bluuebunny/crossref_metadata_2025 huggingface dataset:
How to build a lichen: from metabolite release to symbiotic interplay
Authors: Pichler Gregor , Muggia Lucia , Carniel Fabio Candotto , Grube Martin , Kranner Ilse
Published: January 2023

Exposing their vegetative bodies to the light, lichens are outstanding amongst other fungal symbioses. Not requiring a pre‐established host, ‘lichenized fungi’ build an entirely new structure together with microbial photosynthetic partners that neither can form alone. The signals involved in the transition of a fungus and a compatible photosynthetic partner from a free‐living to a symbiotic state culminating in thallus formation, termed ‘lichenization’, and in the maintenance of the symbiosis, are poorly understood. Here, we synthesise the puzzle pieces of the scarce knowledge available into an updated concept of signalling involved in lichenization, comprising five main stages: (1) the ‘pre‐contact stage’, (2) the ‘contact stage’, (3) ‘envelopment’ of algal cells by the fungus, (4) their ‘incorporation’ into a pre‐thallus and (5) ‘differentiation’ into a complex thallus. Considering the involvement of extracellularly released metabolites in each phase, we propose that compounds such as fungal lectins and algal cyclic peptides elicit early contact between the symbionts‐to‐be, whereas phytohormone signalling, antioxidant protection and carbon exchange through sugars and sugar alcohols are of continued importance throughout all stages. In the fully formed lichen thallus, secondary lichen metabolites and mineral nutrition are suggested to stabilize the functionalities of the thallus, including the associated microbiota.
Effects of virtual tour on perioperative pediatric anxiety
Authors: Franco Castanys Teresa , Jiménez Carrión Anabel , Ródenas Gómez Frederic , Clemente García Sandra , Melero Mascaray Alícia , Janeiro Amela Marisa , Busquets Bonet Jordi
Published: January 2023

Background

There is a high incidence of perioperative anxiety in the pediatric population, with adverse side effects, such as emergency delirium and maladaptive postoperative behaviors.

Aims

The study's objective was to compare the level of preoperative anxiety in children after standard preparation plus a virtual tour of the operating room vs. standard preparation alone.

Patients/Methods

This was a prospective single‐center, randomized, controlled, blinded trial with parallel assignment, registered as NCT04043663. Eligible subjects were healthy children (ASA I‐II) aged 4–12, scheduled for outpatient surgery. Five visits were conducted during the study, two at the hospital and three over the phone. Variables assessed were child's anxiety through the modified Yale Perioperative Anxiety Scale, demographic data, cooperation with induction through the Induction Compliance Checklist, preoperative parental anxiety through the State–Trait Anxiety Inventory and Anxiety Visual Analog Scale, the postoperative delirium degree through the Pediatric Anesthesia Emergence Delirium Scale, the presence of behavioral changes through the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery, and the overall parental satisfaction.

Results

A total of 125 participants were included; 61 (48.8%) of them were randomized to the Virtual Tour Group (VT+) and 64 (51.2%) to the Non‐virtual Tour Group (VT‐). Yale Preoperative Anxiety Scale results in VT+ vs. VT‐ were mean 27.26 vs. 32.57, and median 23.4 (CI 95% 23.4–23.4) vs. 23.4 (CI 95% 23.4–33.4), (p = .0086). In the VT+ group, satisfaction was higher for questions one (p = .0213), three (p = <.0001), and four (p = .0130). Throughout the study, we observed a significant reduction in perioperative anxiety in the VT+ group, facilitating anesthetic induction in perfect (p = .018) and moderate compliance (p = .0428). The other variables did not show statistically significant differences.

Conclusion

Our study confirms previous studies that found virtual tours for perioperative patients may reduce perioperative anxiety and improve satisfaction. We found no impact on longer‐term outcomes.
Chromosome‐level wild Hevea brasiliensis genome provides new tools for genomic‐assisted breeding and valuable loci to elevate rubber yield
Authors: Cheng Han , Song Xiaoming , Hu Yanshi , Wu Tingkai , Yang Qihang , An Zewei , Feng Shuyan , Deng Zhi , Wu Wenguan , Zeng Xia , Tu Min , Wang Xiyin , Huang Huasun
Published: January 2023

The rubber tree (Hevea brasiliensis) is grown in tropical regions and is the major source of natural rubber. Using traditional breeding approaches, the latex yield has increased by sixfold in the last century. However, the underlying genetic basis of rubber yield improvement is largely unknown. Here, we present a high‐quality, chromosome‐level genome sequence of the wild rubber tree, the first report on selection signatures and a genome‐wide association study (GWAS) of its yield traits. Population genomic analysis revealed a moderate population divergence between the Wickham clones and wild accessions. Interestingly, it is suggestive that H. brasiliensis and six relatives of the Hevea genus might belong to the same species. The selective sweep analysis found 361 obvious signatures in the domesticated clones associated with 245 genes. In a 15‐year field trial, GWAS identified 155 marker–trait associations with latex yield, in which 326 candidate genes were found. Notably, six genes related to sugar transport and metabolism, and four genes related to ethylene biosynthesis and signalling are associated with latex yield. The homozygote frequencies of the causal nonsynonymous SNPs have been greatly increased under selection, which may have contributed to the fast latex yield improvement during the short domestication history. Our study provides insights into the genetic basis of the latex yield trait and has implications for genomic‐assisted breeding by offering valuable resources in this new domesticated crop.
Two for two: Dual therapy with erlotinib and acitretin for twins with severe keratoderma in Olmsted syndrome
Authors: Butala Sneha , Phan Sheshanna , Siegel Dawn H. , Carlberg Valerie , Paller Amy S.
Published: January 2023

