare participation is associated with lower turnout among adults. For many citizens, however, their first experiences with welfare occur during a critical time of political development in adolescence. Does growing up on welfare lower turnout in young adulthood? I identify three mechanisms linking adolescent welfare experience to voting: stigma, the absence of pro‐civics role models, and ineffective support from government welfare programs. Using the National Longitudinal Survey of Youth 1997, I find that non‐Hispanic white adolescents who grow up on welfare are 6–17 percentage points less likely to vote compared to those without welfare experience. Adolescent welfare participation is unrelated to voting among Black and Hispanic youths. Interviews and focus groups find support for the three mechanisms. These findings highlight the importance of adolescent policy experiences for voting.
The Moderating Role of Workplace Autonomy on Corruption Control Strategies: Evidence From 33 South Korean Ministries
Authors: Kim Danee , Porumbescu Gregory A.
Published: February 2025

Corruption research highlights the importance of organizational and individual correlates, such as corruption control strategies or public employee attitudes. In this study, we integrate these research streams by examining whether the effectiveness of two common organizational approaches to controlling corruption—value‐oriented strategies, which emphasize ethical decision‐making, and compliance‐oriented strategies, which rely on monitoring, audits, and punishment—depends on perceptions of workplace autonomy. To explore this, we use novel administrative data on corruption, along with codes of ethics and survey data from 1235 career public servants across 33 South Korean ministries. Findings suggest greater perceived autonomy is associated with greater corruption tolerance in organizational contexts where compliance‐oriented corruption control strategies are prevalent. Conversely, greater perceived autonomy is associated with lesser corruption tolerance when value‐oriented corruption control strategies are prevalent. These findings contribute to administrative corruption research by illustrating how individual perceptions of their workplace shape the efficacy of organizational corruption control strategies.
The Socio‐Political Context of Citizen Activism: An International Comparative Perspective
Authors: Kaye‐Essien Charles Wharton
Published: February 2025

This paper examines the moderating effects of socio‐political factors on the influence of issue salience and prosocial values on citizen activism in different governance contexts. While the literature on citizen activism has examined the emergence, motivations, and channels of activism, we still lack a broader understanding of how different social (membership of social groups and sense of attachment to local communities) and political (ease of citizen involvement and trust in government) contexts affect people's ultimate decisions about activism in different governance systems. This paper fills this gap, drawing on a comparative research methodology and using data from the World Values Survey Wave 7.
Sharp Rate of the Accelerating Propagation for a Recursive System
Authors: Li Na , Pan Yingli , Su Ying
Published: February 2025

How to characterize the rate of accelerating propagation in recursive systems is a challenging topic though it has attracted great attention of theoretical and empirical ecologists. In this paper, we determine the sharp rate of accelerating propagation for a unimodal recursive system with a heavy‐tailed dispersal kernel through tracking of level sets of solutions with compactly supported initial data. It turns out that the solution level set satisfies for large , where is the level and is determined by the linearized system at zero.
Identification of Novel HLA‐B*58:01:51 Allele in Brazilian Individual
Authors: Fabreti‐Oliveira Raquel Aparecida , de Oliveira Cintia Keilla Fabreti , Nascimento Evaldo
Published: February 2025

Identification of the novel HLA‐B*58:01:51 allele in a Brazilian bone marrow donor.
Preparing to Operate: A Multinational Analysis of Practices and Perceptions of Surgical Residents
Authors: Lari Ali , Alherz Mohammad , Alshammasi Ahmed , Alzahrani Mohammad M. , Alraiyes Thamer , Almansouri Abdulrahman , Alnusif Naser
Published: February 2025

Introduction

Operative preparation among surgical residents is a critical aspect of surgical training, requiring a balance of technical and non‐technical skill development. Structured residency programmes have introduced both opportunities and challenges for residents, including navigating diverse educational resources and addressing barriers to effective preparation. This study aimed to examine operative preparation among surgical residents, focusing on their attitudes, motivations, barriers and strategies to assess the efficacy of residency programmes.

Methods

A cross‐sectional survey, designed by surgeons and surgical residents, gathered data from 201 surgical residents across various specialties and countries. The survey investigated demographics, practices, influences and experiences regarding residency programmes.

Results

The study revealed a positive correlation between time spent preparing and perceived preparedness, with residents spending more time preparing as they progressed in their residency. Barriers to preparation included limited time and energy as well as having a minimal role in the surgery. Motivations were centred around personal growth, as well as safety and complication avoidance. Common preparation techniques included reviewing imaging (88.6%), watching surgical videos (83.6%) and reviewing medical records (82.1%). Activities such as reviewing articles and mental rehearsal were utilised less but were strongly correlated with preparedness. Only 31% received formal training on preoperative preparation.

