bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Review of Household Transmission of Strep A: A Potential Site for Prevention That Has Eluded Attention
Authors: Enkel Stephanie L , Barnes Samuel , Daw Jessica , Pearson Emma , Thomas Hannah M M , Lansbury Nina , Wyber Rosemary , Redmond Andrew M , Ralph Anna P , Carapetis Jonathan R , Bowen Asha C
Published: March 2024

Background

Although Streptococcus pyogenes (Strep A) is the sixth-most common infectious disease globally, its transmission within the household remains an understudied driver of infection. We undertook a systematic review to better understand the transmission of Strep A among people within the home, while highlighting opportunities for prevention.

Methods

A search strategy was applied to 5 databases between September 2022 and March 2023. Results were limited to articles published between January 2000 and March 2023. Texts were reviewed by 2 authors and the following data extracted: article details (title, author, year), study type, transmission year, country, participant age, infection status, molecular testing, and transmission mode. Funding was provided by the Australian National Health and Medical Research Council (GNT2010716).

Results

The final analysis comprised 28 texts. Only 7 studies (25.0%) provided sufficient detail to identify the Strep A transmission mode: contact (n = 4), vehicle (bedding, clothing, other fabric, and medical equipment; n = 2), and contact with animals (n = 1). All others were classified as household (specific mode unascertainable). Most articles reported outbreaks involving invasive Strep A infections.

Conclusions

There is limited literature regarding household transmission of Strep A. Understanding transmission in this setting remains imperative to guide control methods.
Assessing silver nanoparticle and antimicrobial combinations for antibacterial activity and biofilm prevention on surgical sutures
Authors: Al-Sawarees Diana K , Darwish Rula M , Abu-Zurayk Rund , Masri Mahmoud Al
Published: March 2024

Aims

To evaluate the effect of silver nanoparticles alone and in combination with Triclosan, and trans-cinnamaldehyde against Staphylococcus aureus and Escherichia coli biofilms on sutures to improve patients’ outcomes.

Methods and results

Silver nanoparticles were prepared by chemical method and characterized by UV–visible spectrophotometer and dynamic light scattering. The minimum inhibitory concentration was assessed by the Microdilution assay. The antibiofilm activity was determined using crystal violet assay. A checkerboard assay using the fractional inhibitory concentration index and time-kill curve was used to investigate the synergistic effect of silver nanoparticle combinations. The hemolytic activity was determined using an erythrocyte hemolytic assay. Our results revealed that silver nanoparticles, Triclosan, and trans-cinnamaldehyde (TCA) inhibited S.aureus and E.coli biofilms. Silver nanoparticles with TCA showed a synergistic effect (FICI values 0.35 and 0.45 against S. aureus and E. coli biofilms, respectively), and silver nanoparticles with Triclosan showed complete inhibition of S. aureus biofilm. The hemolytic activity was <2.50% for the combinations.
Smelly shark, smelly ray: what is infecting you?
Authors: Cardoso Maíra Duarte , Maciel Oswaldo Luiz de C , de Souza André Luiz Medeiros , Roges Emily Moraes , Gonçalves Verônica Dias , Siciliano Salvatore , Rodrigues Dália dos Prazeres , Hauser-Davis Rachel Ann
Published: March 2024

Aims

Although elasmobranchs are consumed worldwide, bacteriological assessments for this group are still sorely lacking. In this context, this study assessed bacteria of sharks and rays from one of the most important landing ports along the Rio de Janeiro coast.

Methods and results

Bacteria were isolated from the cloacal swabs of the sampled elasmobranchs. They were cultured, and Vibrio, Aeromonas, and Enterobacterales were isolated and identified. The isolated bacteria were then biochemically identified and antimicrobial susceptibility assays were performed. Antigenic characterizations were performed for Salmonella spp. and Polymerase Chain Reaction (PCR) assays were performed to identify Escherichia coli pathotypes. Several bacteria of interest in the One Health context were detected. The most prevalent Enterobacterales were Morganella morganii and Citrobacter freundii, while Vibrio harveyi and Vibrio fluvialis were the most prevalent among Vibrio spp. and Aeromonas allosacharophila and Aeromonas veronii bv. veronii were the most frequent among Aeromonas spp. Several bacteria also displayed antimicrobial resistance, indicative of Public Health concerns. A total of 10% of Vibrio strains were resistant to trimethoprim-sulfamethoxazole and 40% displayed intermediate resistance to cefoxitin. Salmonella enterica strains displayed intermediate resistance to ciprofloxacin, nalidixic acid and streptomycin. All V. cholerae strains were identified as non-O1/non-O139. The detected E. coli strains did not exhibit pathogenicity genes. This is the first study to perform serology assessments for S. enterica subsp. enterica isolated from elasmobranchs, identifying the zoonotic Typhimurium serovar. Salmonella serology evaluations are, therefore, paramount to identify the importance of elasmobranchs in the epidemiological salmonellosis chain.

Conclusions

The detection of several pathogenic and antibiotic-resistant bacteria may pose significant Public Health risks in Brazil, due to high elasmobranch consumption rates, indicating the urgent need for further bacteriological assessments in this group.
Cldn4overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway
Authors: Jie Huang , Jie Wang , Yingxue Guo , Xin Zhang , Runnan Xu , Wenjie Huang , Jianxiong Ma , Bodong Lv
Published: March 2024

Background

Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide.

