bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification and characterization of the produced hyaluronidase by Brucella Intermedia MEFS for antioxidant and anticancer applications
Authors: Ebraheem Mai A. , El-Fakharany Esmail M. , Husseiny Sherif Moussa , Mohammed Fafy A.
Published: July 2024

Hyaluronidase (hyase) is an endoglycosidase enzyme that degrades hyaluronic acid (HA) and is mostly known to be found in the extracellular matrix of connective tissues. In the current study, eleven bacteria isolates and one actinomycete were isolated from a roaster comb and screened for hyase production. Seven isolates were positive for hyase, and the most potent isolate was selected based on the diameter of the transparent zone. Based on the morphological, physiological, and 16 S rRNA characteristics, the most potent isolate was identified as Brucella intermedia MEFS with accession number OR794010. The environmental conditions supporting the maximum production of hyase were optimized to be incubation at 30 ºC for 48 h and pH 7, which caused a 1.17-fold increase in hyase production with an activity of 84 U/mL. Hyase was purified using a standard protocol, including precipitation with ammonium sulphate, DEAE as ion exchange chromatography, and size exclusion chromatography using Sephacryle S100, with a specific activity of 9.3-fold compared with the crude enzyme. The results revealed that the molecular weight of hyase was 65 KDa, and the optimum conditions for hyase activity were at pH 7.0 and 37 °C for 30 min. The purified hyase showed potent anticancer activities against colon, lung, skin, and breast cancer cell lines with low toxicity against normal somatic cells. The cell viability of hyase-treated cancer cells was found to be in a dose dependent manner. Hyase also controlled the growth factor-induced cell cycle progression of breast cancer cells and caused relative changes in angiogenesis-related genes as well as suppressed many pro-inflammatory proteins in MDA cells compared with 5-fluorouracil, indicating the significant role of hyase as an anticancer agent. In addition, hyase recorded the highest DPPH scavenging activity of 65.49% and total antioxidant activity of 71.84% at a concentration of 200 µg/mL.
Co-expression of a pair of interdependent regulators coding genes ovmZ and ovmW awakens the production of angucyclinones antibiotics in Streptomyces neyagawaensis
Authors: Li Junyue , Wang Kai , Luo Sainan , Tian Yuqing , Li Yue , Hu Songnian , Tan Huarong , Zhang Jihui , Li Jine
Published: July 2024

Background

Microbial genome sequencing and analysis revealed the presence of abundant silent secondary metabolites biosynthetic gene clusters (BGCs) in streptomycetes. Activating these BGCs has great significance for discovering new compounds and novel biosynthetic pathways.

Results

In this study, we found that ovmZ and ovmW homologs, a pair of interdependent transcriptional regulators coding genes, are widespread in actinobacteria and closely associated with the biosynthesis of secondary metabolites. Through co-overexpression of native ovmZ and ovmW in Streptomyces neyagawaensis NRRL B-3092, a silent type II polyketide synthase (PKS) gene cluster was activated to produce gephyromycin A, tetrangomycin and fridamycin E with the yields of 22.3 ± 8.0 mg/L, 4.8 ± 0.5 mg/L and 20.3 ± 4.1 mg/L respectively in the recombinant strain of S.ne/pZnWn. However, expression of either ovmZ or ovmW failed to activate this gene cluster. Interestingly, overexpression of the heterologous ovmZ and ovmW pair from oviedomycin BGC of S. ansochromogenes 7100 also led to awakening of this silent angucyclinone BGC in S. neyagawaensis.

Conclusion

A silent angucyclinone BGC was activated by overexpressing both ovmZ and ovmW in S. neyagawaensis. Due to the wide distribution of ovmZ and ovmW in the BGCs of actinobacteria, co-overexpression of ovmZ and ovmW could be a strategy for activating silent BGCs, thus stimulating the biosynthesis of secondary metabolites.
Effects of a cafeteria-based sustainable diet intervention on the adherence to the EAT-Lancet planetary health diet and greenhouse gas emissions of consumers: a quasi-experimental study at a large German hospital
Authors: Harrison Laura , Herrmann Alina , Quitmann Claudia , Stieglbauer Gabriele , Zeitz Christin , Franke Bernd , Danquah Ina
Published: July 2024

Background

Sustainable diets contribute to improving human health and reducing food-related greenhouse gas emissions (GHGE). Here, we established the effects of a facility-based sustainable diet intervention on the adherence to the EAT-Lancet Planetary Health Diet and GHGE of consumers.

Methods

In this quasi-experiment, vegan menus and educational material on sustainable diets were provided in the largest cafeteria of a German hospital for 3 months. Regular customers (> 1/week) in this cafeteria (intervention group) and in all other hospital cafeterias (control group) completed a questionnaire about their sociodemographic and dietary characteristics before and after the intervention period. We calculated difference-in-differences (DID), their 95% confidence intervals (CIs), and p-values for the adherence to the EAT-Lancet Planetary Health Diet Index (PHDI; 0–42 score points) and food-related GHGE. The protocol was registered at the German Clinical Trial Register (reference: DRKS00032620).