Olmsted syndrome (OS) is a rare genetic disorder, characterized by painful palmoplantar keratoderma (PPK), periorificial and intertriginous hyperkeratoses, and alopecia. Fewer than 75 cases have been described. Variants in TRPV3 result in constitutive activation of transient receptor potential vanilloid 3, leading to increased epidermal growth factor receptor (EGFR) signaling, palmoplantar epidermal hyperproliferation, and exquisite lesional pain. We describe pre‐school aged twins with OS with partial improvement from oral erlotinib, an EGFR inhibitor, but dramatic reduction of their persistent palmoplantar thickening and pain from adding acitretin.
Neural deficits in anticipatory and consummatory reward processing are uniquely associated with current depressive symptoms during adolescence
Authors: Thompson Brittney , Santopetro Nicholas J. , Brush Christopher J. , Foti Dan , Hajcak Greg
Published: January 2023

Deficits within the consummatory phase of reward processing are associated with increased depression symptoms and risk; however, few studies have also examined other aspects of reward processing in relation to depression. In the current study, a community sample of 121 adolescents (Mage = 13.1, Min = 11.14; Max = 15.12; 54% male) completed self‐report questionnaires to assess depressive symptoms and the monetary incentive delay (MID) task while EEG was recorded. Results indicated that a reduced cue‐P300 as well as a reduced reward positivity (RewP) and feedback negativity (FN) to gain and loss feedback, respectively, were associated with increased depressive symptoms; on the other hand, SPN and feedback P300 were unrelated to depressive symptoms. An exploratory multiple regression analysis revealed that a reduced money cue‐P300, a reduced RewP, and a reduced (i.e., less negative) FN, all explained unique variance in depressive symptoms. The current study demonstrates that reduced cue‐P300, RewP, and FN amplitudes may reflect distinct deficits in reward processing among adolescents with increased depressive symptoms. Notably, this study is one of the first to leverage the MID task in adolescents in relation to depressive symptoms, allowing for a more in‐depth view of the individual differences in reward processing among adolescents with increased depressive symptomatology.
Effects of respiratory phases on the processing of emotional and non‐emotional visual stimuli
Authors: Mizuhara Keita , Nittono Hiroshi
Published: January 2023

The number of studies investigating the relationship between respiratory phases and cognitive/neural processing of external events has been increasing, but the findings remain controversial. This registered report examined the effect of the respiratory phase on the discrimination accuracy of visual stimuli in the emotional and non‐emotional domains. Forty‐two healthy young participants were asked to choose fearful over neutral facial expressions and to choose high‐contrast over low‐contrast Gabor patches during spontaneous nasal respiration. Event‐related potentials (ERPs) were also recorded for each type of stimulus presented during each respiratory phase. It was hypothesized that discrimination accuracy would be higher when the stimuli were presented during inhalation than during exhalation. It was also hypothesized that the amplitudes of ERPs elicited by the stimuli would be greater during inhalation than during exhalation. For comparison, the effect of the cardiac phase was examined, with the expectation that discrimination accuracy would be higher when the stimuli were presented during systole than during diastole. It was also hypothesized that the amplitudes of ERPs elicited by the stimuli would be greater during systole than during diastole. As expected, the results indicated that fear discrimination accuracy was higher during inhalation than exhalation and during systole than diastole. However, this was not the case for contrast discrimination. No differences in ERPs were observed between respiratory phases in either task. These results suggest that natural breathing in through the nose facilitates the discrimination of emotional stimuli, possibly via subcortical processes.
Parental affect profiles predict child emotion regulation and classroom adjustment in families experiencing homelessness
Authors: Labella Madelyn H. , Distefano Rebecca , Merrick Jillian S. , Ramakrishnan Jyothi L. , Thibodeau Eric L. , Masten Ann S.
Published: January 2023

Parenting shapes the development of emotion regulation skills in early childhood, laying a key foundation for social‐emotional adjustment. Unfortunately, high adversity exposure may disrupt parental emotion socialization practices and children's regulatory development. The current study used variable‐ and person‐centered approaches to evaluate links among parental emotion expressiveness, children's observed emotion regulation, and teacher‐reported adjustment among 214 4‐ to 6‐year‐old children experiencing homelessness, an indicator of high cumulative risk and acute adversity. Structured parent‐child interaction tasks were recorded on site in emergency shelters over the summer and micro‐socially coded for parent and child expressions of anger, positive affect, and internalizing distress. We anticipated that parental modeling of predominantly negative emotion expression would be associated with more child dysregulation during parent‐child interaction and worse adjustment at school, as reported by teachers the following school year. Preliminary analyses indicated that children's observed difficulty downregulating anger was associated robustly with teacher‐reported social‐behavioral problems. Latent profile analysis was used to identify three patterns of parental emotion expression characterized by above‐average expression of positive affect, internalizing distress, and anger. Parents’ likelihood of membership in the elevated anger profile significantly predicted children's observed difficulty down‐regulating anger and higher social‐behavioral problems at school. In addition to ongoing efforts to reduce poverty‐related risk, supporting adaptive anger regulation in parents and young children may be important for enhancing resilience among families experiencing homelessness and similar conditions of high cumulative risk.
Progression of human monkeypox infection despite tecovirimat in an immunocompromised adult
Authors: Dammann Fabian , Raja Mohammed , Camargo Jose F.
Published: January 2023