Conclusions

Surgical residency programmes need to address the diverse learning preferences of residents and provide a more structured approach to preparation. There is a need to optimise barriers and motivators to preoperative preparation and align expectations between tutors and residents to enhance the preparedness of surgical residents for the operating room.
Comparison of energy expenditure with level of amputation in patients with diabetes mellitus
Authors: Petric Jan Karel , Johnson Matthew J. , Jeans Kelly , Fortenberry Ariel R. G. , Wang Jijia , Tulchin‐Francis Kirsten , Wukich Dane K. , Graham Tiffany D. F.
Published: February 2025

Diabetes mellitus (DM) is the leading cause of non‐traumatic lower extremity amputations in the USA. After these amputations, patients exhibit reduced mobility and increased energy demands of walking. The best surgical practice is to preserve as much of a functional limb as possible, in part due to the fact that proximal amputations result in a greater increase in energy expenditure compared to more distal amputations. While differences in transfemoral, transtibial and partial foot amputation levels have been previously documented, no studies have directly compared transtibial and transmetatarsal amputees. The present study aimed to compare energy expenditure and patient‐reported outcomes in patients with diabetes mellitus who have undergone transmetatrsal (TMA) and transtibial amputations (TTA). Thirty‐nine DM participants with either unilateral TMA, unilateral TTA or no amputations (control group) participated in this observational study. Energy expenditure, heart rate (HR) and distance travelled during six‐minute walk test (6MWT), the Foot and Ankle Ability Measure (FAAM) and the Patient‐Reported Outcomes Measurement Information System (PROMIS‐29) were measured at a single research visit. No significant differences between the three groups were detected in energy expenditure, HR or distance covered during 6MWT, as well as in PROMIS‐29 or FAAM patient‐reported outcomes. While the results of this study suggest no differences in functional and patient‐reported outcomes between transmetatarsal and transtibial amputees, a larger sample size that would allow for control of comorbidities is needed.
The International Human Xenotransplantation Inventory: Current Data and Future Directions
Authors: Hu Xiaowei , Hawthorne Wayne J. , Buhler Leo
Published: February 2025

Background

The global demand for organ transplantation outpaces supply, necessitating innovative solutions. Xenotransplantation, using animal organs, cells, and tissues, is a promising solution to address the organ shortage. The World Health Organization and the International Xenotransplantation Association collaboratively established an online inventory in 2006 (www.humanxenotransplant.org) to catalog human xenotransplantation practices. The inventory, managed successively by the Geneva University Hospital and the Sichuan Provincial People's Hospital, aligns with the WHO directives for transparency and best practices in the field of transplantation.

Methods

Relevant data have been regularly collected from numerous sources (scientific publications, congresses, press articles, declarations of International Xenotransplantation Association members) by a dedicated team in Switzerland and China ensuring rigorous verification. The initial information is used to create a first entry in the database which is then completed when more details become available.

Results

As of May 2024, the inventory contained 54 entries of distinct xenotransplantation procedures undertaken on humans. From these data, various trends can be observed over the last two decades regarding the type of transplantation, their regulation status, and the source animal. Notably, recent high‐profile cases of solid organ transplantation involving kidneys and hearts were made feasible through years of progressive xenotransplantation research and ongoing changes to regulations.

Conclusions

Recent clinical applications of solid organ xenotransplantation suggests that more clinical procedures may soon follow for patients with end‐stage kidney or heart disease, or diabetes. Future perspectives advocate for increased funding and expansion of the current registry or its potential integration into a larger and more broadly internationally recognized registry, such as the Global Observatory on Donation and Transplantation (GODT).
Modified CD40L‐Activated B‐Cell Proliferation Model for Validating the Suppressive Activity of CD40‐CD154 Pathway Inhibitors
Authors: Zhang Man , Feng Hao , Huang Yahui , Hu Tianyi , Du Jiaxiang , Wang Yong , Chen Song , Pan Dengke , Zhu Lan , Chen Gang
Published: February 2025

Background

CD40‐CD154 pathway inhibitors are considered indispensable immunosuppressive drugs in xenotransplantation. At present, novel anti‐CD154 and anti‐CD40 monoclonal antibodies (mAbs) are continuously being developed. It is important to establish a simple and efficient in vitro method to evaluate the effectiveness of these therapeutic mAbs.

Methods

A modified CD40L‐activated B‐cell proliferation model was established using irradiated NIH/3T3 cells transfected with human CD40 ligand (hCD40L‐NIH/3T3) as stimulator cells and human or rhesus monkey peripheral blood mononuclear cells (PBMCs) as responder cells. After 8 days of culture, B‐cell proliferation was detected by flow cytometry. Various concentrations of anti‐CD40 or anti‐CD154 mAbs were added to the co‐culture system as an intervention. The inhibitory effects of anti‐CD154 and anti‐CD40 mAbs on the proliferation of B cells from humans and rhesus monkeys were studied and compared.

Results

After 8 days of co‐culture, the proliferation rate of B cells in both human and rhesus monkey PBMCs was more than 80%, and the expression of MHC‐II and the co‐stimulatory molecules CD80, CD86, and CD40 on B cells was significantly up‐regulated. All three anti‐CD154 mAbs showed a similar strong inhibitory effect on human B‐cell proliferation, but the inhibitory effect on the proliferation of rhesus monkey B cells was weaker than that on human B cells, which showed a typical dose‐dependent inhibition. The three anti‐CD40 mAbs from different sources had different effects. One mAbs potently inhibited both human and monkey B‐cell proliferation, whereas the other two mAbs exhibited strong or moderate inhibitory effects on human B‐cell proliferation but had little inhibitory effect on monkey B‐cell proliferation.