Findings

In this study population (N = 190; age range: 18–79 years; women: 67%; highest level of formal education: 63%), the mean baseline PHDI (25·1 ± 4·8 vs. 24·7 ± 5·8 points) and the mean baseline GHGE (3·3 ± 0·8 vs. 3·3 ± 0·7 kg CO2-eq./d) were similar between the intervention (n = 92) and the control group (n = 98). The PHDI increase was 0·6 points (95% CI: -0·4, + 1·6) higher in the intervention group than in the control group. This trend was stronger among frequent consumers of the vegan menu than among rare and never consumers. No between-group difference was seen for GHGE changes (DID: 0·0; 95% CI: -0·2, + 0·1 kg CO2-eq./d).

Interpretation

Pending verification in a longer-term project and a larger sample, this quasi-experiment in a big hospital in Germany suggests that offering vegan menus and information material in the cafeteria enhances the adherence to healthy and environmentally friendly diets among regular customers. These findings argue for making sustainable food choices the default option and for improving nutrition literacy.

Funding

Federal Ministry of Economic Affairs and Climate Action (BMWK), Else-Kröner-Fresenius Foundation (EKFS), Robert-Bosch Foundation (RBS).
Waiving the consent requirement to mitigate bias in observational precision medicine research
Authors: Song Ruifeng
Published: July 2024

Consent bias is a type of selection bias in biomedical research where those consenting to the research differ systematically from those not consenting. It is particularly relevant in precision medicine research because the complexity of these studies prevents certain subgroups from understanding, trusting, and consenting to the research. Because consent bias distorts research findings and causes inequitable distribution of research benefits, scholars propose two types of schemes to reduce consent bias: reforming existing consent models and removing the consent requirement altogether. This study explores the possibility of waiving consent in observational studies using existing data, because they involve fewer risks to participants than clinical trials if privacy safeguards are strengthened. It suggests that data protection mechanisms such as security enhancement and data protection impact assessment should be conducted to protect data privacy of participants in observational studies without consent.
Polymeric nanocarriers delivery systems in ischemic stroke for targeted therapeutic strategies
Authors: Zhu Lin , Zhong Weijie , Meng Xuchen , Yang Xiaosheng , Zhang Wenchuan , Tian Yayuan , Li Yi
Published: July 2024

Ischemic stroke is a complex, high-mortality disease with multifactorial etiology and pathogenesis. Currently, drug therapy is mainly used treat ischemic stroke in clinic, but there are still some limitations, such as limited blood-brain barrier (BBB) penetration efficiency, a narrow treatment time window and drug side effects. Recent studies have pointed out that drug delivery systems based on polymeric nanocarriers can effectively improve the insufficient treatment for ischemic stroke. They can provide neuronal protection by extending the plasma half-life of drugs, enhancing the drug’s permeability to penetrate the BBB, and targeting specific structures and cells. In this review, we classified polymeric nanocarriers used for delivering ischemic stroke drugs and introduced their preparation methods. We also evaluated the feasibility and effectiveness and discussed the existing limitations and prospects of polymeric nanocarriers for ischemic stroke treatment. We hoped that this review could provide a theoretical basis for the future development of nanomedicine delivery systems for the treatment of ischemic stroke.

Graphical Abstract
Chlorpromazine overcomes temozolomide resistance in glioblastoma by inhibiting Cx43 and essential DNA repair pathways
Authors: Matarrese Paola , Signore Michele , Ascione Barbara , Fanelli Giulia , Paggi Marco G. , Abbruzzese Claudia
Published: July 2024

Background

In the fight against GBM, drug repurposing emerges as a viable and time-saving approach to explore new treatment options. Chlorpromazine, an old antipsychotic medication, has recently arisen as a promising candidate for repositioning in GBM therapy in addition to temozolomide, the first-line standard of care. We previously demonstrated the antitumor efficacy of chlorpromazine and its synergistic effects with temozolomide in suppressing GBM cell malignant features in vitro. This prompted us to accomplish a Phase II clinical trial to evaluate the efficacy and safety of adding chlorpromazine to temozolomide in GBM patients with unmethylated MGMT gene promoter. In this in vitro study, we investigate the potential role of chlorpromazine in overcoming temozolomide resistance.

Methods

In our experimental set, we analyzed Connexin-43 expression at both the transcriptional and protein levels in control- and chlorpromazine-treated GBM cells. DNA damage and subsequent repair were assessed by immunofluorescence of γ-H2AX and Reverse-Phase Protein microArrays in chlorpromazine treated GBM cell lines. To elucidate the relationship between DNA repair systems and chemoresistance, we analyzed a signature of DNA repair genes in GBM cells after treatment with chlorpromazine, temozolomide and Connexin-43 downregulation.

Results

Chlorpromazine treatment significantly downregulated connexin-43 expression in GBM cells, consequently compromising connexin-dependent cellular resilience, and ultimately contributing to cell death. In line with this, we observed concordant post-translational modifications of molecular determinants involved in DNA damage and repair pathways. Our evaluation of DNA repair genes revealed that temozolomide elicited an increase, while chlorpromazine, as well as connexin-43 silencing, a decrease in DNA repair gene expression in GBM cells.

