bluuebunny/crossref_metadata_2025 huggingface dataset:
The consistent anti-cancer effect of a simple exercise (Ou MC decrescendo phenomenon exercise) may hold promise for low-cost cancer prevention
Authors: Ou Ming Cheh , Chen Fu Min
Published: February 2024

The causal relationship between physical activity and anti-cancer effect are not proved by the current studies. However, Ou MC decrescendo phenomenon treatment (OuDPt), a simple exercise treatment, has shown consistent anti-cancer effects, which evinces the consequent anti-cancer effect by physical activity. The anti-cancer effects through OuDPt in the context of physical activity and human body anatomical axes showed to induce apoptosis, restore apical-basal polarity of cancer cells and mitigate epithelial-mesenchymal transition (EMT) with concomitant clinical regression of uterine endometrial cancer, suppression of ovarian and pancreatic cancer growth, regression of early suspicious pancreatic cancer, enhancement of chemotherapy effect of pancreatic cancer and cessation of cancer-related bleeding, which underlines the most important anti-cancer mechanisms. Though such anti-cancer effects by OuDPt show insufficient efficacy for advanced cancer in long term treatment, OuDPt may be availed as an Ou MC decrescendo phenomenon exercise for cancer prevention. Further study is warranted.
Incomplete Fractures of Distal Long Bones Among Children in Early Stages of Mobility
Authors: Hughes Garza Holly , Zai Qais , Shanghvi Dhvani , Lawson Karla A. , Souder Christopher D.
Published: February 2024

Objectives

This study aimed to describe the characteristics, reported mechanism of injury, fracture morphology, and level of physical abuse concern among children in the early stages of mobility diagnosed with an incomplete distal extremity long bone fracture.

Methods

A retrospective chart review was performed for all children aged 10 to 12 months with an incomplete fracture of a distal forearm or distal lower limb who were reportedly pulling up, cruising, or ambulating, and who were evaluated by the child abuse pediatrics team at a single pediatric level I trauma center.

Results

Of the 29 patients who met inclusion criteria, the child abuse pediatrics team had concerns about physical child abuse for 3 children. Not every case with an unknown or discrepant history of injury was deemed concerning for abuse, but all 3 for whom the team determined that concern was warranted had an unknown or discrepant history. All 3 of these children had distal forearm fractures; 1 child had multiple concomitant fractures (including a scapular fracture), and 2 had evidence of bone healing at initial presentation. Each of these observations raises concern for abusive injury based on current evidence. Both-bone buckle fractures of the radius/ulna and tibia/fibula were the most common type of incomplete distal fracture.

Conclusions

This age group presents a unique challenge when designing evidence-based algorithms for the detection of occult injuries in emergency departments. Incomplete fractures of a distal limb are commonly related to a fall and may be considered “low specificity” for physical abuse. However, some publications conclude they should prompt universal physical abuse screening. Our small study indicated that the presence or absence of certain risk factors may provide additional information which could help guide the need for a more thorough evaluation for occult injury in early-mobile children with incomplete distal extremity long bone fractures. Ongoing research is warranted.
Developing and Investigating a Nanovibration Intervention for the Prevention/Reversal of Bone Loss Following Spinal Cord Injury
Authors: Williams Jonathan A. , Campsie Paul , Gibson Richard , Johnson-Love Olivia , Werner Anna S. , Sprott Mark , Meechan Ryan , Huesa Carmen , Windmill James F.C. , Purcell Mariel , Coupaud Sylvie , Dalby Matthew J. , Childs Peter G. , Riddell John S. , Reid Stuart
Published: February 2024

Osteoporosis disrupts the fine-tuned balance between bone formation and resorption leading to reductions in bone quantity and quality, ultimately leading to increased fracture risk. Prevention and treatment of osteoporotic fractures is essential, for reductions in mortality, morbidity and the economic burden, particularly considering the ageing global population. Extreme bone loss that mimics time-accelerated osteoporosis develops in the paralysed limbs following complete spinal cord injury (SCI).In vitronanoscale vibration (1 kHz, 30- or 90 nm amplitude) has been shown to drive differentiation of mesenchymal stem cells towards osteoblast-like phenotypes, enhancing osteogenesis, and inhibiting osteoclastogenesis, simultaneously. Here we develop and characterise a wearable device designed to deliver continuous nano-amplitude vibration to the hindlimb long bones of rats with complete SCI. We investigate whether a clinically feasible dose of nanovibration (4-hours/day, 5-days/week for 6 weeks) is effective at reversing the established SCI-induced osteoporosis. Laser interferometry and finite element analysis confirmed transmission of nanovibration into the bone, and micro-computed tomography and serum bone formation and resorption markers assessed effectiveness. The intervention did not reverse SCI-induced osteoporosis. However, serum analysis indicated an elevated concentration of the bone formation marker procollagen type 1 N-terminal propeptide (P1NP) in rats receiving 40 nm amplitude nanovibration, suggesting increased synthesis of type 1 collagen, the major organic component of bone. Therefore, enhanced doses of nanovibrational stimulus may yet prove beneficial in attenuating/reversing osteoporosis, particularly in less severe forms of osteoporosis.
Named Entity Recognition of Pharmacokinetic parameters in the scientific literature
Authors: Hernandez Ferran Gonzalez , Nguyen Quang , Smith Victoria C. , Cordero José Antonio , Ballester Maria Rosa , Duran Màrius , Solé Albert , Chotsiri Palang , Wattanakul Thanaporn , Mundin Gill , Lilaonitkul Watjana , Standing Joseph F. , Kloprogge Frank
Published: February 2024