Conclusion

We have successfully established a modified CD40L‐activated B‐cell proliferation model for the in vitro evaluation of CD40‐CD154 pathway inhibitors, which may provide important evidence for the selection of appropriate therapeutic antibodies and their dose determination for xenotransplantation.
Transcendence of Hecke–Mahler series
Authors: Luca Florian , Ouaknine Joël , Worrell James
Published: February 2025

We prove transcendence of the Hecke–Mahler series , where is a non‐constant polynomial, is a real number, is an irrational real number and is an algebraic number such that .
Modulation of cardiomyocyte contractility and action potentials with chemogenetic chloride currents
Authors: Sönmez Muhammed , Stüdemann Tim , Manthey Christoph , Covic Anita , Shehata Nancy , Im Junsoo , Schwarzova Barbora , Rössinger Judith , Srikantharajah Rajiven , Shibamiya Aya , Schwedhelm Edzard , Eschenhagen Thomas , Christ Torsten , Weinberger Florian
Published: February 2025

Transient perturbation of electrical activity is used in neuroscience to study the impact of specific neuronal cell populations on brain function. Similarly, cardiomyocyte (CM) physiology can be controlled by the activation of artificially expressed ion channels. Pharmacologically selective actuator modules (PSAMs) are engineered ligand‐gated ion channels that can be activated with small molecules. We aimed to use the ‘inhibitory’ PSAMs, (i) PSAML141F,Y115F‐GlyR (PSAM‐GlyR) and (ii) PSAML131G,Q139L,Y217F (ultrapotent PSAM4‐GlyR), which consist of modified α7‐nicotinergic acetylcholine receptor ligand binding domains and the ion pore domain of the glycine receptor, to modulate CM physiology with chloride currents. We employed CRISPR/Cas9 to integrate PSAM‐GlyR and PSAM4‐GlyR in induced pluripotent stem cells, differentiated CMs and generated engineered heart tissue (EHT). Video optical force recordings, sharp microelectrode action potential measurements and patch‐clamp technique were used to characterize PSAM‐GlyR and PSAM4‐GlyR CMs. PSAM‐GlyR and PSAM4‐GlyR activation allowed titration of chloride currents in a reversible manner. We found that chloride currents modulated action potential characteristics. Patch clamp recordings showed that channel activation resulted in chloride‐driven currents that depolarized the cell. In EHT, this resulted in a stop of contractility that was fully reversible after wash‐out. We provide a comprehensive characterization of the chemogenetic tools PSAM‐GlyR and PSAM4‐GlyR in CMs, demonstrating their utility to modulate CM activity in vitro (PSAM‐GlyR and PSAM4‐GlyR) but also potential for in vivo applications (PSAM4‐GlyR).

image

Key points

Pharmacologically selective actuator modules (PSAMs) are engineered ligand‐gated ion channels that can be activated with small molecules.

These chemogenetic tools have been applied in neuroscience to inhibit neuronal activity.

Chemogenetic tools can also be used to modulate cardiomyocyte physiology.

Activation of the PSAMs, PSAM‐GlyR and PSAM4‐GlyR depolarized cardiomyocytes and thus stopped cardiac contractility.

Our study characterizes novel tools that can be used to modulate cardiomyocyte physiology in vitro and in vivo.
Group Conditions and the Perpetrators of Evil: Colombian Armed Groups
Authors: Mirón Lourdes , Blanco Amalio , Davies-Rubio Amanda
Published: February 2025

Violent extremism of groups in armed conflicts is commonly affected by multiple psychological mechanisms and processes: leadership structure, tasks entrusted to each of its members, norms and sanctions, ideological indoctrination, etc. The presence of these components in extremely violent actions in the Colombian conflict was analyzed. All 18 participants (14 males and 4 females) were demobilized members of the Self-defense Forces of Colombia (Autodefensas Unidas de Colombia, AUC) and guerrilla organizations (FARC, ELN, among others) which had participated directly or indirectly in violent actions against people and groups (which include murder, torture, and massacres). A qualitative methodology was used, specifically in-depth interviews and content analysis. This analysis showed that Colombian armed groups are made up of people with different psychological characteristics and social backgrounds (age, sex, place of residence, socioeconomic status, ethnicity, etc.), but their integration into the armed conflict and the violent actions they carried out respond to specific conditions and structure of the group they belong to rather than to personal factors. The components of the group structure, rule compliance, entrusted task performance and obedience to the orders of authority are the main reasons for the violent extremism that has characterized the activities of these people.
A material removal rate prediction model for high-shear and low-pressure grinding of single crystal silicon
Authors: Tian Yebing , Zhao Shuangchen , Zhang Guoyu , Wang Pengzhan , Liu Shuang
Published: February 2025

A novel abrasive tool, based on the principle of liquid body armor, was developed in previous study. However, a material removal rate (MRR) model for the high-shear and low-pressure grinding of brittle materials using this tool has yet to be established. Through the analysis of the contact mechanism, two critical transition depths and three distinct stages were identified. The acting force on an active abrasive grain and its corresponding depth of cut were also determined. The influence of various grinding parameters on the maximum undeformed chip thickness (MUCT) was analyzed. Subsequently, an MRR prediction model was developed, incorporating the stress distribution at the contact interface. The effectiveness of this model was validated through high-shear and low-pressure grinding experiments. The predicted MRR values under different grinding parameters as normal force, grinding speed, and workpiece feed rate, showed a strong correlation with experimental results, with average prediction errors of 12.65%, 10.30%, and 8.70%, respectively.
Impact of Playing Middle and Side Pick-and-Roll Actions With Aggressive and Containing Defensive Strategies on Workload During Small-Sided Games in Male Basketball Players
Authors: Qarouach Abdelaziz , Matulaitis Kęstutis , Butautas Ramunas , Conte Daniele
Published: February 2025