We report a case of an immunocompromised man with monkeypox who experienced disease progression despite timely initiation of tecovirimat and ultimately required utilization of cidofovir and VIGIV for treatment. In immunocompromised patients, monkeypox might present with a more severe course of disease requiring consideration of alternative treatment strategies
PHYTOCHROME‐INTERACTING FACTORS are involved in starch degradation adjustment via inhibition of the carbon metabolic regulator QUA‐QUINE STARCH in Arabidopsis
Authors: Lee Sang Woo , Choi Dasom , Moon Heewon , Kim Sujeong , Kang Hajeong , Paik Inyup , Huq Enamul , Kim Dong‐Hwan
Published: January 2023

As sessile organisms, plants encounter dynamic and challenging environments daily, including abiotic/biotic stresses. The regulation of carbon and nitrogen allocations for the synthesis of plant proteins, carbohydrates, and lipids is fundamental for plant growth and adaption to its surroundings. Light, one of the essential environmental signals, exerts a substantial impact on plant metabolism and resource partitioning (i.e., starch). However, it is not fully understood how light signaling affects carbohydrate production and allocation in plant growth and development. An orphan gene unique to Arabidopsis thaliana, named QUA‐QUINE STARCH (QQS) is involved in the metabolic processes for partitioning of carbon and nitrogen among proteins and carbohydrates, thus influencing leaf, seed composition, and plant defense in Arabidopsis. In this study, we show that PHYTOCHROME‐INTERACTING bHLH TRANSCRIPTION FACTORS (PIFs), including PIF4, are required to suppress QQS during the period at dawn, thus preventing overconsumption of starch reserves. QQS expression is significantly de‐repressed in pif4 and pifQ, while repressed by overexpression of PIF4, suggesting that PIF4 and its close homologs (PIF1, PIF3, and PIF5) act as negative regulators of QQS expression. In addition, we show that the evening complex, including ELF3 is required for active expression of QQS, thus playing a positive role in starch catabolism during night‐time. Furthermore, QQS is epigenetically suppressed by DNA methylation machinery, whereas histone H3 K4 methyltransferases (e.g., ATX1, ATX2, and ATXR7) and H3 acetyltransferases (e.g., HAC1 and HAC5) are involved in the expression of QQS. This study demonstrates that PIF light signaling factors help plants utilize optimal amounts of starch during the night and prevent overconsumption of starch before its biosynthesis during the upcoming day.
Natural variations in the PbCPK28 promoter regulate sugar content through interaction with PbTST4 and PbVHA‐A1 in pear
Authors: Li Jiaming , Zhu Rongxiang , Zhang Mingyue , Cao Beibei , Li Xiaolong , Song Bobo , Liu Zhongchi , Wu Jun
Published: January 2023

Soluble sugars play an important role in plant growth, development and fruit quality. Pear fruits have demonstrated a considerable improvement in sugar quality during their long history of selection. However, little is known about the underlying molecular mechanisms accompanying the changes in fruit sugar content as a result of selection by horticulturists. Here, we identified a calcium‐dependent protein kinase (PbCPK28), which is located on LG15 and is present within a selective sweep region, thus linked to the quantitative trait loci for soluble solids. Association analysis indicates that a single nucleotide polymorphism‐13 variation (SNP13T/C) in the PbCPK28 regulatory region led to fructose content diversity in pear. Elevated expression of PbCPK28 resulted in significantly increased fructose levels in pear fruits. Furthermore, PbCPK28 interacts with and phosphorylates PbTST4, a proton antiporter, thereby coupling the sugar import into the vacuole with proton export. We demonstrated that residues S277 and S314 of PbTST4 are crucial for its function. Additionally, PbCPK28 interacts with and phosphorylates the vacuolar hydrogen proton pump PbVHA‐A1, which could provide proton motive forces for PbTST4. We also found that the T11 and Y120 phosphorylation sites in PbVHA‐A1 are essential for its function. Evolution analysis and yeast‐two‐hybrid results support that the CPK‐TST/CPK‐VHA‐A regulatory network is highly conserved in plants, especially the corresponding phosphorylation sites. Together, our work identifies an agriculturally important natural variation and an important regulatory network, allowing genetic improvement of fruit sugar contents in pears through modulation of PbCPK28 expression and phosphorylation of PbTST4 and PbVHA‐A1.
Partial validation of the Vcheck canine pancreatic lipase assay
Authors: Jakus Paulina , Strage Emma , Abrahamsson Johanna , Hillström Anna
Published: January 2023