The development of accurate predictions for a new drug’s absorption, distribution, metabolism, and excretion profiles in the early stages of drug development is crucial due to high candidate failure rates. The absence of comprehensive, standardised, and updated pharmacokinetic (PK) repositories limits pre-clinical predictions and often requires searching through the scientific literature for PK parameter estimates from similar compounds. While text mining offers promising advancements in automatic PK parameter extraction, accurate Named Entity Recognition (NER) of PK terms remains a bottleneck due to limited resources. This work addresses this gap by introducing novel corpora and language models specifically designed for effective NER of PK parameters. Leveraging active learning approaches, we developed an annotated corpus containing over 4,000 entity mentions found across the PK literature on PubMed. To identify the most effective model for PK NER, we fine-tuned and evaluated different NER architectures on our corpus. Fine-tuning BioBERT exhibited the best results, achieving a strictF1score of 90.37% in recognising PK parameter mentions, significantly outperforming heuristic approaches and models trained on existing corpora. To accelerate the development of end-to-end PK information extraction pipelines and improve pre-clinical PK predictions, the PK NER models and the labelled corpus were released open source athttps://github.com/PKPDAI/PKNER.
“Go and bring your husband”: a COM-B guided qualitative study on the barriers to male involvement in antenatal care in Bamenda Health District, Cameroon
Authors: Foglabenchi Lily Haritu , Marchant Tanya , Stöckl Heidi
Published: February 2024

Background

Increasing access to and utilization of skilled care during pregnancy and child birth can significantly reduce maternal and infant morbidity and mortality. Male involvement can positively influence utilization but resource limited settings like Cameroon encounter obstacles in engaging men in maternal and child health services. The aim of our study was to identify contextually relevant barriers to male involvement in antenatal care attendance to inform the development of an intervention that is aimed at promoting male involvement in maternal and child health in Cameroon.

Methods

This study used a qualitative design with qualitative methods that draw on 68 semi-structured interviews and three focus group discussions with pregnant women, male partners and health workers. Both interviews and group discussions were audio-recorded, transcribed. Guided by the Capability, Opportunity and Motivation (COM-B) model of behaviour and Theoretical Domains Framework (TDF), we analyzed data using directed content analysis, followed by inductive thematic analysis.

Results

Our findings suggest that male involvement in antenatal attendance in Bamenda Health District is under the influence of six multidimensional factors: limited awareness on the need for male involvement, limited female agency to engage men on ANC, maternal extortion, restrictive gender and socio-cultural norms regarding male ANC attendance, limited engagement of men by ANC staff and intrapersonal fears that fuel the avoidance of antenatal clinics. These overlapped across all three COM-B constructs, and 9 TDF. Overall, we noted that the motivation of male partners to participate in antenatal attendance is strongly influenced by social opportunity factors categorised as restrictive gender, social and cultural norms on male ANC attendance and psychosocial capability underpinned by limited health system engagement and awareness of male role in antenatal care.

Conclusions

This study identified multi-dimensional barriers related to male partner capability, opportunity and motivation to participate in antenatal care services. There is a need for interventions that employ gender-transformative approaches to adapt the socio-cultural environment and the messaging on antenatal care for optimal male involvement and subsequently, better health outcomes for mothers and children in Cameroon.
Thermo-amplifier circuit in probioticE. colifor stringently temperature-controlled release of a novel antibiotic
Authors: Dey Sourik , Seyfert Carsten E. , Fink-Straube Claudia , Kany Andreas M. , Müller Rolf , Sankaran Shrikrishnan
Published: February 2024

Peptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use. A key advantage of this technology is the possibility to control drug delivery within the body in real time using genetic switches. However, the performance of such genetic switches suffers when used to control drugs that require post-translational modifications or are toxic to the host. In this study, these challenges were experienced when attempting to establish a thermal switch for the production of a ribosomally synthesized and post-translationally modified peptide antibiotic, darobactin, in probioticE. coli. These challenges were overcome by developing a thermo-amplifier circuit that combined the thermal-switch with a T7 RNA Polymerase and its promoter that overcame limitations imposed by the host transcriptional machinery due to its orthogonality to it. This circuit enabled production of pathogen-inhibitory levels of darobactin at 40°C while maintaining leakiness below the detection limit at 37°C. More impressively, the thermo-amplifier circuit sustained production beyond the thermal induction duration. Thus, raised temperature for 2 h was sufficient for the bacteria to produce pathogen-inhibitory levels of darobactin even in the physiologically relevant simulated conditions of the intestines that include bile salts and low nutrient levels.