Aim

Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs).

Methods

We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function.

Outcomes

Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function.

Results

We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function.

Clinical Implications

Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment.

Strengths and Limitations

Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines.

Conclusion

CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.
Changes in carbohydrate distribution in cotton photosynthetic organs and increase in boll weight reduce yield loss under high temperature
Authors: Yang Liuyan , Duan Jiahao , Liu Yu , Hu Wei , Liu Xingke , Wang Youhua , Zhou Zhiguo , Zhao Wenqing
Published: March 2024

Yield of cotton (Gossypium hirsutum) does not always fall with high temperature (HT) even though this induces significant reductions in fruit retention. To investigate the underlying mechanisms, a greenhouse experiment was conducted with two temperature regimes [control treatment, 28 °C; high temperature (HT), 34 °C] for 7 d. Results showed HT did not significantly influence cotton yield, but reduced boll number and increased boll weight. The 13C distribution ratio of the leaf subtending the cotton boll (LSCB) decreased while that of the cotton boll increased under HT. Transcriptomic and proteomic analyses of the LSCB revealed up-regulated genes involved in cytokinin and jasmonic acid synthesis, as well as SWEET15 (GH_D01G0218), which positively regulated photosynthesis and transport photosynthate, ultimately leading to increased boll weight. After 7 d recovery from HT, the 13C distribution ratio of the LSCB increased while that of the cotton boll decreased. However, boll weight still increased, which was related to increased amylase and sucrose phosphate synthase activities and up-regulated sucrose transport genes in the main-stem leaf and capsule wall. Thus, both accelerated sucrose synthesis and transport in the LSCB under HT and increased sucrose supply ability of the main-stem leaf and capsule wall after recovery from HT contributed to an increased boll weight, which finally maintained cotton yield.
Revealing the hidden interplay: The unexplored relationship between fungi and viruses beyond HIV, SARS-CoV-2, and influenza
Authors: Ghelfenstein-Ferreira Théo , Serris Alexandra , Salmona Maud , Lanternier Fanny , Alanio Alexandre
Published: March 2024

The complex interaction between viruses and fungi has profound implications, especially given the significant impact of these microorganisms on human health. While well-known examples such as HIV, influenza, and SARS-CoV-2 are recognized as risk factors for invasive fungal diseases, the relationship between viruses and fungi remains largely underexplored outside of these cases. Fungi and viruses can engage in symbiotic or synergistic interactions. Remarkably, some viruses, known as mycoviruses, can directly infect fungi, may influencing their phenotype and potentially their virulence. In addition, viruses and fungi can coexist within the human microbiome, a complex ecosystem of microorganisms. Under certain conditions, viral infection might predispose the host to an invasive fungal infection, as observed with influenza-associated pulmonary aspergillosis or COVID-19 associated pulmonary aspergillosis. We aim in this review to highlight potential connections between fungi and viruses (CMV and other herpesviruses, HTLV-1 and respiratory viruses), excluding SARS-CoV-2 and influenza.
VLBI astrometry of radio stars to link radio and optical celestial reference frames: observing strategies
Authors: Zhang Jingdong , Zhang Bo , Xu Shuangjing , Liu Niu , Chen Wen , Ding Hao , Jiang Pengfei , Sun Yan , Wang Jinqing , Cui Lang , Wen Shiming , Mai Xiaofeng , Li Jinling , Shu Fengchun , Huang Yidan
Published: March 2024

The Gaia celestial reference frame (Gaia-CRF) will benefit from a close assessment with independent methods, such as Very Long Baseline Interferometry (VLBI) measurements of radio stars at bright magnitudes. However, obtaining full astrometric parameters for each radio star through VLBI measurements demands a significant amount of observation time. This study proposes an efficient observing strategy that acquires double-epoch VLBI positions to measure the positions and proper motions of radio stars at a reduced cost. The solution for CRF link compatible with individual VLBI position measurements is introduced, and the optimized observing epoch scheduling is discussed. Applying this solution to observational data yields results sensitive to sample increase or decrease, yet they remain consistently in line with the literature at the 1σ level. This suggests the potential for improvement with a larger sample size. Simulations show that the double-epoch strategy reduces CRF link parameter uncertainties by over 30 per cent compared to the five-parameter strategy.
On stellar migration from Andromeda to the Milky Way
Authors: Gülzow Lukas , Fairbairn Malcolm , Schwarz Dominik J
Published: March 2024

Recent Gaia observations suggest that some hypervelocity stars (HVSs) might originate from outside the Galaxy. We ask whether these HVSs could come from as far as Andromeda. Therefore, we simulate HVSs originating in Andromeda with initial conditions based on attributes of high-velocity stars measured in the Milky Way and a simple model for the gravitational potential of Andromeda and the Milky Way. We evaluate the validity of this scenario based on the simulation results. While we expect that the vast majority of HVSs in our Galaxy will originate here, we expect the number of stars present from Andromeda at any one time to be between 12 and 3910, depending upon model assumptions. Further, we analyse the properties of HVSs that are able to reach the Milky Way. We discuss whether they could be detected experimentally based on recent constraints set on the ejection rate of HVSs from the Milky Way centre.
Predicting the linear response of self-gravitating stellar spheres and discs with LinearResponse.jl
Authors: Petersen Michael S , Roule Mathieu , Fouvry Jean-Baptiste , Pichon Christophe , Tep Kerwann
Published: March 2024