Measurement of canine pancreatic lipase immunoreactivity (cPLI) is used for diagnosing pancreatitis in dogs. Because pancreatitis can be a life‐threatening disease with severe complications, an in‐house cPLI test would be valuable to obtain rapid test results. The aim of this study was to evaluate a point‐of‐care cPLI test, Vcheck cPL. Precision, determined according to EP15, and linearity under dilution were determined and judged against preset quality goals. Results from the Vcheck cPL were compared with a previously validated cPLI ELISA, Spec cPL. In a retrospective study, cPLI results from dogs with and without acute pancreatitis, as determined by pancreatic ultrasound examination, were investigated to assess the performance of the assay in a clinical setting. Statistical analysis included the Mann–Whitney test, Chi‐square test, and Passing–Bablok regression analysis with a significance level of 0.05. Precision of the assay was acceptable, with intra‐, inter‐, and total coefficients of variation (CV%) less than 12.1%, 6.4%, and 12.1%, respectively. Results from the linearity study indicated that the method was acceptably linear at lower concentrations but not in the high‐concentration range. The method comparison study revealed that Vcheck generally measured higher concentrations compared with Spec cPL, and that the methods should not be used interchangeably. Dogs with acute pancreatitis had significantly higher cPLI concentrations compared with dogs without pancreatitis (P < 0.01), but there was a marked overlap in cPL concentrations between the two groups.
Lipin1 plays complementary roles in myofibre stability and regeneration in dystrophic muscles
Authors: Jama Abdulrahman , Alshudukhi Abdullah A. , Burke Steve , Dong Lixin , Kamau John Karanja , Voss Andrew Alvin , Ren Hongmei
Published: January 2023

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by dystrophin mutations, leading to the loss of sarcolemmal integrity, and resulting in progressive myofibre necrosis and impaired muscle function. Our previous studies suggest that lipin1 is important for skeletal muscle regeneration and myofibre integrity. Additionally, we discovered that mRNA expression levels of lipin1 were significantly reduced in skeletal muscle of DMD patients and the mdx mouse model. To understand the role of lipin1 in dystrophic muscle, we generated dystrophin/lipin1 double knockout (DKO) mice, and compared the limb muscle pathology and function of wild‐type B10, muscle‐specific lipin1 deficient (lipin1Myf5cKO), mdx and DKO mice. We found that further knockout of lipin1 in dystrophic muscle exhibited a more severe phenotype characterized by increased necroptosis, fibrosis and exacerbated membrane damage in DKO compared to mdx mice. In barium chloride‐induced muscle injury, both lipin1Myf5cKO and DKO showed prolonged regeneration at day 14 post‐injection, suggesting that lipin1 is critical for muscle regeneration. In situ contractile function assays showed that lipin1 deficiency in dystrophic muscle led to reduced specific force production. Using a cell culture system, we found that lipin1 deficiency led to elevated expression levels of necroptotic markers and medium creatine kinase, which could be a result of sarcolemmal damage. Most importantly, restoration of lipin1 inhibited the elevation of necroptotic markers in differentiated primary lipin1‐deficient myoblasts. Overall, our data suggests that lipin1 plays complementary roles in myofibre stability and muscle function in dystrophic muscles, and overexpression of lipin1 may serve as a potential therapeutic strategy for dystrophic muscles.

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Key points

We identified that lipin1 mRNA expression levels are significantly reduced in skeletal muscles of Duchenne muscular dystrophy patients and mdx mice.

We found that further depletion of lipin1 in skeletal muscles of mdx mice induces more severe dystrophic phenotypes, including enhanced myofibre sarcolemma damage, muscle necroptosis, inflammation, fibrosis and reduced specific force production.

Lipin1 deficiency leads to elevated expression levels of necroptotic markers, whereas restoration of lipin1 inhibits their expression.

Our results suggest that lipin1 is functionally complementary to dystrophin in muscle membrane integrity and muscle regeneration.
Analyzing Extreme Sea State Conditions by Time-Series Simulation Accounting for Seasonality
Authors: Vanem Erik
Published: January 2023

This article presents an extreme value analysis on data of significant wave height based on time-series simulation. A method to simulate time series with given marginal distribution and preserving the autocorrelation structure in the data is applied to significant wave height data. Then, extreme value analysis is performed by simulating from the fitted time-series model that preserves both the marginal probability distribution and the autocorrelation. In this way, the effect of serial correlation on the extreme values can be taken into account, without subsampling and de-clustering of the data. The effect of serial correlation on estimating extreme wave conditions have previously been highlighted, and failure to account for this effect will typically lead to an overestimation of extreme conditions. This is demonstrated by this study, which compares extreme value estimates from the simulated times-series model with estimates obtained directly from the marginal distribution assuming that 3-h significant wave heights are independent and identically distributed. A dataset of significant wave height provided as part of a second benchmark exercise on environmental extremes that was presented at OMAE 2021 has been analyzed. This article is an extension of a study presented at OMAE 2022 (OMAE2022-78795) and includes additional preprocessing of the data to account for seasonality and new results.
Transient behavior of a salinity gradient solar pond under Mediterranean climate
Authors: Rghif Yassmine , Sayer Asaad , B. Mahood Hameed
Published: January 2023