Graphical Abstract
Uncovering the simple adhesive strategy of the Toxoplasma parasite for high-speed motility
Authors: Vigetti Luis , Touquet Bastien , Debarre Delphine , Rose Thierry , Bureau Lionel , Abdallah Dima , Dubacheva Galina V. , Tardieux Isabelle
Published: February 2024

Toxoplasma gondiiis a protozoan parasite that has evolved a developmental morphotype called tachyzoite that navigates between cells and moves in and out of them in a wide repertoire of homeothermic hosts. Relying on a uniquely constant apicobasal bipolarity coupled to an actomyosin-driven retrograde surface flow, the tachyzoite has elaborated a molecular machinery to assemble transient anchoring contacts with the environment, which support the traction force required to power a typical helical gliding motility. Combining micropatterning with live, reflection interference contrast and expansion microscopies, we bring first nanoscale evidence that the tachyzoite needs to build only one apical anchoring contact with the substrate, thus spatially defining a minimal force transmission platform over which it can slide. We uncover that the apicobasal driven surface flow is set up in response to extracellular biochemical cues independent of adhesin release and tachyzoite-surface interactions, hence prior to motile activity. Furthermore, to identify the minimal adhesion requirements for helical gliding at the level of individual molecular species, we combine biochemical and biophysical quantitative assays based on tunable surface chemistry and quartz crystal microbalance with dissipation monitoring. These approaches uncover that glycosaminoglycan (GAG)-parasite interactions are sufficient to promote a productive contact for helical gliding and pave the way for the characterization of the structure and density of the molecules functionally engaged at this essential parasite-substrate mechanosensitive interface.
WITHDRAWN: Truncated NLRC5 isoforms in human placenta: expression, regulation by miR-218-5p, and function in trophoblasts
Authors: Shan Yanan , O’Brian Jacob A , Nadeem Lubna , Dunk Caroline , Chen Yan , Brkic Jelena , Hayder Heyam , Lye Stephen J , Peng Chun
Published: February 2024

Withdraw statement

The authors have withdrawn this manuscript because [the current results no longer support the conclusion in the article]. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Feature pre-selection for the development of epigenetic biomarkers
Authors: Cheng Yipeng , Gieger Christian , Campbell Archie , McIntosh Andrew M , Waldenberger Melanie , McCartney Daniel L , Marioni Riccardo E , Vallejos Catalina A
Published: February 2024

Over the last decade, a plethora of blood-based DNA methylation biomarkers have been developed to track differences in ageing, lifestyle, health, and biological outcomes. Typically, penalised regression models are used to generate these predictors, with hundreds or thousands of CpGs included as potential features. However, in such ultra high-dimensional settings, the effectiveness of these methods may be reduced.

Here, we introduce Related Trait-based Feature Screening (RTFS), a method for performing CpG pre-selection for incident disease prediction models by utilising associations between CpGs and health-related continuous traits. In a comparison with commonly used CpG pre-selection methods, we evaluate resulting downstream Cox proportional-hazards prediction models for 10-year type 2 diabetes (T2D) onset risk in Generation Scotland (n=18,414). The top performing models utilised incident T2D EWAS (AUC=0.881, PRAUC=0.279) and RTFS (AUC=0.877, PRAUC=0.277). The resulting models also improve prediction over a model using standard risk factors only (AUC=0.841, PRAUC=0.194) and replication was observed in the German-based KORA study (n=4,261)

RTFS is a flexible and generalisable framework that can help to refine biomarker development for incident disease outcomes.
North-south pathways, emerging variants, and high climate suitability characterize the recent spread of dengue virus serotypes 2 and 3 in the Dominican Republic
Authors: Miguel Isaac , Feliz Edwin P. , Agramonte Robinson , Martinez Pedro V. , Vergara Carlos , Imbert Yvonne , De la Cruz Lucia , de Castro Nurys , Cedano Odalis , De la Paz Yamilka , Fonseca Vagner , Santiago Gilberto A. , Muñoz-Jordán Jorge L. , Peguero Armando , Paulino-Ramírez Robert , Grubaugh Nathan D. , de Filippis Ana Maria Bispo , Alcantara Luiz Carlos Junior , Rico Jairo Mendez , Lourenço José , Franco Leticia , Giovanetti Marta
Published: February 2024

We employ a multidisciplinary approach, integrating genomics and epidemiology, to uncover recent dengue virus transmission dynamics in the Dominican Republic. Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures. These findings provide information for targeted interventions and resource allocation, informing as well towards preparedness strategies for public health agencies in mitigating climate and geo-related dengue risks.
Cleft lip sidedness and the association with additional congenital malformations
Authors: Fell Matthew , Fitzsimons Kate J , Hamilton Mark J , Medina Jibby , Butterworth Sophie , Park Min Hae , Van der Meulen Jan , Lewis Sarah , Chong David , Russell Craig JH
Published: February 2024

Objective

To investigate the association between the sidedness of orofacial clefts and additional congenital malformations.

Design

Linkage of a national registry of cleft births to national administrative data of hospital admissions

Setting

National Health Service, England

Participants

2,007 children born with cleft lip +-alveolus (CL+-A) and 2,724 with cleft lip and palate (CLP) born between 2000 and 2012.