Purpose: This study aimed to evaluate the effect of executing different pick-and-roll (PnR) actions and performing different defensive strategies on workloads during basketball small-sided games. Methods: Twelve male basketball players (age: 21 [3] y; stature: 192 [5] cm; body mass: 84 [9] kg) completed 4 randomized small-sided games including PnRs executed on 2 court positions (ie, middle and side PnR) and 2 defensive strategies (ie, aggressive [ie, trap] and containing [ie, drop and ice for middle and side PnR, respectively] strategy). PlayerLoad and number of accelerations, decelerations, and changes of direction are classified as low (<2.5 m·s−2), medium (between 2.5 and 3.5 m·s−2), and high (>3.5 m·s−2), and jumps categorized as low (<40 cm) and high (≥40 cm) were used as external-load measures, while rating of perceived exertion was used as an internal-load measure. Results: Higher PlayerLoad values were found when playing middle PnR compared with side PnR (P = .046; effect size [ES] = 0.6; 95% CI, 0.0–1.2; moderate). Furthermore, trap defense showed moderately higher values of PlayerLoad (P < .001; ES = 1.1; 95% CI, 0.5–1.7), high accelerations (P = .006; ES = 0.8; 95% CI, 0.3–1.4), medium changes of direction (P = .047; ES = 0.6; 95% CI, 0.0–1.2), and high changes of direction (P = .050; ES = 0.6; 95% CI, 0.0–1.2) compared with drop and/or ice defense. No effects of court position and defensive strategy were found in rating of perceived exertion (P > .05). Conclusions: When planning small-sided games with tactical target, basketball coaches are advised to use middle PnR and aggressive defensive strategies to increase player’s external load compared with side PnR and containing defensive strategies.
Player Tracking, Shot Charts, and the National Basketball Association’s Three-Point Revolution: A Technology-Based Misspecification in a Primary Sport Management Setting?
Authors: Ehrlich Justin , Sanders Shane
Published: February 2025

Neoclassical economics holds that agents use resources to maximize objectives subject to constraints. Behavioral economics allows agents to engage in suboptimal decision making due to a host of cognitive biases. We test these theories in a prominent sport management setting. Many sports teams use management information systems to aid in multistream optimization tasks. We find that National Basketball Association team shot-selection tools—shot charts that do not account for shot-pursuant free-throw scoring—distort characterizations of optimal basketball shot selection (e.g., between two- and three-point attempts). Chart aggregations suggest a substantial, persistent three-point premium—continued gains from increases in three-point shooting volume. Through 2021–2022, teams have undertaken these increases, creating the National Basketball Association “Three-Point Revolution.” Using data science methods, we develop refined shot charts that consider shot-pursuant free-throw scoring. Accounting for this, the National Basketball Association has been in significant and widening three-point dispremium since 2018–2019.
Online Intervention Program Based on Need‐Supportive Activities to Promote Physical Activity and Cognitive Functions in Physical Education
Authors: Behzadnia Behzad , Leo Francisco M. , Khalilpourshiraz Zohreh , Karimi Amin
Published: February 2025

Purpose: We analyzed the effect of need-supportive activities intervention on students’ psychological needs, motivation, physical activity behaviors, and cognitive functions in online physical education during the COVID-19 outbreak. Method: A total of 495 secondary students (Mage = 15.54, standard deviation = 1.05, females = 50.7), and eight physical education teachers (ages ranging from 26 to 38 years old) participated in this quasi-experimental research. The present study featured two conditions: need-supportive activities intervention experimental and no-intervention control conditions, and measurements were taken at three time points. Results: Compared with students in the control condition, students in the experimental condition reported higher autonomous motivation (T2: MΔ = 0.28, p = .006; T3: MΔ = 0.27, p = .02) and cognitive function (T2: MΔ = 0.27, p = .01; T3: MΔ = 0.26, p = .03) and lower amotivation (T2: MΔ = −0.32, p = .03; T3: MΔ = −0.40, p = .02), but we did not find differences on need satisfaction, need frustration, controlled motivation, and physical activity behaviors between the two conditions (p > .05). Conclusion: The findings showed that the need-supportive activities intervention could help students remain motivated toward activities during their leisure time and improve their cognitive functions in physical education.
Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer
Authors: Kim Seok-Young , de Weert Tamar A. E. , Vermeulen Marijn , Ringnalda Femke , Kester Lennart , Zsiros Jozsef , Eising Selma , Molenaar Jan J. , Sanders Karin , van de Wetering Marc , Clevers Hans
Published: February 2025