Conclusions

Chlorpromazine potentiates the cytotoxic effects of the alkylating agent temozolomide through a mechanism involving downregulation of Cx43 expression and disruption of the cell cycle arrest essential for DNA repair processes. This finding suggests that chlorpromazine may be a potential therapeutic strategy to overcome TMZ resistance in GBM cells by inhibiting their DNA repair mechanisms.
Association between number of confidants and adolescent anxiety/depression: a school-based study
Authors: Nishida Asuka , Foo Jerome Clifford , Yamaguchi Satoshi , Togo Fumiharu , Shimodera Shinji , Nishida Atsushi , Okazaki Yuji , Sasaki Tsukasa
Published: July 2024

Background

Having no or few confidants is found to be associated with more severe mental health problems and a higher prevalence of depression in adults, but research examining this association in adolescents is scarce. Social relationships may be particularly critical during adolescence, as it is an important developmental period during which vulnerability to mental health problems increases. The present study examined the relationship between having no or few confidants and anxiety/depressive symptoms in adolescents.

Methods

Cross-sectional self-report survey targeting 7–12th grade students (age range: 12–18) was conducted in public junior and senior high schools in Mie and Kochi, Japan. Data from 17,829 students (49.7% boys) were analyzed. Associations between anxiety/depressive symptoms (12-item General Health Questionnaire; score range: 0–12) and the number of confidants (None, 1–3, or ≥ 4) were examined using multilevel regression analyses. The analyses were stratified by gender and school level (junior/senior high), and adjusted for experiences of being physically abused and bullied and the interactions of these experiences with the number of confidants.

Results

Having no or 1–3 confidants was associated with more anxiety/depressive symptoms, compared to having ≥ 4 confidants (p < 0.001) in all stratified groups. Having no confidants was associated with more anxiety/depressive symptoms than having 1–3 confidants (p < 0.001); in senior high boys, no difference was observed between having no confidants and having 1–3 confidants. In addition, in senior high boys, victims of bullying who have confidants reported significantly less anxiety/depressive symptoms than the victims who have no confidants (p < 0.01).

Conclusions

Adolescents who had no or few confidants had more anxiety/depressive symptoms. Attention needs to be paid to better identify these adolescents, and avenues to support them need to be established.
Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers
Authors: Kabeer Farhia , Tran Hoa , Andronescu Mirela , Singh Gurdeep , Lee Hakwoo , Salehi Sohrab , Wang Beixi , Biele Justina , Brimhall Jazmine , Gee David , Cerda Viviana , O’Flanagan Ciara , Algara Teresa , Kono Takako , Beatty Sean , Zaikova Elena , Lai Daniel , Lee Eric , Moore Richard , Mungall Andrew J. ,   IMAXT Consortium, Williams Marc J. , Roth Andrew , Campbell Kieran R. , Shah Sohrab P. , Aparicio Samuel
Published: July 2024

Background

The encoding of cell intrinsic drug resistance states in breast cancer reflects the contributions of genomic and non-genomic variations and requires accurate estimation of clonal fitness from co-measurement of transcriptomic and genomic data. Somatic copy number (CN) variation is the dominant mutational mechanism leading to transcriptional variation and notably contributes to platinum chemotherapy resistance cell states. Here, we deploy time series measurements of triple negative breast cancer (TNBC) single-cell transcriptomes, along with co-measured single-cell CN fitness, identifying genomic and transcriptomic mechanisms in drug-associated transcriptional cell states.

Results

We present scRNA-seq data (53,641 filtered cells) from serial passaging TNBC patient-derived xenograft (PDX) experiments spanning 2.5 years, matched with genomic single-cell CN data from the same samples. Our findings reveal distinct clonal responses within TNBC tumors exposed to platinum. Clones with high drug fitness undergo clonal sweeps and show subtle transcriptional reversion, while those with weak fitness exhibit dynamic transcription upon drug withdrawal. Pathway analysis highlights convergence on epithelial-mesenchymal transition and cytokine signaling, associated with resistance. Furthermore, pseudotime analysis demonstrates hysteresis in transcriptional reversion, indicating generation of new intermediate transcriptional states upon platinum exposure.

Conclusions

Within a polyclonal tumor, clones with strong genotype-associated fitness under platinum remained fixed, minimizing transcriptional reversion upon drug withdrawal. Conversely, clones with weaker fitness display non-genomic transcriptional plasticity. This suggests CN-associated and CN-independent transcriptional states could both contribute to platinum resistance. The dominance of genomic or non-genomic mechanisms within polyclonal tumors has implications for drug sensitivity, restoration, and re-treatment strategies.
Leveraging neighborhood representations of single-cell data to achieve sensitive DE testing with miloDE
Authors: Missarova Alsu , Dann Emma , Rosen Leah , Satija Rahul , Marioni John
Published: July 2024

Single-cell RNA-sequencing enables testing for differential expression (DE) between conditions at a cell type level. While powerful, one of the limitations of such approaches is that the sensitivity of DE testing is dictated by the sensitivity of clustering, which is often suboptimal. To overcome this, we present miloDE—a cluster-free framework for DE testing (available as an open-source R package). We illustrate the performance of miloDE on both simulated and real data. Using miloDE, we identify a transient hemogenic endothelia-like state in mouse embryos lacking Tal1 and detect distinct programs during macrophage activation in idiopathic pulmonary fibrosis.
Joint effect of atrial fibrillation and obesity on mortality in critically ill patients
Authors: Zhang Hong-Da , Ding Lei , Mi Li-Jie , Zhang Ai-Kai , Liu Yuan-Dong , Peng Fu-Hua , Yan Xin-Xin , Shen Yu-Jing , Tang Min
Published: July 2024

Background

The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population.