Main outcome measure

The proportion of children with ICD-10 codes for additional congenital malformations by the sidedness (left, right or bilateral) of orofacial clefts.

Results

For CL+-A phenotypes, there was no evidence for a difference in the prevalence of additional anomalies between left (22%, reference), right (22%, aOR 1.02, 95% CI 0.80 to 1.28; p= 0.90) and bilateral clefts (23%, aOR 1.09, 95% CI 0.75 to 1.57; p= 0.66). For CLP phenotypes, there was evidence of a lower prevalence of additional malformations in left (23%, reference) compared to right (32%, aOR 1.54, 95% CI 1.25 to 1.91; p <0.001) and bilateral clefts (33%, aOR 1.64, 95% CI 1.35 to 1.99; p<0.001).

Conclusions

The prevalence of additional congenital malformations was similar across sidedness subtypes with CL+-A phenotypes but was different for sidedness subtypes within CLP cases. These data support the hypothesis that CL+-A has a different underlying aetiology from CLP and that within the CLP phenotype, right sided CLP may lie closer in aetiology to bilateral CLP than it does to left sided CLP.
Evaluating Knowledge Fusion Models on Detecting Adverse Drug Events in Text
Authors: Wegner Philipp , Fröhlich Holger , Madan Sumit
Published: February 2024

Background

Detecting adverse drug events (ADE) of drugs that are already available on the market is an essential part of the pharmacovigilance work conducted by both medical regulatory bodies and the pharmaceutical industry. Concerns regarding drug safety and economic interests serve as motivating factors for the efforts to identify ADEs. Hereby, social media platforms play an important role as a valuable source of reports on ADEs, particularly through collecting posts discussing adverse events associated with specific drugs.

Methodology

We aim with our study to assess the effectiveness of knowledge fusion approaches in combination with transformer-based NLP models to extract ADE mentions from diverse datasets, for instance, texts from Twitter, websites like askapatient.com, and drug labels. The extraction task is formulated as a named entity recognition (NER) problem. The proposed methodology involves applying fusion learning methods to enhance the performance of transformer-based language models with additional contextual knowledge from ontologies or knowledge graphs. Additionally, the study introduces a multi-modal architecture that combines transformer-based language models with graph attention networks (GAT) to identify ADE spans in textual data.

Results

A multi-modality model consisting of the ERNIE model with knowledge on drugs reached an F1-score of 71.84% on CADEC corpus. Additionally, a combination of a graph attention network with BERT resulted in an F1-score of 65.16% on SMM4H corpus. Impressively, the same model achieved an F1-score of 72.50% on the PSYTAR corpus, 79.54% on the ADE corpus, and 94.15% on the TAC corpus. Except for the CADEC corpus, the knowledge fusion models consistently outperformed the baseline model, BERT.

Conclusion

Our study demonstrates the significance of context knowledge in improving the performance of knowledge fusion models for detecting ADEs from various types of textual data.

Author Summary

Adverse Drug Events (ADEs) are one of the main aspects of drug safety and play an important role during all phases of drug development, including post-marketing pharmacovigilance. Negative experiences with medications are frequently reported in textual form by individuals themselves through official reporting systems or social media posts, as well as by doctors in their medical notes. Automated extraction of ADEs allows us to identify these in large amounts of text as they are produced every day on various platforms. The text sources vary highly in structure and the type of language included which imposes certain challenges on extraction systems. This work investigates to which extent knowledge fusion models may overcome these challenges by fusing structured knowledge coming from ontologies with language models such as BERT. This is of great interest since the scientific community provides highly curated resources in the form of ontologies that can be utilized for tasks such as extracting ADEs from texts.
Co-occurring infections in cancer patients treated with checkpoint inhibitors significantly increase the risk of immune related adverse events
Authors: Makunts Tigran , Grabska Siranuysh , Grabski Hovakim , Abagyan Ruben
Published: February 2024

Therapeutic antibodies designed to target immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4 have been applied in the treatment of various tumor types, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating CD8 cytotoxic T-cells. Nevertheless, this unique targeted mode of action was found to be associated with a broader range of immune-related adverse events, irAEs, affecting multiple physiological systems. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatal consequences. In this study we investigated over eighty thousand adverse event reports of irAEs in patients treated with PD-1, PD-L1, and CTLA-4 inhibitors. FDA Adverse Event Reporting System MedWatch submissions were used as the data source. These therapeutics included pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab. The data analysis of these reports revealed a statistically significant association of immune related adverse events, including serious and life-threatening events in patients who experienced infectious disease during treatment. Additionally, the association trend was preserved across all the three classes of checkpoint inhibitors and each of the seven individual therapeutic agent cohorts.
Fibrinogen is the key factor associated with tremor relieve and recurrence in the ET patients subjected with unilateral MRgFUS thalamotomy
Authors: Lin Jiaji , Lu Haoxuan , Zhang Dekang , Bian Xianbing , Hu Jianxing , Pan Longsheng , Lou Xin
Published: February 2024

Objective

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy has been shown to be safe and effective to treat various types of tremor diseases, but whether the clinical status of these patients was involved was still unknown.