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor in adolescent and young adult patients. Now, there is no standard-of-care treatment for these patients. Reliable models that represent this disease and can be used for translational research are scarce. To model SCCOHTs, we have established eight patient-derived tumoroid lines from tumor lesions of three patients with SCCOHT. The tumoroids recapitulate genomic and transcriptomic characteristics of the corresponding patient tumors and capture intrapatient tumor heterogeneity. Organoid drug profiling using a library of 153 clinical compounds identified methotrexate as an effective and selective drug against SCCOHTs with a clinically relevant IC
50
of 35 nanomolars. RNA sequencing demonstrated that methotrexate induced TP53 pathway activation and apoptosis. These data underscore that organoid technology can support the design of therapeutic strategies for rare cancers.
DET1 dynamics underlie cooperative ubiquitination by CRL4
DET1-COP1
complexes
Authors: Burgess Abigail E. , Loughran Tarren A. , Turk Liam S. , Nyvall Hunter G. , Dunlop Jessica L. , Jamieson Sam A. , Curry Jack R. , Burke John E. , Filipcik Pavel , Brown Simon H. J. , Mace Peter D.
Published: February 2025

Transcription factor ubiquitination is a decisive regulator of growth and development. The DET1-DDB1-DDA1 (DDD) complex associates with the Cullin-4 ubiquitin ligase (CRL4) and a second ubiquitin ligase, COP1, to control ubiquitination of transcription factors involved in neurological, metabolic, and immune cell development. Here, we report the structure of the human DDD complex, revealing a specific segment of DET1 that can recruit ubiquitin-conjugating (E2) enzymes. Structural variability analysis, mass spectrometry, and mutagenesis based on AlphaFold predictions suggest that dynamic closure of DET1, stabilized by DDA1, underlies coordinated recruitment of E2 enzymes and COP1. Biochemical assays suggest that the E2 acts as a recruitment factor to bring COP1 to DET1 for more effective substrate ubiquitination, which parallels a catalytically inactive E2 enzyme (COP10) in plant DDD complexes. This work provides a clear architecture for regulation and cooperative CRL4
DET1-COP1
complex assembly, which can affect degradation of diverse targets by COP1 complexes.
Ambient outdoor heat and accelerated epigenetic aging among older adults in the US
Authors: Choi Eun Young , Ailshire Jennifer A.
Published: February 2025

Extreme heat is well-documented to adversely affect health and mortality, but its link to biological aging—a precursor of the morbidity and mortality process—remains unclear. This study examines the association between ambient outdoor heat and epigenetic aging in a nationally representative sample of US adults aged 56+ (
N
= 3686). The number of heat days in neighborhoods is calculated using the heat index, covering time windows from the day of blood collection to 6 years prior. Multilevel regression models are used to predict PCPhenoAge acceleration, PCGrimAge acceleration, and DunedinPACE. More heat days over short- and mid-term windows are associated with increased PCPhenoAge acceleration (e.g.,
B
prior7-dayCaution+heat
: 1.07 years). Longer-term heat is associated with all clocks (e.g.,
B
prior1-yearExtremecaution+heat
: 2.48 years for PCPhenoAge,
B
prior1-yearExtremecaution+heat
: 1.09 year for PCGrimAge, and
B
prior6-yearExtremecaution+heat
: 0.05 years for DunedinPACE). Subgroup analyses show no strong evidence for increased vulnerability by sociodemographic factors. These findings provide insights into the biological underpinnings linking heat to aging-related morbidity and mortality risks.
Constraining the entire Earth system projections for more reliable climate change adaptation planning
Authors: Li Chao , Zwiers Francis W. , Zhang Xuebin , Fischer Erich M. , Du Fujun , Liu Jieyu , Wang Jianyu , Liang Yongxiao , Li Tong , Yuan Lina
Published: February 2025

The warming climate is creating increased levels of climate risk because of changes to the hazards to which human and natural systems are exposed. Projections of how those hazards will change are affected by uncertainties in the climate sensitivity of climate models, among other factors. While the level-of-global-warming approach can circumvent model climate sensitivity uncertainties in some applications, practitioners faced with specific adaptation responsibilities often find such projections difficult to use because they generally require time-oriented information. Earth system projections following specified emissions scenarios can, however, be constrained by applying the level-of-global-warming approach to observationally constrained warming projections to yield more reliable time-oriented projections for adaption planning and implementation. This approach also allows individual groups to produce consistent and comparable assessments of multifaceted climate impacts and causal mechanisms, thereby benefiting climate assessments at national and international levels that provide the science basis for adaptation action.
Dimeric assembly of F
1
-like ATPase for the gliding motility of
Mycoplasma
Authors: Toyonaga Takuma , Kato Takayuki , Kawamoto Akihiro , Miyata Tomoko , Kawakami Keisuke , Fujita Junso , Hamaguchi Tasuku , Namba Keiichi , Miyata Makoto
Published: February 2025