We present LinearResponse.jl, an efficient, versatile public library written in julia to compute the linear response of self-gravitating (three-dimensional spherically symmetric) stellar spheres and (two-dimensional axisymmetric razor-thin) discs. LinearResponse.jl can scan the whole complex frequency plane, probing unstable, neutral and (weakly) damped modes. Given a potential model and a distribution function, this numerical toolbox estimates the modal frequencies as well as the shapes of individual modes. The libraries are validated against a combination of previous results for the spherical isochrone model and Mestel discs, and new simulations for the spherical Plummer model. Beyond linear response theory, the realm of applications of LinearResponse.jl also extends to the kinetic theory of self-gravitating systems through a modular interface.
Reinterpreting fundamental plane correlations with machine learning
Authors: Schafer Chad , Singh Sukhdeep , Jagvaral Yesukhei
Published: March 2024

This work explores the relationships between galaxy sizes and related observable galaxy properties in a large volume cosmological hydrodynamical simulation. The objectives of this work are to develop a better understanding of both the correlations between galaxy properties and the influence of environment on galaxy physics in order to build an improved model for the galaxy sizes, building off of the fundamental plane. With an accurate intrinsic galaxy size predictor, the residuals in the observed galaxy sizes can potentially be used for multiple cosmological applications, including making measurements of galaxy velocities in spectroscopic samples, estimating the rate of cosmic expansion, and constraining the uncertainties in the photometric redshifts of galaxies. Using projection pursuit regression, the model accurately predicts intrinsic galaxy sizes and have residuals which have limited correlation with galaxy properties. The model decreases the spatial correlation of galaxy size residuals by a factor of ∼5 at small scales compared to the baseline correlation when the mean size is used as a predictor.
Determinants of CRISPR Cas12a nuclease activation by DNA and RNA targets
Authors: Nalefski Eric A , Kooistra Remy M , Parikh Ishira , Hedley Samantha , Rajaraman Karunya , Madan Damian
Published: March 2024

The RNA-guided CRISPR-associated (Cas) enzyme Cas12a cleaves specific double-stranded (ds-) or single-stranded (ss-) DNA targets (in cis), unleashing non-specific ssDNA cleavage (in trans). Though this trans-activity is widely coopted for diagnostics, little is known about target determinants promoting optimal enzyme performance. Using quantitative kinetics, we show formation of activated nuclease proceeds via two steps whereby rapid binding of Cas12a ribonucleoprotein to target is followed by a slower allosteric transition. Activation does not require a canonical protospacer-adjacent motif (PAM), nor is utilization of such PAMs predictive of high trans-activity. We identify several target determinants that can profoundly impact activation times, including bases within the PAM (for ds- but not ssDNA targets) and sequences within and outside those complementary to the spacer, DNA topology, target length, presence of non-specific DNA, and ribose backbone itself, uncovering previously uncharacterized cleavage of and activation by RNA targets. The results provide insight into the mechanism of Cas12a activation, with direct implications on the role of Cas12a in bacterial immunity and for Cas-based diagnostics.
Molecular mechanism of the one-component regulator RccR on bacterial metabolism and virulence
Authors: Zhu Yibo , Mou Xingyu , Song Yingjie , Zhang Qianqian , Sun Bo , Liu Huanxiang , Tang Hong , Bao Rui
Published: March 2024

The regulation of carbon metabolism and virulence is critical for the rapid adaptation of pathogenic bacteria to host conditions. In Pseudomonas aeruginosa, RccR is a transcriptional regulator of genes involved in primary carbon metabolism and is associated with bacterial resistance and virulence, although the exact mechanism is unclear. Our study demonstrates that PaRccR is a direct repressor of the transcriptional regulator genes mvaU and algU. Biochemical and structural analyses reveal that PaRccR can switch its DNA recognition mode through conformational changes triggered by KDPG binding or release. Mutagenesis and functional analysis underscore the significance of allosteric communication between the SIS domain and the DBD domain. Our findings suggest that, despite its overall structural similarity to other bacterial RpiR-type regulators, RccR displays a more complex regulatory element binding mode induced by ligands and a unique regulatory mechanism.
Klotho in pregnancy and intrauterine development—potential clinical implications: a review from the European Renal Association CKD-MBD Working Group
Authors: Kanbay Mehmet , Mutlu Ali , Bakir Cicek N , Peltek Ibrahim B , Canbaz Ata A , Díaz Tocados Juan Miguel , Haarhaus Mathias
Published: March 2024