Methods

We retrospectively studied the tremor symptoms and clinical variables (at hospitalization) of 59 essential tremor (ET) patients subjected with MRgFUS thalamotomy. Patients were categorized by the short-term tremor relieve and tremor recurrence within 12 months. Multivariate logistic regression was used to screen independent factors and construct the nomograms. Additional fibrinogen knock-out mice were applied to establish ET mouse model induced by harmaline and the frequency and intensity of tremor were measured and analyzed using a force-plated accelerometer.

Results

It is found that 39 ET patients (66.102%) with significantly better efficiency in short-term tremor relieve (control ratio > 75%) at 1-month postoperatively, while nine ET patients (15.254%) experienced significant tremor recurrence within postoperative one-year. Multivariate analysis suggested fibrinogen (OR = 0.182, 95% CI = 0.042-0.796,) and monocyte count (OR = 0, 95% CI = 0-0.001) were independently associated with better short-term tremor relieve (>75%) at 1-month postoperatively. A total of nine ET patients (15.254%) experienced significant tremor recurrence. Admission systolic blood pressure (OR = 1.013, 95% CI = 1.010-1.062), hypertension comorbidity (OR = 2.163, 95% CI = 1.412-53.565) and fibrinogen (OR = 1.620, 95% CI = 1.047-24.376) independently contributed to tremor recurrence. The nomograms were established for better tremor relieve and tremor recurrence and have excellent performance as the AUCs were 0.829 and 0.853 (bootstrap repetition = 1000). Moreover, fibrinogen knock-out promoted a great suppression on maximum tremor motion power and overall tremor activity in ET tremor model (P< 0.001).

Conclusions

The study found that baseline fibrinogen is the key factor associated with tremor relieve and recurrence for patients subjected with MRgFUS thalamotomy. Preoperative evaluation of clinical factors has important predictive significance for short- and long-term postoperative outcomes for patients treated with MRgFUS thalamotomy.
Associations between cord serum antibodies against phosphorylcholine and bacterial infections in neonates: a prospective cohort study in singletons and twins
Authors: Chen Ruoqing , Zheng Yeqi , Tan Weiri , Wu Feng , Liang Hui , Chen Xi , Chen Youmei , Liu Xian , Fang Fang , Zhang Quanfu , Zhang Rui , Chen Xu
Published: February 2024

Background

Antibodies against phosphorylcholine (anti-PC) are reported to protect against infection. However, the association between cord serum anti-PC and bacterial infection in neonates is yet to be investigated. This study aimed to investigate these associations among both singletons and twins.

Methods

A total of 1007 neonates (329 singletons and 678 twins) within the hospital-based Shenzhen Baoan Birth & Twin cohort were included in this study. Levels of IgM anti-PC, IgG anti-PC, as well as IgM, IgG, and IgA in cord serum were measured by enzyme-linked immunosorbent assay. Diagnoses of bacterial infections were identified within 0-27 days after birth. Multivariable logistic regression with propensity score adjustment was performed to assess the associations between levels of antibodies and neonatal bacterial infections.

Results

The mean (standard deviation) levels of IgM and IgG anti-PC were 46.68 (14.15) ng/ml and 73.68 (30.44) ng/ml, respectively. Neonatal bacterial infections were diagnosed in 24 singletons (7.29%) and 48 twins (7.08%). A higher level of IgM anti-PC was associated with a lower risk of neonatal bacterial infections in the analyses of singletons (Odds ratio [OR]: 0.64, 95% confidence interval [CI]: 0.41-0.99) or discordant twin pairs (concerning bacterial infection) (OR: 0.44, 95% CI: 0.20-0.95). Statistically significant association was also shown for IgG among singletons and the first-born twins, but not for IgG anti-PC, IgM, or IgA.

Conclusion

A higher cord serum level of IgM anti-PC is associated with a lower risk of bacterial infections in neonates.

Key point

A higher level of IgM anti-PC in cord serum is associated with a lower risk of bacterial infection in both singleton and twin neonates.
In-situ architecture of the human prohibitin complex
Authors: Lange Felix , Ratz Michael , Dohrke Jan-Niklas , Wenzel Dirk , Ilgen Peter , Riedel Dietmar , Jakobs Stefan
Published: February 2024

Prohibitins are a highly conserved family of proteins that have been implicated in a variety of functions including mitochondrial stress signalling and housekeeping, cell cycle progression, apoptosis, lifespan regulation and many others1, 2. The human prohibitins PHB1 and PHB2 have been proposed to act as scaffolds within the mitochondrial inner membrane, but their molecular organisation remained elusive. Using an integrative structural biology approach combining quantitative Western blotting, cryo-electron tomography, subtomogram averaging and molecular modelling, we determined the molecular organisation of the human prohibitin complex within the mitochondrial inner membrane. The proposed bell-shaped structure consists of eleven alternating PHB1 and PHB2 molecules. This study reveals an average of about 43 prohibitin complexes per crista, covering 1-3 % of the cristae membranes. These findings provide a structural basis for understanding the functional contributions of prohibitins to the integrity and spatial organisation of the mitochondrial inner membrane.
Distribution of soil and clinicalBurkholderia pseudomalleiisolates in Myanmar by using MLST
Authors: Aung Nay Myo , Htut Kyaw Myo , Aung Han Tin , Thant Aye Min , Oo Khine Zaw , Su Khine Khine
Published: February 2024