This paper aims to investigate the transient behavior of a salinity gradient solar pond(SGSP) under Mediterranean climate. For this propose, a 2D numerical model is developed in which the absorption of solar radiation by different layers of saline water, the wind effect at free surface, the heat losses and the development of the double-diffusive convection in the lower and upper convective zones are considered. The governing equations of continuity, momentum, thermal energy and diffusion are solved using the finite volume method with SIMPLE algorithm. The validity of the numerical model developed in Fortran95 is achieved through the comparisons of the results computed with the available numerical and experimental results obtained by literature studies. Results show that the developed numerical model can predict transient behavior of the SGSPs with a good accuracy. As an application of this model, temperature, salt concentration, energy stored and storage efficiency variations of a proposed SGSP are analyzed under Mediterranean climate. The results show that the lower convective zone(LCZ) temperature increases from 15 °C to around 95 °C whereas the temperature of the upper convective zone(UCZ) varies sinusoidally depending on that of the ambient air. Furthermore, the salt concentration of the LCZ decreases from 250kg/m3 to around 248kg/m3 while that of the UCZ increases from50 kg/m3 to about 52kg/m3. Additionally, the thermal energy stored is around 135MJ with an efficiency of about 38% which confirms the capacity of the SGSP to store thermal energy as sensible heat.
Performance Evaluation of an Evacuated Flat-Plate Collector System for Domestic Hot Water Applications
Authors: Saeed Hamza , Mahmood Mariam , Nazir Hassan , Waqas Adeel , Ahmad Naveed , Ali Majid , Haseeb Abdul , Sajid Muhammad Bilal
Published: January 2023

Rapid population growth and increasing energy demand in developing countries are the key drivers behind rising concerns such as energy poverty and environmental degradation. Harnessing solar energy can help the developing countries inch closer to sustainable economic growth. This article presents the performance analysis of a solar water heating system based on an evacuated flat-plate collector (EFPC). EFPCs offer higher optical performance and lower thermal losses in comparison with conventional solar collectors. In this study, a multiparametric analysis provides the guidelines for the design and optimization of a novel low vacuum EFPC system under ambient conditions, for domestic hot water (DHW) applications. A small-scale solar thermal collector system based on a low vacuum (17.5–20 kPa) EFPC of a total area of 4.0 m2 is designed and installed. The system is coupled with a storage tank composed of the helical copper coil configuration inside the tank, which is used as a heat exchanger from a primary loop to a secondary loop. A series of real-time experiments are performed under ambient conditions from December to April. The thermal efficiency of the EFPCs reaches a maximum value of 73.2%, with the glycol–water mixture as a heat transfer fluid at an inlet temperature of 31.2 °C, when the ambient temperature is 15.3 °C, average irradiance is 679.2 Wm−2, and vacuum pressure is 20 kPa. For this duration, the exergy efficiency reaches a peak value of 16%. This EFPC system provides 100 liters of hot water at 57–69 °C per day for DHW consumption when the average ambient temperature is 24 °C. The overall results highlight the potential of EFPCs for hot water applications. Furthermore, an efficiently optimized EFPC system can also be used for space heating during the winter season.
Meteorites have inherited nucleosynthetic anomalies of potassium-40 produced in supernovae
Authors: Nie Nicole X. , Wang Da , Torrano Zachary A. , Carlson Richard W. , O’D. Alexander Conel M. , Shahar Anat
Published: January 2023

Meteorites record processes that occurred before and during the formation of the Solar System in the form of nucleosynthetic anomalies: isotopic compositions that differ from the Solar System patterns. Nucleosynthetic anomalies are rarely seen in volatile elements such as potassium at bulk meteorite scale. We measured potassium isotope ratios in 32 meteorites and identified nucleosynthetic anomalies in the isotope potassium-40. The anomalies are larger and more variable in carbonaceous chondrite (CC) meteorites than in noncarbonaceous (NC) meteorites, indicating that CCs inherited more material produced in supernova nucleosynthesis. The potassium-40 anomaly of Earth is close to that of the NCs, implying that Earth’s potassium was mostly delivered by NCs.
Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides
Authors: Bridges Hannah R. , Blaza James N. , Yin Zhan , Chung Injae , Pollak Michael N. , Hirst Judy
Published: January 2023

The molecular mode of action of biguanides, including the drug metformin, which is widely used in the treatment of diabetes, is incompletely characterized. Here, we define the inhibitory drug-target interaction(s) of a model biguanide with mammalian respiratory complex I by combining cryo–electron microscopy and enzyme kinetics. We interpret these data to explain the selectivity of biguanide binding to different enzyme states. The primary inhibitory site is in an amphipathic region of the quinone-binding channel, and an additional binding site is in a pocket on the intermembrane-space side of the enzyme. An independent local chaotropic interaction, not previously described for any drug, displaces a portion of a key helix in the membrane domain. Our data provide a structural basis for biguanide action and enable the rational design of medicinal biguanides.
Infection infidelities drive innate immunity
Authors: Kagan Jonathan C.
Published: January 2023