Intrauterine development is crucial for life-long health; therefore, elucidation of its key regulators is of interest for their potential prognostic and therapeutic implications. Originally described as a membrane-bound anti-aging protein, Klotho has evolved as a regulator of numerous functions in different organ systems. Circulating Klotho is generated by alternative splicing or active shedding from cell membranes. Recently, Klotho was identified as a regulator of placental function, and while Klotho does not cross the placental barrier, increased levels of circulating α-Klotho have been identified in umbilical cord blood compared with maternal blood, indicating that Klotho may also play a role in intrauterine development. In this narrative review, we discuss novel insights into the specific functions of the Klotho proteins in the placenta and in intrauterine development, while summarizing up-to-date knowledge about their structures and functions. Klotho plays a role in stem cell functioning, organogenesis and haematopoiesis. Low circulating maternal and foetal levels of Klotho are associated with preeclampsia, intrauterine growth restriction, and an increased perinatal risk for newborns, indicating a potential use of Klotho as biomarker and therapeutic target. Experimental administration of Klotho protein indicates a neuro- and nephroprotective potential, suggesting a possible future role of Klotho as a therapeutic agent. However, the use of Klotho as intervention during pregnancy is as yet unproven. Here, we summarize novel evidence, suggesting Klotho as a key regulator for healthy pregnancies and intrauterine development with promising potential for clinical use.
Burnout and career satisfaction in young neuro-oncology investigators: Results of the Society for Neuro-Oncology Young Investigator Survey
Authors: Youssef Gilbert , Acquaye-Mallory Alvina , Vera Elizabeth , Chheda Milan G , Dunn Gavin P , Moliterno Jennifer , O’Brien Barbara J , Venere Monica , Yust-Katz Shlomit , Lee Eudocia Q , Armstrong Terri S
Published: March 2024

Background

Burnout is a syndrome characterized by emotional exhaustion, depersonalization, and a reduced sense of accomplishment, which commonly arises from chronic workplace stress in the medical field. Given the higher risk of burnout in younger age groups reported in some studies, the Society for Neuro-Oncology (SNO) Young Investigator (YI) and Wellness Committees combined efforts to examine burnout in the SNO YI membership to better understand and address their needs.

Methods

We distributed an anonymous online survey to SNO members in 2019. Only those meeting the definition of a YI were asked to complete the survey. The survey consisted of questions about personal and professional characteristics as well as the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS) questionnaire. Statistical analyses included descriptive statistics, univariate and multivariate analyses, and incorporation of previously defined burnout profiles.

Results

Data were analyzed for 173 participants who self-identified as YI. Measures of burnout showed that YI members scored higher on emotional exhaustion and depersonalization compared to normative population but similar to those in a prior SNO general membership survey. With respect to burnout profiles, 30% of YI respondents classified as overextended and 15% as burnout. Organizational challenges were the most common contributors to stress.

Conclusions

Similar to results from a previous survey completed by general SNO membership, the prevalence of burnout among neuro-oncology clinical and research YI is high, and is mainly characterized by overextension, warranting interventions at institutional and organizational levels.
Syphilis Treatment: Systematic Review and Meta-Analysis Investigating Nonpenicillin Therapeutic Strategies
Authors: Callado Gustavo Yano , Gutfreund Maria Celidonio , Pardo Isabele , Hsieh Mariana Kim , Lin Vivian , Sampson Mindy Marie , Nava Guillermo Rodriguez , Marins Tássia Aporta , Deliberato Rodrigo Octávio , Martino Marinês Dalla Valle , Holubar Marisa , Salinas Jorge L , Marra Alexandre R
Published: March 2024

Background

Penicillin's long-standing role as the reference standard in syphilis treatment has led to global reliance. However, this dependence presents challenges, prompting the need for alternative strategies. We performed a systematic literature review and meta-analysis to evaluate the efficacy of these alternative treatments against nonneurological syphilis.

Methods

We searched MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science from database inception to 28 August 2023, and we included studies that compared penicillin or amoxicillin monotherapy to other treatments for the management of nonneurological syphilis. Our primary outcome was serological cure rates. Random-effect models were used to obtain pooled mean differences, and heterogeneity was assessed using the I2 test.

Results

Of 6478 screened studies, 27 met the inclusion criteria, summing 6710 patients. The studies were considerably homogeneous, and stratified analyses considering each alternative treatment separately revealed that penicillin monotherapy did not outperform ceftriaxone (pooled odds ratio, 1.66 [95% confidence interval, .97–2.84]; I2 = 0%), azithromycin (0.92; [.73–1.18]; I2 = 0%), or doxycycline (0.82 [.61–1.10]; I2 = 1%) monotherapies with respect to serological conversion.

Conclusions

Alternative treatment strategies have serological cure rates equivalent to penicillin, potentially reducing global dependence on this antibiotic.
A nanopore-based cucumber genome assembly reveals structural variations at two QTLs controlling hypocotyl elongation
Authors: Liu Bin , Shen Cheng-Cheng , Xia Shi-Wei , Song Shan-Shan , Su Li-Hong , Li Yu , Hao Qian , Liu Yan-Jun , Guan Dai-Lu , Wang Ning , Wang Wen-Jiao , Zhao Xiang , Li Huan-Xiu , Li Xi-Xiang , Lai Yun-Song
Published: March 2024