Methods

Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods.

Results

The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p < 0.001), while obesity was linked to a 13.9% reduction in mortality risk (p < 0.001). The protective effect of obesity on mortality was similar in patients with (HR = 0.85) and without AF (HR = 0.86). AF led to a slightly higher risk of mortality in patients without obesity (HR = 1.16) compared to those with obesity (HR = 1.13). Kaplan-Meier survival curves highlighted that non-obese patients with AF had the lowest survival rate, whereas the highest survival was observed in obese patients without AF.

Conclusions

AF significantly increased 1-year mortality risk in critically ill patients, whereas obesity was associated with a decreased mortality risk. The most adverse survival outcomes were identified in non-obese patients with AF.
Exosomes repairment for sciatic nerve injury: a cell-free therapy
Authors: Xin Guang-Da , Liu Xue-Yan , Fan Xiao-Di , Zhao Guan-Jie
Published: July 2024

Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient’s quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.
Exploring the role of plant hydraulics in canopy fuel moisture content: insights from an experimental drought study on Pinus halepensis Mill. and Quercus ilex L.
Authors: Cakpo Coffi Belmys , Ruffault Julien , Dupuy Jean-Luc , Pimont François , Doussan Claude , Moreno Myriam , Jean Nathan , Jean Frederic , Burlett Regis , Delzon Sylvain , Trueba Santiago , Torres-Ruiz José M. , Cochard Hervé , Martin-StPaul Nicolas
Published: July 2024

Key Message

Understanding the impact of extreme drought on the canopy fuel moisture content (CFMC) is crucial to anticipate the effects of climate change on wildfires. Our study demonstrates that foliage mortality, caused by leaf embolism, can substantially diminish CFMC during drought on Pinus halepensis Mill. and Quercus ilex L. It emphasizes the importance of considering plant hydraulics to improve wildfire predictions.

Context

Canopy fuel moisture content (CFMC), which represents the water-to-dry mass ratio in leaves and fine twigs within the canopy, is a major factor of fire danger across ecosystems worldwide. CFMC results from the fuel moisture content of living foliage (live fuel moisture content, LFMC) and dead foliage (dead fuel moisture content, DFMC) weighted by the proportion of foliage mortality in the canopy (αDead). Understanding how LFMC, αDead, and ultimately CFMC are affected during extreme drought is essential for effective wildfire planning.

Aims

We aimed to understand how plant hydraulics affect CFMC for different levels of soil water deficit, examining its influence on both LFMC and αDead.

Methods

We conducted a drought experiment on seedlings of two Mediterranean species: Aleppo pine (Pinus halepensis Mill.) and Holm oak (Quercus ilex L.). Throughout the drought experiment and after rewatering, we monitored CFMC, LFMC, and αDead along with other ecophysiological variables.

Results

LFMC exhibited a significant decrease during drought, and as leaf water potentials reached low levels, αDead increased in both species, thereby reducing CFMC. Distinct water use strategies resulted in species-specific variations in dehydration dynamics.

Conclusion

Our findings demonstrate that as drought conditions intensify, foliage mortality might become a critical physiological factor driving the decline in CFMC.
Steady-state pharmacokinetics of lamivudine in end-stage kidney failure persons with detectable and undetectable HIV-1 RNA in peritoneal dialysis effluent
Authors: Mooko Teboho , Bisiwe Feziwe Busiswa , Mondleki Enkosi , Morobadi Molefi Daniel , Chikobvu Perpetual , Nyaga Martin Munene , Bala Asis , Goedhals Dominique , Mofokeng Thabiso Rafaki Petrus , Kemp Gabre , Ndlovu Kwazi Celani Zwakele
Published: July 2024

Background

Renally adjusted lamivudine dosages are effective. However, some of the kidney failure patients managed with lamivudine-containing regimens are failing to suppress HIV in peritoneal dialysis (CAPD) effluent. The steady-state lamivudine pharmacokinetics among these patients was evaluated.

Methods

This overnight open-label pharmacokinetic study enrolled participants living with HIV and managed with CAPD. Lamivudine levels in blood serum and CAPD effluent samples were quantified using liquid chromatography coupled with a mass spectrometer. Pharmacokinetic measures were obtained through non-compartmental analysis.