Unsuccessful pathogenic activities may be key to activating host defenses to infection
Decoding complex order in reticular frameworks
Authors: Yaghi Omar M. , Rong Zichao
Published: January 2023

Periodicity and aperiodicity coexist in a nonchaotic, information-rich crystal structure
Anti-σ
28
Factor FlgM Regulates Flagellin Gene Expression and Flagellar Polarity of Treponema denticola
Authors: Kurniyati Kurni , Chang Yunjie , Guo Wangbiao , Liu Jun , Malkowski Michael G. , Li Chunhao
Published: January 2023

Spirochetes are a group of bacteria that cause several human diseases. A unique aspect of spirochetes is that they have bipolar periplasmic flagella (PFs), which bestow on the spirochetes a unique spiral shape and distinct swimming behaviors.
Complete Genome Sequences of Extraintestinal Pathogenic Escherichia coli Clinical Isolates from Danish Ulcerative Colitis Patients
Authors: Meski Simon , Struve Carsten , Mirsepasi-Lauridsen Hengameh C. , Petersen Andreas M. , Jelsbak Lotte , Skovgaard Ole , Krogfelt Karen A.
Published: January 2023

Extraintestinal pathogenic
Escherichia coli
(ExPEC) is a potential factor in ulcerative colitis etiology. We report here the complete genome and plasmid sequences of three
Escherichia coli
isolates, C 237-04 (p7), C 236-04A (p10A), and C 691-04A (p19A), obtained from fecal samples from ulcerative colitis patients in Copenhagen, Denmark.
Efficacy in Galleria mellonella Larvae and Application Potential Assessment of a New Bacteriophage BUCT700 Extensively Lyse Stenotrophomonas maltophilia
Authors: Li Yahao , Pu Mingfang , Han Pengjun , Li Mengzhe , An Xiaoping , Song Lihua , Fan Huahao , Chen Zeliang , Tong Yigang
Published: January 2023

The risk of
Stenotrophomonas maltophilia
infections mediated by the medical devices is exacerbated with an increase in the number of ICU patients during the Corona Virus Disease 2019 (COVID-19) epidemic. Complications caused by
S. maltophilia
infections could complicate the state of an illness, greatly extending the length of hospitalization and increasing the financial burden.
Burosumab in management of X-linked hypophosphataemia: a retrospective cohort study of growth and serum phosphate levels
Authors: Walker Emma Yi Xiu , Lindsay Timothy Alexander James , Allgrove Jeremy , Marlais Matko , Bockenhauer Detlef , Hayes Wesley
Published: January 2023

Background

Burosumab, an antifibroblast growth factor 23 monoclonal antibody, improves rickets severity, symptoms and growth in children with X-linked hypophosphataemia (XLH) followed up to 64 weeks in clinical trials. International dosing guidance recommends targeting normal serum phosphate concentration; however, some children may not achieve this despite maximal dosing. This study compares clinical outcomes in children with XLH on long-term burosumab treatment who achieved normal phosphate versus those who did not.

Methods

Single-centre retrospective review of a large paediatric cohort with XLH treated with burosumab. We evaluated growth and biochemical markers of bone health in those who did compared with those who did not achieve normal plasma phosphate concentration.

Results

Fifty-five children with XLH with median age of 11.7 (IQR 6.8–15.5) years were included. 27 (49%) had low plasma phosphate concentration, and 27 (49%) had normal phosphate after a median burosumab treatment duration of 3.3 (IQR 2.6–3.7) years. 1 (2%) did not have a recent phosphate level recorded. No difference in growth was found between normal and abnormal phosphate groups (p=0.9).

Conclusions

Young children with XLH experience sustained growth on long-term burosumab treatment, although without normal plasma phosphate concentration in many. Consideration should be made to changing burosumab dosing recommendations to target normalisation of alkaline phosphatase, as opposed to plasma phosphate concentration.
Ophthalmological outcome of 6.5 years children treated for retinopathy of prematurity: a Swedish register study
Authors: Larsson Eva , Hellström Ann , Tornqvist Kristina , Wallin Agneta , Sunnqvist Birgitta , Sandgren Hochhard Karin , Lundgren Pia , Al-Hawasi Abbas , Teär Fahnehjelm Kristina , Gränse Lotta , Holmstrom Gerd
Published: January 2023

Aims

To determine the ophthalmological outcome at 6.5 years of age in children treated for retinopathy of prematurity (ROP), and registered in the national Swedish National Register for ROP register.

Methods

Data on ROP, treatment and ophthalmological outcome were retrieved from the register. Visual acuity (VA), refractive errors and strabismus, together with visual impairment (VI) and any significant eye problem, defined as VA >0.5 logarithm of the minimal angle of resolution (logMAR) and/or strabismus and/or any refractive error were analysed. Risk factors such as sex, gestational age (GA), birth weight SD score, number of treatments and retreatments, postnatal age and postmenstrual age at first treatment were analysed.

Results

Follow-up data were available in 232 of 270 children born between 2007 and 2014 who had been treated for ROP. VI (VA >0.5 logMAR) was found in 32 (14%), strabismus in 82 (38%), refractive errors in 114 (52%) and significant eye problem in 143 (65%) children. Retreatment was a risk factor for VI and refractive errors. Male sex and neonatal brain lesion were risk factors for strabismus. An additional week of GA at birth reduced the risk for refractive errors, strabismus and significant eye problems.