The Xishuangbanna (XIS) cucumber (Cucumis sativus var. xishuangbannanesis) is a semiwild variety that has many distinct agronomic traits. Here, long reads generated by Nanopore sequencing technology helped assembling a high-quality genome (contig N50 = 8.7 Mb) of landrace XIS49. A total of 10,036 structural/sequence variations (SVs) were identified when comparing with Chinese Long (CL), and known SVs controlling spines, tubercles, and carpel number were confirmed in XIS49 genome. Two QTLs of hypocotyl elongation under low light, SH3.1 and SH6.1, were fine-mapped using introgression lines (donor parent, XIS49; recurrent parent, CL). SH3.1 encodes a red-light receptor Phytochrome B (PhyB, CsaV3_3G015190). A ∼4 kb region with large deletion and highly divergent regions (HDRs) were identified in the promoter of the PhyB gene in XIS49. Loss of function of this PhyB caused a super-long hypocotyl phenotype. SH6.1 encodes a CCCH-type zinc finger protein FRIGIDA-ESSENTIAL LIKE (FEL, CsaV3_6G050300). FEL negatively regulated hypocotyl elongation but it was transcriptionally suppressed by long terminal repeats retrotransposon insertion in CL cucumber. Mechanistically, FEL physically binds to the promoter of CONSTITUTIVE PHOTOMORPHOGENIC 1a (COP1a), regulating the expression of COP1a and the downstream hypocotyl elongation. These above results demonstrate the genetic mechanism of cucumber hypocotyl elongation under low light.
Genetic engineering of drought- and salt-tolerant tomato via Δ1-pyrroline-5-carboxylate reductase S-nitrosylation
Authors: Liu Wei , Wei Jin-Wei , Shan Qing , Liu Minghui , Xu Jinghao , Gong Biao
Published: March 2024

Drought and soil salinization substantially impact agriculture. While proline’s role in enhancing stress tolerance is known, the exact molecular mechanism by which plants process stress signals and control proline synthesis under stress is still not fully understood. In tomato (Solanum lycopersicum L.), drought and salt stress stimulate nitric oxide (NO) production, which boosts proline synthesis by activating Δ1-pyrroline-5-carboxylate synthetase (SlP5CS) and Δ1-pyrroline-5-carboxylate reductase (SlP5CR) genes and the P5CR enzyme. The crucial factor is stress-triggered NO production, which regulates the S-nitrosylation of SlP5CR at Cys-5, thereby increasing its NAD(P)H affinity and enzymatic activity. S-nitrosylation of SlP5CR enables tomato plants to better adapt to changing NAD(P)H levels, boosting both SlP5CR activity and proline synthesis during stress. By comparing tomato lines genetically modified to express different forms of SlP5CR, including a variant mimicking S-nitrosylation (SlP5CRC5W), we found that SlP5CRC5W plants show superior growth and stress tolerance. This is attributed to better P5CR activity, proline production, water use efficiency, reactive oxygen species scavenging, and sodium excretion. Overall, this study demonstrates that tomato engineered to mimic S-nitrosylated SlP5CR exhibits enhanced growth and yield under drought and salt stress conditions, highlighting a promising approach for stress-tolerant tomato cultivation.
Peroxisomal 4-coumaroyl-CoA ligases participate in shikonin production in Lithospermum erythrorhizon
Authors: Nakanishi Kohei , Li Hao , Ichino Takuji , Tatsumi Kanade , Osakabe Keishi , Watanabe Bunta , Shimomura Koichiro , Yazaki Kazufumi
Published: March 2024

4-Coumaroyl-CoA ligase (4CL) is a key enzyme in the phenylpropanoid pathway, which is involved in the biosynthesis of various specialized metabolites such as flavonoids, coumarins, lignans, and lignin. Plants have several 4CLs showing divergence in sequence: Class I 4CLs involved in lignin metabolism, Class II 4CLs associated with flavonoid metabolism, and atypical 4CLs and 4CL-like proteins of unknown function. Shikonin, a Boraginaceae-specific specialized metabolite in red gromwell (Lithospermum erythrorhizon), is biosynthesized from p-hydroxybenzoic acid, and the involvement of 4CL in its biosynthesis has long been debated. In this study, we demonstrated the requirement of 4CL for shikonin biosynthesis using a 4CL-specific inhibitor. In silico analysis of the L. erythrorhizon genome revealed the presence of at least 8 4CL genes, among which the expression of 3 (Le4CL3, Le4CL4, and Le4CL5) showed a positive association with shikonin production. Phylogenetic analysis indicated that Le4CL5 belongs to Class I 4CLs, while Le4CL3 and Le4CL4 belong to clades that are distant from Class I and Class II. Interestingly, both Le4CL3 and Le4CL4 have peroxisome targeting signal 1 in their C-terminal region, and subcellular localization analysis revealed that both localize to the peroxisome. We targeted each of the 3 Le4CL genes by CRISPR/Cas9-mediated mutagenesis and observed remarkably lower shikonin production in Le4CL3-ge and Le4CL4-ge genome-edited lines compared with the vector control. We, therefore, conclude that peroxisomal Le4CL3 and Le4CL4 are responsible for shikonin production and propose a model for metabolite-specific 4CL distribution in L. erythrorhizon.
Transcription factor OsWRKY72 controls rice leaf angle by regulating LAZY1-mediated shoot gravitropism
Authors: Liu Lei , Zhao Lirong , Liu Yunwei , Zhu Yi , Chen Shidie , Yang Lu , Li Xia , Chen Wanqin , Xu Zhiyu , Xu Peng , Wang Houping , Yu Diqiu
Published: March 2024