Burkholderia pseudomalleican be identified as Gram-negative bacillus without spore-forming in an environment such as soil and stagnant water. Human factors and climate changes make the incidence of melioidosis higher. Soil with high moisture and clay-rich is a suitable residence forB. pseudomallei. Twenty-one isolates ofB. pseudomalleiwere collected and performed by multilocus sequence typing. Among them, eight novel sequence types (STs) ofB. pseudomalleiwere found, while the rest show known STs. Interestingly, ST 56 from two patients was identified as the same region, while ST 90 showed local and global distribution. Among six ST 90B. pseudomallei, the three isolates were from soil and patients. Clinical ST 90 isolates were traced in the same region as soil ST 90 isolates. Those isolates may correlate with each other by using multilocus sequence typing (MLST) cost-effectively. However, it still needs to prove its correct relatedness. This study pointed out the reasonable assumption ofBurkholderia pseudomalleifor local and global distribution in Myanmar.
Structural basis of Cdk7 activation by dual T-loop phosphorylation
Authors: Düster Robert , Anand Kanchan , Binder Sophie C. , Schmitz Maximilian , Gatterdam Karl , Fisher Robert P. , Geyer Matthias
Published: February 2024

Cyclin-dependent kinase 7 (Cdk7) occupies a central position in cell-cycle and transcriptional regulation owing to its function as both a CDK-activating kinase (CAK) and part of the general transcription factor TFIIH. Cdk7 forms an active complex upon association with Cyclin H and Mat1, and its catalytic activity is regulated by two phosphorylations in the activation segment (T loop): the canonical activating modification at T170 and another at S164. Here we report the crystal structure of the fully activated human Cdk7/Cyclin H/Mat1 complex containing both T-loop phosphorylations. Whereas pT170 coordinates a set of basic residues conserved in other CDKs, pS164 nucleates an arginine network involving all three subunits that is unique to the ternary Cdk7 complex. We identify differential dependencies of kinase activity and substrate recognition on individual phosphorylations within the Cdk7 T loop. The CAK function of Cdk7 is not affected by T-loop phosphorylation, whereas activity towards non-CDK substrates is increased several-fold by phosphorylation at T170. Moreover, dual T-loop phosphorylation at both T170 and S164 stimulates multi-site phosphorylation of transcriptional substrates—the RNA polymerase II (RNAPII) carboxy-terminal domain (CTD) and the SPT5 carboxy-terminal repeat (CTR) region. In human cells, Cdk7-regulatory phosphorylation is a two-step process in which phosphorylation of S164 precedes, and may prime, T170 phosphorylation. Thus, dual T-loop phosphorylation can regulate Cdk7 through multiple mechanisms, with pS164 supporting tripartite complex formation and possibly influencing Cdk7 processivity, while the canonical pT170 enhances kinase activity towards critical substrates involved in transcription.
RelQ-mediated alarmone signaling regulates growth, sporulation, and stress-induced biofilm formation inClostridioides difficile
Authors: Malik Areej , Oludiran Adenrele , Poudel Asia , Alvarez Orlando Berumen , Woodward Charles , Purcell Erin B.
Published: February 2024

The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signaling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival inClostridioides difficile, a biofilm- and spore-forming pathogen that causes resilient, highly recurrentC. difficileinfections. The role of the SR in other processes and the effectors by which it regulatesC. difficilephysiology are unknown.C. difficileRelQ is a clostridial alarmone synthetase. Deletion ofrelQdysregulatesC. difficilegrowth in unstressed conditions, affects susceptibility to antibiotic and oxidative stressors, and drastically reduces biofilm formation. While wild-typeC. difficiledisplays increased biofilm formation in the presence of sub-lethal stress, the ΔrelQstrain cannot upregulate biofilm production in response to stress. Deletion ofrelQslows spore accumulation in planktonic cultures but accelerates it in biofilms. This work establishes biofilm formation and sporulation as alarmone-mediated processes inC. difficileand reveals the importance of RelQ in stress-induced biofilm regulation.
A quantitative ultrastructural timeline of nuclear autophagy reveals a role for dynamin-like protein 1 at the nuclear envelope
Authors: Mannino Philip J. , Perun Andrew , Surovtsev Ivan V. , Ader Nicholas R. , Shao Lin , Rodriguez Elisa C. , Melia Thomas J. , King Megan C. , Lusk C. Patrick
Published: February 2024