Rotary ATPases, including F
1
F
O
-, V
1
V
O
-, and A
1
A
O
-ATPases, are molecular motors that exhibit rotational movements for energy conversion. In the gliding bacterium,
Mycoplasma mobile
, a dimeric F
1
-like ATPase forms a chain structure within the cell, which is proposed to drive the gliding motility. However, the mechanisms of force generation and transmission remain unclear. We determined the electron cryomicroscopy (cryo-EM) structure of the dimeric F
1
-like ATPase complex. The structure revealed an assembly distinct from those of dimeric F
1
F
O
-ATPases. The F
1
-like ATPase unit associated by two subunits GliD and GliE was named G
1
-ATPase as an R
1
domain of rotary ATPases. G
1
-β subunit, a homolog of the F
1
-ATPase catalytic subunit, exhibited a specific N-terminal region that incorporates the glycolytic enzyme, phosphoglycerate kinase into the complex. Structural features of the ATPase displayed strong similarities to F
1
-ATPase, suggesting a rotation based on the rotary catalytic mechanism. Overall, the cryo-EM structure provides insights into the mechanism through which G
1
-ATPase drives the
Mycoplasma
gliding motility.
Increased SARS-CoV-2 IgG4 has variable consequences dependent upon Fc function, Fc receptor polymorphism, and viral variant
Authors: Aurelia L. Carissa , Purcell Ruth A. , Theisen Robert M. , Kelly Andrew , Esterbauer Robyn , Ramanathan Pradhipa , Lee Wen Shi , Wines Bruce D. , Hogarth P. Mark , Juno Jennifer A. , Allen Lilith F. , Bond Katherine A. , Williamson Deborah A. , Trevillyan Janine M. , Trubiano Jason A. , Nguyen Thi HO , Kedzierska Katherine , Wheatley Adam K. , Kent Stephen J. , Arnold Kelly B. , Selva Kevin John , Chung Amy W.
Published: February 2025

Repeated mRNA COVID-19 vaccination increases spike-specific immunoglobulin G4 (IgG4) titers. Here, we characterized the influence of increased IgG4 titers on a range of Fc-mediated responses. Elevated spike-specific IgG4 reduced binding to FcγRIIIa and decreased antibody-dependent cellular cytotoxicity. However, in individuals with lower total spike-specific IgG, IgG4 acted in synergy with other IgG subclasses to improve FcγRI and FcγRIIa binding and consequently antibody-dependent cellular phagocytosis. Furthermore, this trend was more pronounced with more recent SARS-CoV-2 variants where vaccination induced comparably lower total spike-specific titers. These observations were further confirmed by in silico modeling where antibody subclass concentrations and FcγR polymorphisms were modulated. Collectively, we illustrate that the impact of elevated IgG4 titers upon Fc functions is dependent on multiple interconnected antibody and antigen factors, which should be taken into consideration when dissecting the mechanisms driving an effective Fc-mediated response following vaccination.
Correlated nanoimaging of structure and dynamics of cation-polaron coupling in hybrid perovskites
Authors: Wilcken Roland , Esses Branden L. , Nithyananda Kumar Rachith S. , Hurley Lauren A. , Shaheen Sean E. , Raschke Markus B.
Published: February 2025

Hybrid organic-inorganic perovskites exhibit high photovoltaic performance and other novel photonic functions. While polaron formation is believed to facilitate efficient carrier transport, the elementary processes of the underlying electron-lattice coupling are yet poorly understood because of the multiscale chemical and structural heterogeneities. Here, we resolve in combined ground- and excited-state spatiospectral ultrafast nanoimaging how structural characteristics are related to both molecular cation and polaron dynamics. We use the observed nanoscale spatial variations of the formamidinium (FA) cation transient vibrational blue shifts as a local probe of the nonlocal polaron-cation coupling. From the correlation with nanomovies of the polaron dynamics, we then infer how a softer more polarizable lattice supports stable polarons and longer-lived residual carriers. This, together with a relative intragrain homogeneity in contrast to high intergrain heterogeneity, suggests pathways for improved synthesis and device engineering, and that perovskite photonics performance is still far from any fundamental limits.
Cavity QED in a high NA resonator
Authors: Shadmany Danial , Kumar Aishwarya , Soper Anna , Palm Lukas , Yin Chuan , Ando Henry , Li Bowen , Taneja Lavanya , Jaffe Matt , David Schuster , Simon Jon
Published: February 2025

From fundamental studies of light-matter interaction to applications in quantum networking and sensing, cavity quantum electrodynamics (QED) provides a toolbox to control interactions between atoms and photons. The coherence of interactions is determined by the single-pass atomic absorption and number of photon round-trips. Reducing the cavity loss has enabled resonators supporting 1 million roundtrips but with limited material choices and increased alignment sensitivity. Here, we present a high–numerical aperture, lens-based resonator that pushes the single-atom single-photon absorption probability near its fundamental limit, reducing the mode size at the atom to order λ. This resonator provides a single-atom cooperativity of 1.6 in a cavity where the light circulates ∼10 times. We load single
87
Rb atoms into this cavity, observe strong coupling, and demonstrate cavity-enhanced atom detection with fidelity of 99.55(6)% and survival of 99.89(4)% in 130 μs. Introducing intracavity imaging systems will enable cavity arrays compatible with Rydberg atom array computing technologies, expanding the applicability of the cavity QED toolbox.
The inner core enables transient touch detection in the Pacinian corpuscle
Authors: Ziolkowski Luke H. , Nikolaev Yury A. , Chikamoto Akitoshi , Oda Mai , Feketa Viktor V. , Monedero-Alonso David , Ardasheva Serafima A. , Bae Samuel S. , Xu C. Shan , Pang Song , Gracheva Elena O. , Bagriantsev Sviatoslav N.
Published: February 2025