Results

Twenty-eight participants were recruited with a median antiretroviral (ARV) drug duration of 8 (IQR,4.5–10.5) years and a CAPD duration of 13.3 (IQR,3.3–31.9) months. 14.3% (4/28) had detectable unsuppressed HIV-1 viral load in CAPD effluents. The majority (78,6%,22/28) of participants received a 50 mg dose, while 10.7% (3/28), and another 10.7% (3/28) received 75 mg and 300 mg dosages, respectively. Among those treated with 75 and 300 mg, 66.7% (2/3) and 33.3% (1/3) had detectable HIV-VL in CAPD, respectively. The peritoneal membrane characteristics and CAPD system strengths were variable across the entire study population. Lamivudine exposure was increased in blood serum (50 mg-AUC0-24 h, 651.3 ng/mL; 75 mg-AUC0-24 h, 677.84 ng/mL; 300 mg-AUC0-24 h, 3135.89 ng/mL) compared to CAPD effluents (50 mg-AUC0-24 h, 384.91 ng/mL; 75 mg-AUC0-24 h, 383.24 ng/mL; 300 mg-AUC0-24 h, 2001.60 ng/mL) among the entire study population. The Cmax (50 mg, 41.5 ng/mL; 75 mg, 53.2 ng/mL; 300 mg, 199.1 ng/mL) and Cmin (50 mg, 17.8 ng/mL; 75 mg, 16.4 ng/mL; 300 mg, 76.4 ng/mL) measured in serum were within the therapeutic levels.

Conclusions

Steady-state lamivudine pharmacokinetic measures were variable among the entire study population. However, the total lamivudine exposure was within the therapeutic levels.
Carbapenem-resistant Acinetobacter baumannii infections among diabetic and non-diabetic patients and possible effective combination treatments
Authors: Ghareeb Aya M. , Raafat Marwa M. , Bazan Naglaa S. , Samir Reham
Published: July 2024

Background

Carbapenems are one of the most noteworthy choices for treating multidrug-resistant Acinetobacter baumannii (A. baumannii). Currently, carbapenem-resistant A. baumannii (CRAB) represents a healthcare problem worldwide, particularly among diabetic patients who are more susceptible to microbial infections. The aim of this study was to investigate the differences in antibiotic susceptibility profiles, the abundance of carbapenem resistance genes across A. baumannii-infected diabetic and non-diabetic patients, and the antimicrobial activity of different antibiotic combinations on highly resistant isolates.

Methods

Data of 99 A. baumannii-infected patients were collected during the period from 2018 to 2022 and categorized according to patients’ diabetes status into either diabetic or non-diabetic group. A total of 45 A. baumannii isolates were collected during 2021 and 2022 from the main hospital laboratory to be reidentified and genetically confirmed. Antibiotic susceptibility, including carbapenems, was determined using disc agar diffusion and broth microdilution methods. The isolates were screened for OXA-23, GES, VIM, and NDM carbapenem-resistant genes. Five antibiotic combinations were assessed using the double-disk synergy and checkerboard methods.

Results

The findings of the current study revealed that multidrug resistance increased gradually, from 56% in 2018 to 95.6% in 2022. Moreover, CRAB increased among diabetics and non-diabetics. Resistance rates of imipenem, meropenem, and doripenem reached 68.8%, 61.8%, and 47.4% in diabetics and 97.9%, 83.3%, and 50% in non-diabetics, respectively. The VIM gene was the most prevalent gene with prevalence rates of 100% and 96.15% in diabetics and non-diabetics, respectively. Moreover, all A. baumannii isolates carried at least two of the selected carbapenem-resistant genes. Across the different used combinations, only the tigecycline-meropenem combination showed synergistic activity in 50% of diabetic and 66.7% of non-diabetic isolates.

Conclusions

An increased carbapenem resistance was observed among A. baumannii-infected individuals, both diabetic and non-diabetic. The MEM/TCG combination was the only one that showed synergistic or additive effects against highly resistant isolates making it a viable alternative treatment option.
An automated optimized design of practical post-tensioned slabs
Authors: Farid Ahmed Fady , Kamal Abdulrahman , Rashed Youssef F.
Published: July 2024

In this paper, an efficient methodology that could be implemented within any analysis software is developed to automate the design process of post-tensioned slabs. Optimization techniques are used to compute the necessary number of strands. The present methodology is based on computing an innovative influence matrix that contains the effect of each strand on stresses at a set of control points (points of peak stresses). This matrix will be used in the optimization avoiding reanalysis in each optimization iteration. The sum of the squares of the difference between the allowable stress and the computed stresses at all control points is considered an objective function. The optimization is then carried out under the constraints that the stresses at each control point should not exceed the allowable limit and to ensure that the number of strands is an integer value. Alternatively, the proposed methodology could be used as a value-engineering tool. Practical examples are presented to demonstrate the efficiency of the developed methodology.
Stimulant medication and suicide mortality in attention-deficit hyperactivity disorder
Authors: Rice Korie M. , Peltzman Talya , Gottlieb Daniel , Shiner Brian , Watts Bradley Vincent
Published: July 2024