Conclusion

The results of the present study revealed a high number of eye problems in children treated for ROP, emphasising the need for long-term follow-up. Retreatment of ROP was a risk factor for VI, and emphasises the importance of an accurate first treatment for the long-term ophthalmological outcome.
Effectiveness of a judo-specific injury prevention programme: a randomised controlled trial in recreational judo athletes
Authors: von Gerhardt Amber L , Reurink Guus , Kerkhoffs Gino M M J , Verhagen Evert , Krabben Kai , Mooren Jeroen , Gal Jessica S I , Brons Arnold , Joorse Ronald , van den Broek Benny , Kemler Ellen , Tol Johannes L
Published: January 2023

Objectives

To evaluate the effectiveness of a trainer-supervised judo-specific injury prevention warm-up programme on overall injury prevalence.

Methods

We conducted a two-arm, cluster randomised controlled trial; the Injury Prevention and Performance Optimization Netherlands (IPPON) study. Judo athletes aged≥12 years were randomised by judo school to IPPON intervention or control group who performed their usual warm-up. Primary outcome was overall injury prevalence (%) over the follow-up period (16–26 weeks) measured fortnightly with the Oslo Sports and Trauma Research Centre Questionnaire. A modified intention-to-treat analysis was performed due to COVID-19, with estimates for the primary outcome obtained using generalised linear mixed models. Secondary outcomes included: prevalence of severe injuries, overall incidence, time-loss injuries, exposure, adherence and experiences of trainers and athletes.

Results

269 judo athletes (IPPON: 117, Control: 152) were included. Mean injury prevalence over 16–26 weeks was 23% (95% CI 20% to 26%) in the IPPON and 28% (95% CI 25% to 30%) in the control group. We observed no significant difference of all reported injuries (OR 0.72 in favour of the IPPON group; 95% CI 0.37 to 1.39). Secondary outcomes also demonstrated no significant differences between groups. Specifically, no significant difference of severe injuries was reported (OR 0.80 in favour of the IPPON group; 95% CI 0.36 to 1.78). All trainers and 70% of athletes perceived the IPPON intervention as successful.

Conclusion

The IPPON intervention did not significantly reduce the overall and severe injury prevalence. Despite this, we suggest the IPPON intervention be considered as an useful alternative to regular judo warm-up, given the high adherence and the positive clinical experiences of trainers and athletes.

Trial registration number

NTR7698.
Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study
Authors: Jia Jianping , Zhao Tan , Liu Zhaojun , Liang Yumei , Li Fangyu , Li Yan , Liu Wenying , Li Fang , Shi Shengliang , Zhou Chunkui , Yang Heyun , Liao Zhengluan , Li Yang , Zhao Huiying , Zhang Jintao , Zhang Kunnan , Kan Minchen , Yang Shanshan , Li Hao , Liu Zhongling , Ma Rong , Lv Jihui , Wang Yue , Yan Xin , Liang Furu , Yuan Xiaoling , Zhang Jinbiao , Gauthier Serge , Cummings Jeffrey
Published: January 2023

Objective

To identify an optimal lifestyle profile to protect against memory loss in older individuals.

Design

Population based, prospective cohort study.

Setting

Participants from areas representative of the north, south, and west of China.

Participants

Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009.

Main outcome measures

Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample.

Results

29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52).

Conclusion

A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline.

Trial registration

ClinicalTrials.gov
NCT03653156
.
Phenotypic CD8 T cell profiling in chronic hepatitis B to predict HBV-specific CD8 T cell susceptibility to functional restoration in vitro
Authors: Rossi Marzia , Vecchi Andrea , Tiezzi Camilla , Barili Valeria , Fisicaro Paola , Penna Amalia , Montali Ilaria , Daffis Stephane , Fletcher Simon P , Gaggar Anuj , Medley Jonathan , Graupe Michael , Lad Latesh , Loglio Alessandro , Soffredini Roberta , Borghi Marta , Pollicino Teresa , Musolino Cristina , Alfieri Arianna , Brillo Federica , Laccabue Diletta , Massari Marco , Boarini Chiara , Abbati Gianluca , Pedrazzi Giuseppe , Missale Gabriele , Lampertico Pietro , Ferrari Carlo , Boni Carolina
Published: January 2023

Objective

Exhausted hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection are broadly heterogeneous. Characterisation of their functional impairment may allow to distinguish patients with different capacity to control infection and reconstitute antiviral function.

Design

HBV dextramer+CD8 T cells were analysed ex vivo for coexpression of checkpoint/differentiation markers, transcription factors and cytokines in 35 patients with HLA-A2+chronic hepatitis B (CHB) and in 29 control HBsAg negative CHB patients who seroconverted after NUC treatment or spontaneously. Cytokine production was also evaluated in HBV peptide-stimulated T cell cultures, in the presence or absence of antioxidant, polyphenolic, PD-1/PD-L1 inhibitor and TLR-8 agonist compounds and the effect on HBV-specific responses was further validated on additional 24 HLA-A2 negative CHB patients.