Autophagic mechanisms that maintain nuclear envelope homeostasis are bulwarks to aging and disease. By leveraging 4D lattice light sheet microscopy and correlative light and electron tomography, we define a quantitative and ultrastructural timeline of nuclear macroautophagy (nucleophagy) in yeast. Nucleophagy begins with a rapid accumulation of the selective autophagy receptor Atg39 at the nuclear envelope and finishes in ∼300 seconds with Atg39-cargo delivery to the vacuole. Although there are several routes to the vacuole, at least one pathway incorporates two consecutive membrane fission steps: inner nuclear membrane (INM) fission to generate an INM-derived vesicle in the perinuclear space and outer nuclear membrane (ONM) fission to liberate a double membraned vesicle to the cytosol. ONM fission occurs independently of phagophore engagement and instead relies surprisingly on dynamin like 1 (Dnm1), which is recruited to sites of Atg39 accumulation by Atg11. Loss of Dnm1 compromises nucleophagic flux by stalling nucleophagy after INM fission. Our findings reveal how nuclear and INM cargo are removed from an intact nucleus without compromising its integrity, achieved in part by a non-canonical role for Dnm1 in nuclear envelope remodeling.
Chrono-optimization of influenza vaccine administration: A systematic review and meta-analysis
Authors: Vink Koen , Kusters Jeroen , Wallinga Jacco
Published: February 2024

Background

There is growing evidence that the strength of vaccine responses depends on the time of day of vaccine administration. This systematic review provides an overview of the literature regarding the effect of the timing of influenza vaccination on the vaccine response. To estimate the extent of this effect, we conducted a meta-analysis of randomized controlled trials (RCTs) in which antigen-specific antibody titers were monitored following either morning or afternoon administration of the influenza vaccine.

Methods and results

A systematic literature search identified five relevant studies that reported antigen-specific titers against multiple influenza vaccine strains after both morning and afternoon vaccination. Four of the five studies reported higher antibody titers for at least one vaccine strain following morning vaccination. Two RCTs were included in the meta-analysis, each of which reported the response to three vaccine strains, resulting in a total of six responses. The meta-analysis revealed that morning vaccination elicited a stronger antibody response than afternoon vaccination, with a pooled standardized mean difference (SMD) of 0.24 (95% CI=0.01–0.47). The between-study heterogeneity (I2=66%) was mainly due to the significantly 01greater effect of morning vaccination among adults aged 65 years or older than among adults aged 60 years or younger (SMD=0.32, 95% CI=0.21–0.43 versus SMD=0.00, 95% CI=−0.16–0.16, respectively).

Conclusion

Influenza vaccinations administered in the morning induced a stronger antibody response in adults aged 65 years or older, who represent a major target group for influenza vaccination programs. Therefore, chrono-optimization of influenza vaccination could offer a safe and simple strategy for enhancing vaccine effectiveness. The paucity of relevant studies suggests that accounting for the time of vaccine administration in future vaccination trials could provide valuable insights into the potential benefits of chrono-optimization strategies.
Long-distance optical-conveyor-belt transport of ultracold
Cs133
and
Rb87
atoms
Authors: Matthies Alex J. , Mortlock Jonathan M. , McArd Lewis A. , Raghuram Adarsh P. , Innes Andrew D. , Gregory Philip D. , Bromley Sarah L. , Cornish Simon L.
Published: February 2024

We report on the transport of a thermal cloud of ultracold cesium and rubidium atoms over about 37 cm in under 25 ms using an optical conveyor belt formed by two counterpropagating beams with a controllable frequency difference that generate a movable optical lattice. By carefully selecting the waists and focus positions, we are able to use two static Gaussian beams for the transport, avoiding the need for a Bessel beam or variable-focus lenses. We characterize the transport efficiency for both species, including a comparison of different transport trajectories, gaining insight into the loss mechanisms and finding the minimum jerk trajectory to be optimum. Using the optimized parameters, we are able to transport up to 7×106 cesium or rubidium atoms with an efficiency up to 75%. To demonstrate the viability of our transport scheme for experiments employing quantum gas microscopy, we produce Bose-Einstein condensates of either species after transport and present measurements of the simultaneous transport of both species.

Published by the American Physical Society
2024
Light-field ghost imaging
Authors: Paniate A. , Massaro G. , Avella A. , Meda A. , Pepe F.V. , Genovese M. , D'Angelo M. , Ruo-Berchera I.
Published: February 2024

Techniques based on classical and quantum correlations in light beams, such as ghost imaging, allow us to overcome many limitations of conventional imaging and sensing protocols. Despite their advantages, applications of such techniques are often limited in practical scenarios where the position and the longitudinal extension of the target object are unknown. In this work, we propose and experimentally demonstrate an imaging technique, named light-field ghost imaging, that exploits light correlations and light-field imaging principles to enable going beyond the limitations of ghost imaging in a wide range of applications. Notably, our technique removes the requirement to have prior knowledge of the object distance, allowing the possibility of refocusing in postprocessing, as well as performing three-dimensional imaging while retaining all the benefits of ghost imaging protocols.