Patients diagnosed with attention-deficit hyperactivity disorder (ADHD) are at an elevated risk for suicide. No prior work has assessed the association between stimulant prescriptions and death by suicide in this population. This retrospective cohort study included Department of Veterans Affairs patients with an active ADHD diagnosis that received stimulant medications between 2016 and 2019. We found that months with active stimulant medication prescription was associated with decreased risk of suicide mortality compared with months without stimulant medication (odds ratio 0.57, 95% CI 0.36–0.88). Our results suggest that prescribing stimulant medications for patients diagnosed with ADHD is associated with decreased risk of suicide mortality.
Schrödinger evolution of a scalar field in Riemannian and pseudo-Riemannian expanding metrics
Authors: Haba Z.
Published: July 2024

We study the quantum field theory (QFT) of a scalar field in the Schrödinger picture in the functional formulation. We derive a formula for the evolution kernel in a flat expanding metric. We discuss a transition between Riemannian and pseudo-Riemannian metrics

(signature inversion). We express the real time Schrödinger evolution by the Brownian motion. We discuss the Feynman integral for a scalar field in a radiation background. We show that the unitary Schrödinger evolution for positive time can go over for negative time into a dissipative evolution as a consequence of the imaginary value of

. The time evolution remains unitary if

in the Hamiltonian is replaced by

.
NFATc1 Is Required for Vitamin D- and Phosphate-Mediated Regulation of Osteocyte Lacuno-Canalicular Remodeling
Authors: Jagga Supriya , Hughes Ashleigh , Manoochehri Arash Niusha , Sorsby Melissa , Brooks Daniel J , Divieti Pajevic Paola , Liu Eva S
Published: July 2024

Osteocytes are embedded in lacunae and connected by canaliculi (lacuno-canalicular network, LCN). Bones from mice with X-linked hypophosphatemia (Hyp), which have impaired production of 1,25 dihydroxyvitamin D (1,25D) and hypophosphatemia, have abnormal LCN structure that is improved by treatment with 1,25D or an anti-FGF23 targeting antibody, supporting roles for 1,25D and phosphate in regulating LCN remodeling. Bones from mice lacking the vitamin D receptor (VDR) in osteocytes (Vdrf/f;Dmp1Cre+) and mice lacking the sodium phosphate transporter 2a (Npt2aKO), which have low serum phosphate with high serum 1,25D, have impaired LCN organization, demonstrating that osteocyte-specific actions of 1,25D and hypophosphatemia regulate LCN remodeling. In osteoclasts, nuclear factor of activated T cells cytoplasmic 1 (NFATc1) is critical for stimulating bone resorption. Since osteocytes also resorb matrix, we hypothesize that NFATc1 plays a role in 1,25D and phosphate-mediated LCN remodeling. Consistent with this, 1,25D and phosphate suppress Nfatc1 mRNA expression in IDG-SW3 osteocytes, and knockdown of Nfatc1 expression in IDG-SW3 cells blocks 1,25D- and phosphate-mediated suppression of matrix resorption gene expression and 1,25D- and phosphate-mediated suppression of RANKL-induced acidification of the osteocyte microenvironment. To determine the role of NFATc1 in 1,25D- and phosphate-mediated LCN remodeling in vivo, histomorphometric analyses of tibiae from mice lacking osteocyte-specific Nfatc1 in Vdrf/f;Dmp1Cre+ and Npt2aKO mice were performed, demonstrating that bones from these mice have decreased lacunar size and expression of matrix resorption genes, and improved canalicular structure compared to Vdrf/f;Dmp1Cre+ and Npt2aKO control. This study demonstrates that NFATc1 is necessary for 1,25D- and phosphate-mediated regulation of LCN remodeling.
Point-of-Care Ultrasound for Gastric Volume Measurement in a Pediatric Patient—Look Beyond the Antrum: A Case Report
Authors: Narayanasamy Suryakumar , Weethee Joseph B. , Rao Deepika S. , Mecoli Marc D.
Published: July 2024

Gastric ultrasound estimates stomach contents in perioperative patients. A 10-year-old boy with abdominal rhabdomyosarcoma, who received abdominal radiation, developed gastroparesis and was scheduled for endoscopic gastrointestinal pyloric dilation. Point-of-care gastric ultrasound revealed gastric antral cross-sectional area of 6.5 cm2 (estimated gastric content ~30 mL). However, dynamic right-to-left ultrasound revealed more hypoechoic material in the fundus of the stomach. On induction ~125 mL of stomach contents was suctioned. Antral measurements may not accurately predict the stomach contents in the setting of a stiff/fixed antrum. Scanning from antrum to fundus determined contents more accurately, especially with a prior history of abdominal radiation.
Ranking Age-at-Death Distributions Using Dominance: Robust Evaluation of United States Mortality Trends, 2006–2021
Authors: Issa Jawa , Van Ourti Tom , van Baal Pieter , O'Donnell Owen
Published: July 2024