Leaf angle is a major trait of ideal architecture, which is considered to influence rice (Oryza sativa) cultivation and grain yield. Although a few mutants with altered rice leaf inclination angles have been reported, the underlying molecular mechanism remains unclear. In this study, we showed that a WRKY transcription factor gene, OsWRKY72, was highly expressed in the leaf sheath and lamina joint. Phenotypic analyses showed that oswrky72 mutants had smaller leaf angles than the wild type, while OsWRKY72 overexpression lines exhibited an increased leaf angle. This observation suggests that OsWRKY72 functions as a positive regulator, promoting the enlargement of the leaf angle. Our bioinformatics analysis identified LAZY1 as the downstream gene of OsWRKY72. Electrophoretic mobility shift assays and dual-luciferase analysis revealed that OsWRKY72 directly inhibited LAZY1 by binding to its promoter. Moreover, knocking out OsWRKY72 enhanced shoot gravitropism, which contrasted with the phenotype of lazy1 plants. These results imply that OsWRKY72 regulates the leaf angle through gravitropism by reducing the expression of LAZY1. In addition, OsWRKY72 could directly regulate the expression of other leaf angle–related genes such as FLOWERING LOCUS T-LIKE 12 (OsFTL12) and WALL-ASSOCIATED KINASE 11 (OsWAK11). Our study indicates that OsWRKY72 contributes positively to the expansion of the leaf angle by interfering with shoot gravitropism in rice.
Early complications of a novel retrograde intramedullary femoral nail in the treatment of femur fractures
Authors: Cinats David J. , Bashir Azhar , Toney Clarence B. , Satpathy Jibanananda , Kates Stephen L. , Perdue Paul W.
Published: March 2024

OBJECTIVES:

To determine the early implant failure rate of a novel retrograde intramedullary femoral nail

METHODS:

Design: Retrospective matched case control

Setting:

Academic level 1 trauma center

Patients Selection Criteria:

Patients 18 years and older with an acute AO/OTA 32-A, 32-B, 32-C, and 33-A fracture or periprosthetic distal femur fracture from April 2018 to April 2022 were included in the study. The two interventions compared were the Synthes Expert Retrograde/antegrade femoral nail (RAFN or control implant) versus the next generation RFN-Advanced retrograde femoral nail (RFNA or experimental implant) (Synthes, West Chester, PA).

Outcome Measures and Comparisons: Early implanted-related complications between the experimental and control implants were assessed including locking screw backout, screw breakage, intramedullary nail failure, need for secondary surgery, and loss of fracture reduction

RESULTS:

314 patients were identified with a mean age of 31.0 years and 62.4% of the patients being male. Open fractures occurred in 32.5% of patients with 3.8% of injuries being distal femur periprosthetic fractures. 56 patients in the experimental group and 258 patients in the control group. Mean follow-up was 46.8 weeks for the control cohort and 21.0 weeks for the experimental cohort. Distal interlocking screw backout occurred in 23.2% [13 of 56] of experimental group patients and 1.9% [5 of 258] of control group patients (p<0.0001). Initial diagnosis of interlocking screw back out occurred at an average of 3.2 weeks post-operatively (range, 2-12 weeks). 54% of patients that sustained screw back-out underwent a secondary operation to remove the symptomatic screws (12.5% of all patients treated with the experimental implant required an unplanned secondary operation due to screw backout). A logistic regression model was used to predict screw back out and found the experimental implant group was 4.3 times as likely to experience distal locking screw backout compared to the control group (p=0.01).

CONCLUSIONS:

The RFNA implant was associated with a significantly higher rate of screw back-out with a substantial number of unplanned secondary surgeries compared to the previous generation of this implant.

LEVEL OF EVIDENCE:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Fontan-Associated Liver Disease: A Review
Authors: Heering Gabriel , Lebovics Nachum , Agarwal Raksheeth , Frishman William H. , Lebovics Edward
Published: March 2024

Fontan-associated liver disease (FALD) is a chronic complication of the Fontan procedure, a palliative surgery for patients with congenital heart disease that results in a single-ventricle circulation. The success of the Fontan procedure has led to a growing population of post-Fontan patients living well into adulthood. For this population, FALD is a major cause of morbidity and mortality. It encompasses a spectrum of hepatic abnormalities, ranging from mild fibrosis to cirrhosis and hepatocellular carcinoma. The pathophysiology of FALD is multifactorial, involving hemodynamic and inflammatory factors. The diagnosis and monitoring of FALD present many challenges. Conventional noninvasive tests that use liver stiffness as a surrogate marker of fibrosis are unreliable in FALD, where liver stiffness is also a result of congestion due to the Fontan circulation. Even invasive tissue sampling is inconsistent due to the patchy distribution of fibrosis. FALD is also associated with both benign and malignant liver lesions, which may exhibit similar imaging features. There is therefore a need for validated diagnostic and surveillance protocols to address these challenges. The definitive treatment of end-stage FALD is also a subject of controversy. Both isolated heart transplantation and combined heart-liver transplantation have been employed, with the latter becoming increasingly preferred in the US. This article reviews the current literature on the epidemiology, pathophysiology, diagnosis, and management of FALD, and highlights knowledge gaps that require further research.
Landiolol for Treating Arrhythmias: A State-of-The-Art Review
Authors: Ghallab Muhammad , Ahmed Mahmoud Samy , Ostrow Talia H. , Rasool Muhammad Haseeul , Alagha Zakaria , Miller Daniel , Frishman William H. , Aronow Wilbert S , Frenkel Daniel
Published: March 2024