Pacinian corpuscles detect transient touch and vibration in vertebrates. Corpuscles are composed of a mechanoreceptor afferent surrounded by lamellar Schwann cells (LSCs), enclosed by a multilayered outer core. The spatial arrangement of these components and their contribution to sensory tuning are unclear. We report the three-dimensional architecture of the Pacinian corpuscle and reveal the role of its cellular components in touch detection. In the prevailing model, the outer core acts as a mechanical filter that limits static and low-frequency stimuli from reaching the afferent terminal—the presumed sole site of touch detection. We show that the outer core is dispensable for the sensory tuning to transient touch and vibration; instead, these properties arise from the inner core. By acting as additional touch sensors, LSCs potentiate mechanosensitivity of the terminal, which detects touch via fast inactivating ion channels. Thus, functional tuning of the Pacinian corpuscle is enabled by an interplay between mechanosensitive LSCs and the afferent terminal in the inner core.
Textured lithium ceramics prepared by gas-solid reactive sintering
Authors: Zhang Xinshui , Yang Yihang , Hao Ruixin , Zhang Yue , Hu Xiangchen , Shi Hongsheng , Yang Zheyu , Yu Jiameng , Chen Xin , Zhang Chang , Yu Na , Gao Tianyi , Wei Ran , Zhang Zhenbo , Yu Yi , Liu Wei
Published: February 2025

Textured ceramics with anisotropic ionic conductivity are poised to establish superior ion transport pathways in solid-state electrochemical devices. However, their preparation methods remain a challenge. Here, we develop a gas-solid reactive sintering technique that successfully fabricates a variety of textured lithium ceramics, including electrolyte and electrode materials. These textured lithium ceramic electrolytes exhibit large columnar grains perpendicular to the surface. The textured electrodes indicate an out-of-plane crystallographic texture. As a result, the Li-ion transport pathways across the grain boundary plane are avoided in the textured lithium ceramic with low tortuosity, resulting in great ionic conductivity enhancement by 42 times compared to its traditional equiaxed counterpart. In addition, both Monte Carlo simulation and finite element analysis support the experimental results. This innovative gas-solid reactive sintering technique can extend to prepare various structured and functional ceramics with tailored structures and properties.
A springtail-inspired multimodal walking-jumping microrobot
Authors: Ramirez Serrano Francisco , Hyun Nak-seung Patrick , Steinhardt Emma , Lechère Pierre-Louis , Wood Robert J.
Published: February 2025

Although legged robots have demonstrated effective mobility in some natural settings, as robot size decreases, obstacles in their environment become challenging to overcome. Small arthropods scale obstacles many times their size through jumps powered by mechanisms that overcome speed and power limitations of muscle alone. The motivation for this study was to explore the marriage of impulsive (jumping) and nonimpulsive (cyclic legged ambulation) behaviors in a centimeter-scale robot. Here, jumping is achieved by striking the ground with a bioinspired appendage connected to a parallel linkage. As the linkage configuration passes through the singularity, a torque reversal occurs whereby elastic energy slowly stored by force-dense velocity-limited shape memory alloy actuators is rapidly released. A passively driven elastic hinge is introduced in the striking arm to mediate ground contact forces and direct jumping. High-speed video recording of the 14-millisecond launch phase reveals previously undocumented takeoff dynamics closely resembling those of springtails. A dynamic model was derived, and an experimentally validated simulation was used to optimize the design of key components. The 2.2-gram, 6.1-centimeter-long mechanism achieved a maximum horizontal jumping distance of 1.4 meters (23 body lengths), surpassing that of similarly sized insects. The mechanism was integrated with an agile quadrupedal microrobot with leg articulation suitable to achieve the ideal jumping posture. The platform demonstrated repeatable directional takeoffs and upright landings, enabling complex maneuvers to overcome obstacles and gaps. Last, we used this bioinspired robot to offer reflection on hypotheses related to springtail jumping behavior.
Virtual elasto-plastic robot compliance to active environments
Authors: Panzirsch Michael , Singh Harsimran , Wu Xuwei , Iskandar Maged , Koepken Anne , Luz Rute , Batti Nesrine , Lay Florian S. , Manaparampil Ajithkumar Narayanan , Mayershofer Luisa , Luo Xiaozhou , Burger Robert , Bustamante-Gomez Samuel , Butterfass Jörg , den Exter Emiel , Friedl Werner , Gumpert Thomas , Pavelski Pedro , Quere Gabriel , Schmidt Florian , Albu-Schaeffer Alin , Bauer Adrian S. , Leidner Daniel , Schmaus Peter , Hagengruber Annette , Krueger Thomas , Vogel Jörn , Lii Neal Y.
Published: February 2025