Published by the American Physical Society
2024
Natural anomaly mediation from the landscape with implications for LHC SUSY searches
Authors: Baer Howard , Barger Vernon , Bolich Jessica , Dutta Juhi , Sengupta Dibyashree
Published: February 2024

Supersymmetric models with the anomaly-mediated supersymmetry (SUSY) breaking (AMSB) form for soft SUSY breaking terms arise in two different settings: (1) extra-dimensional models where SUSY breaking occurs in a sequestered sector, and (2) 4−d models with dynamical SUSY breaking in a hidden sector where scalars gain masses of order the gravitino mass m3/2, but gaugino masses and trilinear soft terms are assumed to be of the AMSB form. Both models run into serious conflicts with (1) LHC sparticle and Higgs mass constraints, (2) constraints from winolike weakly interacting massive particle dark matter searches, and (3) bounds from naturalness. These conflicts may be avoided by introducing minor changes to the underlying phenomenological models consisting of nonuniversal bulk scalar Higgs masses and A terms, providing a setting for natural anomaly mediation (nAMSB). In nAMSB, the wino is still expected to be the lightest of the gauginos, but the Higgsinos are expected to be the lightest electroweakinos (EWinos) in accord with naturalness. We examine what sorts of spectra are expected to emerge when nAMSB arises from a string landscape setting: While model 2 can only be natural for a Higgs mass mh≲123  GeV, model 1 can accommodate naturalness along with mh∼125  GeV while still respecting LHC bounds on sparticle masses. We explore the LHC phenomenology of nAMSB models where we find that for Higgsino pair production, typically larger dilepton mass gaps arise from the soft dilepton-plus-jets signature than in models with gaugino mass unification. For wino-pair production, the higher m3/2 portion of nAMSB parameter space is excluded by recent LHC bounds from gaugino pair production searches. We characterize the dominant LHC signatures arising from the remaining lower m3/2∼90–200  TeV range of parameter space, which should be fully testable at high-luminosity LHC via EWino pair production searches.

Published by the American Physical Society
2024
Explicit no-
π2
renormalization schemes in QCD at five loops
Authors: Gracey J. A.
Published: February 2024

We examine a variety of renormalization schemes in QCD based on its 3-point vertices where the β-functions, gluon, ghost, quark and quark mass anomalous dimensions in each scheme do not depend on ζ4 or ζ6 in an arbitrary linear covariant gauge at five loops. We comment on the C-scheme.

Published by the American Physical Society
2024
Emission of twisted photons by a Dirac electron in a strong magnetic field
Authors: Pavlov I. , Karlovets D.
Published: February 2024

We study the spontaneous emission of a photon during the transitions between relativistic Landau states of an electron in a constant magnetic field that can reach the Schwinger value of Hc=4.4×109  T. In contrast to the conventional method, in which detection of both the final electron and the photon are implied in a certain basis, here we derive the photon state as it evolves from the process itself. It is shown that the emitted photon state represents a twisted Bessel beam propagating along the field axis with a total angular momentum (TAM) projection onto this axis ℓ−ℓ′, where ℓ and ℓ′ are the TAM of the initial electron and of the final one, respectively. Thus, the majority of the emitted photons turn out to be twisted, with ℓ−ℓ′≳1, even when the magnetic field reaches the critical value of H∼Hc. The transitions without a change of the electron angular momentum, ℓ′=ℓ, are possible, yet much less probable. We also compare our findings with those for a spinless charged particle and demonstrate their good agreement for the transitions without change of the electron spin projection even in the critical fields, while the spin-flip transitions are generally suppressed. In addition, we argue that whereas the ambiguous choice of an electron spin operator affects the differential probability of emission, this problem can partially be circumvented for the photon evolved state because it is the electron TAM rather than the spin alone that defines the TAM of the emitted twisted photon.

Published by the American Physical Society
2024
Catalog of precessing black-hole-binary numerical-relativity simulations
Authors: Hamilton Eleanor , Fauchon-Jones Edward , Hannam Mark , Hoy Charlie , Kalaghatgi Chinmay , London Lionel , Thompson Jonathan E. , Yeeles Dave , Ghosh Shrobana , Khan Sebastian , Kolitsidou Panagiota , Vano-Vinuales Alex
Published: February 2024

We present a public catalog of numerical-relativity binary-black-hole simulations. The catalog contains datasets from 80 distinct configurations of precessing binary-black-hole systems, with mass ratios up to m2/m1=8, dimensionless spin magnitudes on the larger black hole up to |S→2|/m22=0.8 (the small black hole is nonspinning), and a range of five values of spin misalignment for each mass-ratio/spin combination. We discuss the physical properties of the configurations in our catalog, and assess the accuracy of the initial configuration of each simulation and of the gravitational waveforms. We perform a careful analysis of the errors due to the finite resolution of our simulations and the finite distance from the source at which we extract the waveform data and provide a conservative estimate of the mismatch accuracy. We find that the upper limit on the mismatch uncertainty of our waveforms (including multipoles ℓ≤5) is 0.4%. In doing this we present a consistent approach to combining mismatch uncertainties from multiple error sources. We compare this release to previous catalogs and discuss how these new simulations complement the existing public datasets. In particular, this is the first catalog to uniformly cover this parameter space of single-spin binaries and there was previously only sparse coverage of the precessing-binary parameter space for mass ratios ≳5. We discuss applications of these new data, and the most urgent directions for future simulation work.

Published by the American Physical Society
2024