Results

Severely exhausted HBV-specific CD8 T cell subsets with high expression of inhibitory receptors, such as PD-1, TOX and CD39, were detected only in a subgroup of chronic viraemic patients. Conversely, a large predominance of functionally more efficient HBV-specific CD8 T cell subsets with lower expression of coinhibitory molecules and better response to in vitro immune modulation, typically detected after resolution of infection, was also observed in a proportion of chronic viraemic HBV patients. Importantly, the same subset of patients who responded more efficiently to in vitro immune modulation identified by HBV-specific CD8 T cell analysis were also identified by staining total CD8 T cells with PD-1, TOX, CD127 and Bcl-2.

Conclusions

The possibility to distinguish patient cohorts with different capacity to respond to immune modulatory compounds in vitro by a simple analysis of the phenotypic CD8 T cell exhaustion profile deserves evaluation of its clinical applicability.
Targeting m6A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer
Authors: Bao Yi , Zhai Jianning , Chen Huarong , Wong Chi Chun , Liang Cong , Ding Yanqiang , Huang Dan , Gou Hongyan , Chen Danyu , Pan Yasi , Kang Wei , To Ka Fai , Yu Jun
Published: January 2023

Objective

The role of N6-methyladenosine (m6A) in tumour immune microenvironment (TIME) remains understudied. Here, we elucidate function and mechanism of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in colorectal cancer (CRC) TIME.

Design

Clinical significance of YTHDF1 was assessed in tissue microarrays (N=408) and TCGA (N=526) cohorts.YTHDF1function was determined in syngeneic tumours, intestine-specificYthdf1knockin mice, and humanised mice. Single-cell RNA-seq (scRNA-seq) was employed to profile TIME. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA sequencing (RNA-seq) and ribosome sequencing (Ribo-seq) were used to identify YTHDF1 direct targets. Vesicle-like nanoparticles (VNPs)-encapsulatedYTHDF1-siRNA was used forYTHDF1silencing in vivo.

Results

YTHDF1expression negatively correlated with interferon-γ gene signature in TCGA-CRC. Concordantly, YTHDF1 protein negatively correlated with CD8+T-cell infiltration in independent tissue microarrays cohorts, implying its role in TIME. Genetic depletion ofYthdf1augmented antitumour immunity in CT26 (MSS-CRC) and MC38 (MSI-H-CRC) syngeneic tumours, whileYthdf1knockin promoted an immunosuppressive TIME facilitating CRC in azoxymethane-dextran sulphate-sodium orApcMin/+models. scRNA-seq identified reduction of myeloid-derived suppressor cells (MDSCs), concomitant with increased cytotoxic T cells inYthdf1knockout tumours. Integrated MeRIP-seq, RNA-seq and Ribo-seq revealed p65/Rela as a YTHDF1 target. YTHDF1 promoted p65 translation to upregulate CXCL1, which increased MDSC migration via CXCL1-CXCR2 axis. Increased MSDCs in turn antagonised functional CD8+T cells in TIME. Importantly, targeting YTHDF1 by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) or VNPs-siYTHDF1boosted anti-PD1 efficacy in MSI-H CRC, and overcame anti-PD1 resistance in MSS CRC.

Conclusion

YTHDF1 impairs antitumour immunity via an m6A-p65-CXCL1/CXCR2 axis to promote CRC and serves as a therapeutic target in immune checkpoint blockade therapy.
Proton pump inhibitors and the risk of inflammatory bowel disease: population-based cohort study
Authors: Abrahami Devin , Pradhan Richeek , Yin Hui , Yanofsky Russell , McDonald Emily Gibson , Bitton Alain , Azoulay Laurent
Published: January 2023

Objective

To determine whether the use of proton pump inhibitors (PPIs) compared with the use of histamine-2 receptor antagonists (H2RAs) is associated with an increased risk of inflammatory bowel disease (IBD).

Design

Population-based cohort study designed to address the impact of protopathic bias.

Setting

General practices contributing data to the UK Clinical Practice Research Datalink GOLD.

Participants

1 498 416 initiators of PPIs and 322 474 initiators of H2RAs from 1 January 1990 to 31 December 2018, with follow-up until 31 December 2019. Patients were analysed according to the timing of the IBD diagnosis after treatment initiation (early vs late).

Main outcome measures

Standardised morbidity ratio weighted Cox proportional hazards models were used to estimate marginal HRs and 95% CIs. In the early-event analysis, IBD diagnoses were assessed within the first 2 years of treatment initiation, an analysis subject to potential protopathic bias. In the late-event analysis, all exposures were lagged by 2 years to account for latency and minimise protopathic bias.

Results

In the early-event analysis, the use of PPIs was associated with an increased risk of IBD within the first 2 years of treatment initiation, compared with H2RAs (HR 1.39, 95% CI 1.14 to 1.69). In contrast, the use of PPIs was not associated with an increased risk of IBD in the late-event analysis (HR 1.05, 95% CI 0.90 to 1.22). The results remained consistent in several sensitivity analyses.

Conclusions

Compared with H2RAs, PPIs were not associated with an increased risk of IBD, after accounting for protopathic bias.