This article provides a state-of-the-art review on landiolol, a medication that was recently submitted for 7 approvals. Focusing on its pharmacology, pharmacokinetics, and pharmacodynamics, the analysis underscores landiolol’s unique attributes compared to conventional beta-blockers, particularly esmolol. As a sympatholytic agent, landiolol exhibits a short half-life, high cardioselectivity, and minimal impact on blood pressure, setting it apart in the realm of arrhythmia treatment. The review explores landiolol’s potential applications, emphasizing scenarios where other beta-blockers may be limited. A detailed examination of its efficacy in preventing postoperative atrial fibrillation reveals promising results from clinical trials, suggesting its utility in diverse surgical settings. Additionally, the article delves into landiolol’s role in rate control for atrial fibrillation/flutter, treatment of ventricular tachycardia/fibrillation, and its use in managing sepsis-related tachyarrhythmias. The evolving landscape of landiolol’s applications extends beyond cardiac care, including potential anti-inflammatory, antioxidative, analgesic, and anticancer effects. While the outcomes from various studies are promising, challenges persist, requiring further research to optimize dosing strategies, identify optimal patient populations, and elucidate mechanisms underlying its diverse effects. The potential expansion of landiolol’s applications highlights the importance of ongoing clinical investigation, offering a promising avenue for enhancing arrhythmia management and addressing broader medical needs.
Striding Toward Cardiovascular Health: The Impact of Step Counts on Heart Wellness
Authors: Goyal Anjali , Frishman William
Published: March 2024

In an era characterized by sedentary lifestyles, cardiovascular diseases pose a significant global health challenge. As preventive healthcare strategies evolve, this article explores the tangible and accessible metric of step counts and their implications for cardiovascular health. The review provides insights into potential benefits, challenges, and future directions in promoting physical activity for heart wellness.
Durable Approaches to Recurrent Rectal Prolapse Repair May Require Avoidance of Index Procedure
Authors: Bordeianou Liliana , Ogilvie James W. , Saraidaridis Julia T , Olortegui Kinga S. , Ratto Carlo , Ky Alex J. , Oliveira Lucia , Vogler Sarah A. , Gurland Brooke H. ,   On behalf of the Steering Committee for the Pelvic Floor Disorders Consortium Quality Improvement in Rectal Prolapse Surgery Database Pilot
Published: March 2024

BACKGROUND:

Surgical treatment of recurrent rectal prolapse is associated with unique technical challenges, partly determined by the surgical approach utilized for the index operation. Success rates are variable and data to determine the best approach in patients with recurring prolapse are lacking.

OBJECTIVE:

To assess current surgical approaches to patients with prior rectal prolapse repairs and to compare short-term outcomes of de novo and redo procedures, including recurrence of rectal prolapse.

DESIGN:

Retrospective analysis of a prospective database.

SETTING:

The Multicenter Pelvic Floor Disorders Consortium Prospective Quality Improvement database. Deidentified surgeons at more than 25 sites (81% high volume) self-reported patient demographics, prior repairs, symptoms of incontinence and obstructed defecation, and operative details, including history of concomitant repairs and prior prolapse repairs.

INTERVENTIONS:

Incidence and type of repair used for prior rectal prolapse surgery were recorded. Primary and secondary outcomes of index and redo operations were calculated. Patients undergoing rectal prolapse re-repair (redo) were compared to patients undergoing first (de novo) rectal prolapse repair. The incidence of rectal prolapse recurrence in de novo and redo operations was quantified.

OUTCOMES:

The primary outcome of rectal prolapse recurrence in de novo and redo settings.

RESULTS:

Eighty-nine (19.3%) of 461 patients underwent redo rectal prolapse repair. On short-term follow-up, redo patients had prolapse recurrence rates similar to those undergoing de novo repair. However, patients undergoing redo procedures rarely had the same operation as their index procedure.

LIMITATIONS:

Self-reported, de-identified data.

CONCLUSIONS/DISCUSSION:

Our results suggest that recurrent rectal prolapse surgery is feasible and can offer adequate rates of rectal prolapse durability in the short term but may argue for a change in surgical approach for redo procedures when clinically feasible. See Video Abstract.
Exploring autism spectrum disorder (ASD) and attention deficit disorder (ADD/ADHD) in children exposed to polybrominated biphenyl
Authors: Christensen Grace M. , Terrell Metrecia L. , Pearce Brad D. , Hood Robert B. , Barton Hillary , Pearson Melanie , Marcus Michele
Published: March 2024

Background:

Although the causes of attention-deficit/hyperactivity disorder (ADHD) and autism have not been identified, exposure to endocrine-disrupting chemicals, such as polybrominated biphenyl (PBB), during fetal development and early life has been suspected to impact neurological development. This study aims to investigate the association between prenatal and early life exposure to PBB and the development of ADHD and autism later in life.