Humans exhibit a particular compliant behavior in interactions with their environment. Facilitated by fast physical reasoning, humans are able to rapidly alter their compliance, enhancing robustness and safety in active environments. Transferring these capabilities to robotics is of utmost importance particularly as major space agencies begin investigating the potential of cooperative robotic teams in space. In this scenario, robots in orbit or on planetary surfaces are meant to support astronauts in exploration, maintenance, and habitat building to reduce costs and risks of space missions. A major challenge for interactive robot teams is establishing the capability to act in and interact with dynamic environments. Analogous to humans, the robot should be not only particularly compliant in case of unexpected collisions with other systems but also able to cooperatively handle objects requiring accurate pose estimation and fast trajectory planning. Here, we show that these challenges can be attenuated through an enhancement of active robot compliance introducing a virtual plastic first-order impedance component. We present how elasto-plastic compliance can be realized via energy-based detection of active environments and how evasive motions can be enabled through adaptive plastic compliance. Two space teleoperation experiments using different robotic assets confirm the potential of the method to enhance robustness in interaction with articulated objects and facilitate robot cooperation. An experiment in a health care facility presents how the same method analogously solidifies robotic interactions in human-robot shared environments by giving the robot a subordinate role.
Reduced cerebellar rhythm by climbing fiber denervation is linked to motor rhythm deficits in mice and ataxia severity in patients
Authors: Lin Chih-Chun , Fang Ke-Chu , Balbo Ilaria , Liang Ting-Yu , Liu Chia-Wei , Liu Wen-Chuan , Wang Yi-Mei , Hung Yen-Ling , Yang Kai-Chien , Geng Scott Kun , Ni Chun-Lun , Driscoll Christopher P. , Ruff David S. , Kumar Ami , Amokrane Nadia , Desai Natasha , Faust Phyllis L. , Louis Elan D. , Kuo Sheng-Han , Pan Ming-Kai
Published: February 2025

Cerebellar ataxia results from various genetic and nongenetic disorders and is characterized by involuntary movements that impair precision and motor rhythm. Here, we report that climbing fiber (CF) denervation is a common pathophysiology underlying motor rhythm loss in cerebellar ataxia. By examining cerebellar pathology in patients with spinocerebellar ataxia (SCA) types 1, 2, and 6 and multiple system atrophy, we identified CF degeneration with synaptic loss as a shared pathophysiology. Optogenetic silencing of CF synaptic activity in mice induced ataxia-like motor dysfunctions and loss of motor precision. In addition, CF silencing resulted in cerebellar and motor rhythm loss, another core feature of ataxia. This rhythm loss was predominantly CF dependent and resistant to Purkinje cell–specific lesioning by diphtheria toxin. Correspondingly, two patients with inferior olive pathology, the brain site that provides CFs to Purkinje cells, presented with ataxia and cerebellar rhythm loss. Patients with genetic or nongenetic cerebellar ataxia exhibited cerebellar rhythm loss that correlated with the Scale for the Assessment and Rating of Ataxia. Chemogenetic stimulation of CFs improved cerebellar and motor rhythms as well as motor performance in the SCA type 1 mouse model of ataxia. These results suggest that CF-dependent cerebellar rhythm loss occurs across different types of cerebellar ataxia, contributing to motor imprecision and motor rhythm loss, two defining features of ataxia.
BCKDHA-BCKDHB
digenic gene therapy restores metabolic homeostasis in two mouse models and a calf with classic maple syrup urine disease
Authors: Wang Jiaming , Poskitt Laura E. , Gallagher Jillian , Puffenberger Erik G. , Wynn R. Max , Shishodia Gauri , Chuang David T. , Beever Jonathan , Hardin Donald L. , Brigatti Karlla W. , Baker William C. , Gately Rachael , Bertrand Stephanie , Rodrigues Ashlin , Benatti Hector R , Taghian Toloo , Hall Erin , Prestigiacomo Rachel , Liang Jialing , Chen Gong , Zhou Xuntao , Ren Lingzhi , Liu Nan , He Ran , Su Qin , Xie Jun , Jiang Zhong , Gruntman Alisha , Gray-Edwards Heather , Gao Guangping , Strauss Kevin A. , Wang Dan
Published: February 2025

Classic maple syrup urine disease (MSUD) results from biallelic mutations in genes that encode the
branched-chain α-ketoacid dehydrogenase E1
α (
BCKDHA
),
E1
β (
BCKDHB
), or
dihydrolipoamide branched-chain transacylase
(
DBT
) subunits, which interact to form the mitochondrial BCKDH complex that decarboxylates ketoacid derivatives of leucine, isoleucine, and valine. MSUD is an inborn error of metabolism characterized by recurrent life-threatening neurologic crises and progressive brain injury that can only be managed with an exacting prescription diet or allogeneic liver transplant. To develop a gene replacement therapy for MSUD, we designed a dual-function recombinant adeno-associated virus serotype 9 (rAAV9) vector to deliver codon-optimized
BCKDHA
and
BCKDHB
(rAAV9.h
A
-BiP-h
B
) to the liver, muscle, heart, and brain. rAAV9.h
A
-BiP-h
B
restored coexpression of BCKDHA and BCKDHB as well as BCKDH holoenzyme activity in

BCKDHA
−/−

HEK293T cells and did not perturb physiologic branched-chain amino acid homeostasis in wild-type mice at a systemic dose of 2.7 × 10
14
vector genomes per kilogram. In two models of severe MSUD (

Bckdha
−/−

and

Bckdhb
−/−

mice) and a newborn calf homozygous for
BCKDHA
c.248C>T, one postnatal injection prevented perinatal death, normalized growth, restored coordinated expression of BCKDHA and BCKDHB in the skeletal muscle, liver, heart, and brain, and stabilized MSUD biomarkers in the face of high protein ingestion. In summary, we developed a one-time
BCKDHA-BCKDHB
systemic dual-gene replacement strategy that holds promise as a therapeutic alternative to prescription diet and liver transplant for treatment of MSUD types 1A and 1B, the two most common forms of MSUD in humans.