Diverging mortality trends at different ages motivate the monitoring of lifespan inequality alongside life expectancy. Conclusions are ambiguous when life expectancy and lifespan inequality move in the same direction or when inequality measures display inconsistent trends. We propose using nonparametric dominance analysis to obtain a robust ranking of age-at-death distributions. Application to U.S. period life tables for 2006–2021 reveals that, until 2014, more recent years generally dominate earlier years, implying improvement if longer lifespans that are less unequally distributed are considered better. Improvements were more pronounced for non-Hispanic Black and Hispanic individuals than for non-Hispanic White individuals. Since 2014, for all subpopulations—particularly Hispanics—earlier years often dominate more recent years, indicating worsening age-at-death distributions if shorter and more unequal lifespans are considered worse. Dramatic deterioration of the distributions in 2020–2021 during the COVID-19 pandemic is most evident for Hispanic individuals.
Stable germline transgenesis using the Minos Tc1/mariner element in the sea urchin Lytechinus pictus
Authors: Jackson Elliot W. , Romero Emilio , Kling Svenja , Lee Yoon , Tjeerdema Evan , Hamdoun Amro
Published: July 2024

Stable transgenesis is a transformative tool in model organism biology. Although the sea urchin is one of the oldest animal models in cell and developmental biology, studies in this animal have largely relied on transient manipulation of wild animals, without a strategy for stable transgenesis. Here, we build on recent progress to develop a more genetically tractable sea urchin species, Lytechinus pictus, and establish a robust transgene integration method. Three commonly used transposons (Minos, Tol2 and piggyBac) were tested for non-autonomous transposition, using plasmids containing a polyubiquitin promoter upstream of a H2B-mCerulean nuclear marker. Minos was the only transposable element that resulted in significant expression beyond metamorphosis. F0 animals were raised to sexual maturity, and spawned to determine germline integration and transgene inheritance frequency, and to characterize expression patterns of the transgene in F1 progeny. The results demonstrate transgene transmission through the germline, the first example of a germline transgenic sea urchin and, indeed, of any echinoderm. This milestone paves the way for the generation of diverse transgenic resources that will dramatically enhance the utility, reproducibility and efficiency of sea urchin research.
Μεταρρύθμιση του Αναλυτικού Προγράμματος Φυσικών Επιστημών από τη σκοπιά των Εκπαιδευτικών
Authors: Παπαδάκης Πέτρος , Σταύρου Δημήτρης
Published: July 2024

Είναι πλέον ευρέως αποδεκτό πως η σύγκλιση ανάμεσα στο περιεχόμενο μιας εκπαιδευτικής μεταρρύθμισης και τις απόψεις των εκπαιδευτικών, αποτελεί παράγοντα που μπορεί να συμβάλει στην επιτυχία της. Αυτό συνεπάγεται πως η κατανόηση του τρόπου με τον οποίο οι εκπαιδευτικοί αντιλαμβάνονται το αναλυτικό πρόγραμμα και τις σχετικές με αυτό μεταρρυθμίσεις, αποτελεί καθοριστικό στοιχείο για κάθε προσπάθεια βελτίωσης της εκπαίδευσης. Σε αυτή την εργασία, διερευνούμε τις απόψεις των εκπαιδευτικών φυσικών επιστημών δευτεροβάθμιας εκπαίδευσης σε σχέση με τα βασικά χαρακτηριστικά που οφείλει να έχει μια μεταρρύθμιση του αναλυτικού προγράμματος αλλά και τους παράγοντες που διαμορφώνουν την άποψή τους σε σχέση με μια τέτοια μεταρρύθμιση. Το δείγμα αποτέλεσαν 152 εκπαιδευτικοί, οι οποίοι απάντησαν σε ερωτηματολόγιο που συντάξαμε για τις ανάγκες της παρούσας έρευνας.
Evaluation of a safety-engineered peripherally inserted intravenous catheter with multiple access blood control: clinician acceptability and ease of use
Authors: Yeh Jesson , Valencia Diana , Curtin Christopher R. , Ballek Susan , Marshall-Hudson Allyson , Tuley Michael , Karpf Angela
Published: July 2024

Aim:

Acceptability of a new safety-engineered peripherally inserted intravenous catheter (PIVC) with multiple access blood control (MBC) was evaluated in this observational study by experienced volunteer clinicians on healthy volunteers.

Methods:

Clinicians and healthy volunteers were recruited for this study. Observers documented study procedures, including if there was any blood leakage from the catheter hub at various times during hub connections and disconnections and how many attempts it took a clinician to get a successful stick. Clinicians responded to yes-or-no and Likert-scale questionnaires describing their experiences with PIVC with MBC after each procedure. Questionnaire data were summarized by frequency and percent of responses; analyses were conducted using binomial statistics.

Results:

Overall, clinicians considered PIVC with MBC to be acceptable (93.6% agreement). Clinicians were able to easily remove the catheter protective cap, insert the catheter, visualize primary and secondary flashbacks, easily remove the needle from the catheter hub and determine if the safety clip was activated after withdrawing the needle. In addition, they were able to connect or disconnect and flush extension sets. Clinicians did not have to change their insertion technique, found the catheter easy to insert, and believed the catheter would protect them from blood exposure during insertion of the catheter and subsequent hub accesses (agreement ranged from 82.3% to 98.9%).

Conclusions:

No blood leakage was observed from the catheter hub at any time during the procedures. Overall, clinicians found the new PIVC with MBC to be acceptable, easy to use, and functioned properly.