Methods:

Data from the Michigan PBB Registry, a cohort of Michigan residents who had been exposed to PBB in a mass contamination event in 1973, was leveraged for this nested case-control analysis among two distinct samples: (1) Those who self-reported ADHD or autism diagnosis, and (2) mothers who reported their child’s ADHD or autism diagnosis. PBB exposure was measured in participants of the PBB Registry, and the mother’s PBB level was used in mother-reported analyses. Cases were matched with controls by sex and year of birth. Conditional logistic regression models were used to estimate the association between PBB level and case status.

Results:

PBB levels were higher among those who were exposed in early life compared with those exposed in utero (geometric mean: 0.300 ng/ml vs. 0.016 ng/ml). Among women in this cohort, a higher than expected proportion of self-reported ADHD diagnosis (11.11%), compared with population estimates. PBB was not associated with ADHD or autism in either self-reported or mother-reported analyses.

Conclusions:

This study adds to the sparse literature about prenatal and early life exposure to PBB-153 and ADHD and autism. Future studies should examine potential effect modification by sex.
Proparacaine Overuse in Corneal Abrasions at the Emergency Department: A Case Series
Authors: Zhou Avery , Rabljenovic Anja , Steinemann Thomas L.
Published: March 2024

Corneal abrasions are among the most common ophthalmic injuries in the emergency department (ED) and primarily present as severe ocular pain. Topical anesthetics provide temporary analgesia, but overuse is associated with complications including further corneal injury, infection, and vision loss. This case series describes three patients who used a 15-mL bottle of 0.05% proparacaine hydrochloride ophthalmic solution after discharge from the ED and returned within three days with corneal injury and pain. Although the use of topical anesthetics is traditionally discouraged by ophthalmologists, publications in the emergency medicine literature support their use. We review the literature surrounding topical anesthetic use in the ED setting and caution against prescribing patients topical anesthetics for corneal abrasions, particularly without patient counseling and significant restriction of anesthetic supply.
Workplace Psychosocial Factors, Work Organization, and Physical Exertion as Risk Factors for Low Back Pain Among US Workers
Authors: Shockey Taylor , Alterman Toni , Yang Haiou , Lu Ming-Lun
Published: March 2024

Objective

To evaluate the association between workplace psychosocial, organization, and physical risk factors with low back pain (LBP) among US workers.

Methods

2015 National Health Interview Survey data were analyzed to calculate the prevalence rates and prevalence ratios for LBP across levels of workplace psychosocial and organizational risk factors among 17,464 US adult workers who worked ≥20 hours per week. Results were also stratified by workplace physical exertion.

Results

The adjusted prevalence rates of LBP were significantly elevated for workers reporting high job demand, low job control, work-family imbalance, bullying, job insecurity, working alternate shifts, and physical exertion. Job control and nonstandard shifts were significantly associated with LBP only among those who reported low/no physical exertion.

Conclusions

LBP prevalence was associated with select workplace psychosocial and organization risk factors. Stratification by physical exertion modified multiple associations.
Four-Point Impedance: A Potential Biomarker for Residual Hearing After Cochlear Implantation
Authors: Tan Eren , Bester Christofer , Collins Aaron , Razmovski Tayla , O'Leary Stephen
Published: March 2024

Introduction

Preservation of residual hearing after cochlear implantation allows for electroacoustic stimulation, which leads to better music appreciation, noise localization, and speech comprehension in noisy environments. Real-time intraoperative electrocochleography (rt-ECochG) monitoring has shown promise in improving residual hearing rates. Four-point impedance (4PI) is being explored as a potential biomarker in cochlear implantation that has been associated with fibrotic tissue response, hearing loss, and dizziness. In this study, we explore whether monitoring both rt-ECochG intraoperatively and postoperative 4PI improves predictions of the preservation of residual hearing.

Methods

This was a prospective cohort study. Adults with residual acoustic hearing underwent cochlear implantation with intraoperative intracochlear electrocochleography (ECochG) monitoring. The surgeon responded to a drop in ECochG signal amplitude of greater than 30% by a standardized manipulation of the electrode with the aim of restoring the ECochG. At the end of the procedure, the ECochG signal was categorized as being maintained or having dropped more than 30%. 4PI was measured on 1 day, 1 week, and 1 and 3 months after cochlear implantation. Residual hearing was measured by routine pure-tone audiogram at 3 months postoperatively. The ECochG category and 4PI impedance values were entered as factors in a multiple linear regression predicting the protection of residual hearing.

Results

Twenty-six patients were recruited. Rt-ECochG significantly predicted residual hearing at 3 months (ttest; mean difference, 37.7%;p= 0.002). Inclusion of both 1-day or 3-month 4PI in a multiple linear regression with rt-ECochG markedly improved upon correlations with residual hearing compared with the rt-ECochG–only model (rt-ECochG and 1-d 4PI model,R2= 0.67; rt-ECochG and 3-mo 4PI model,R2= 0.72; rt-ECochG–only model,R2= 0.33).

Conclusions

Both rt-ECochG and 4PI predict preservation of residual hearing after cochlear implantation. These findings suggest that the biological response of the cochlea to implantation, as reflected in 4PI, is an important determinant of residual hearing, independent of the acute effects on hearing during implant surgery seen with rt-ECochG. We speculate that 4PI relates to inflammation 1 day after implantation and fibrosis at 3 months.