HIGHLIGHTS

Acceptability, usability, and ease of use of a new safety-engineered PIVC with MBC was evaluated. PIVC with MBC was >93% acceptable: prevented blood exposure after multiple insertions/removals. Most clinicians (96%) achieved first stick success when using their product. PIVC with MBC was easy to use, worked properly and allowed clinicians to keep their PIVC technique.
Effectiveness of Structural Sediment Perimeter Barriers: Literature Review and Suggestions for Future Research
Authors: Zhang Yufan , Bhattarai Rabin , Flanagan Dennis C. , Privette Charles V.
Published: July 2024

Highlights

Need a unified test standard to evaluate the effectiveness of a sediment perimeter barrier (SPB).

Water sampling location affects the evaluation of a SPB in terms of water quality.

Explore more approaches with computational models to simulate the effectiveness of SPBs.

Over 80% of studies were done in the southeast region of the U.S., emphasizing more research with diverse geographical climate conditions.

Abstract. A sediment perimeter barrier is a common practice along the perimeter of construction sites to prevent sediment from being washed over all the way to the nearby storm drains or directly into water bodies. It is important to apply barriers during construction since the grading and demolition do not allow the application of other ground surface protection, such as erosion control blankets. To better understand the mechanism, this paper conducted a comprehensive review of the effectiveness of structural sediment perimeter barriers (SPBs) in preventing sediment pollution. The study systematically analyzed the experimental design and results of previous research studies, including their strengths and limitations. The findings suggest that while SPBs have shown promise in reducing sediment pollution, their effectiveness varies depending on factors such as experimental design, installation, and sampling approach. Worse still, the criteria to evaluate the SPBs also differed across different studies. From the reviewed studies, we identified that there is a need to develop a unified test standard, especially on evaluation criteria and water sampling protocol. Additionally, there is a need for more studies to be conducted in various geographical and climatic conditions to assess the performance of SPBs. Although some models (WEPP and VFSMOD) have been proven to be effective in predicting the effectiveness of non-structural SPBs (vegetative filter strips), exploring the feasibility of these existing models in simulating structural SPBs to be subjected to sediment-laden water is recommended. Other software or methods used in the area of computational fluid dynamics, such as HYDRUS-3D, ANASYS, EDEM, and finite volume methods (FVM), could also be introduced in this field. Keywords: Compost log, Filter sock, Perimeter control, Sediment control, Silt fence.
Peeking into Closets: A Review of Danielle Bobker’s The Closet: The Eighteenth-Century Architecture of Intimacy
Authors: Sutton-Bennett Karenza
Published: July 2024

Abstract: Danielle Bobker takes readers on a fascinating journey through the world of closets in the eighteenth century. Each chapter examines a different type of closet, whether it be a closet room, freestanding closet, water closet, moving closet, or textual closet.
Controlled dispersive waves emission via swallowtail-type catastrophe pulses
Authors: Zhang Xiang , Jing Liqing , Gao Yanxia , Fan Dianyuan , Zhang Lifu
Published: July 2024

The dispersive waves (DWs) emission has emerged as an efficient way to extend the spectral range of a light source. However, the applications of the DWs are limited because of its narrowband and low power. It is crucial to find novel ways to manipulate the DWs radiation. We investigate a kind of catastrophe pulses, called swallowtail pulses, which can radiate DWs with broadband and high power. By exploiting the dependence of the temporal and spectral structure of swallowtail pulses on the initial control parameter within the catastrophe integral, we can effectively manipulate the emission of DWs in terms of resonant frequency and conversion efficiency. Furthermore, we observe that the swallowtail pulses can shed two solitons, and that both of them radiate DWs with different frequencies. In comparison to fundamental solitons, the minimum value of third-order dispersion required for the onset of DWs emission becomes significantly smaller for that of swallowtail pulses. The results of this study clearly reveal the impact of the inherent behaviors of swallowtail pulses on the DWs emission, which should be relevant for applications requiring broadband light sources and optical frequency combs based on the mechanism of DWs emission.
Enhanced mutual information neural estimators for optical fiber communication
Authors: Niu Zekun , Dai Chenhao , Yang Hang , Zeng Chuyan , He Zhixue , Hu Weisheng , Yi Lilin
Published: July 2024

The accurate estimation of mutual information (MI) plays a vital role in understanding channel capacity and optimizing the performance of optical communications. While MI computations for the additive white Gaussian noise (AWGN) channel are well-established, they fall short when dealing with the challenges posed by nonlinear optical fiber channels due to an unknown channel model. For the first time, to our knowledge, this Letter introduces a mutual information neural estimator (MINE) for MI estimation in optical fiber communications. We propose an enhanced MINE (E-MINE), achieved by enlarging the training batch size to improve estimation accuracy and stability. Our findings reveal that the E-MINE achieves highly accurate estimations in the AWGN channel and maintains strong consistency with symbol-by-symbol MI estimations, comparable to Monte Carlo (MC) methods based on a Gaussian distribution in long-haul optical fiber channels. Furthermore, with multi-symbol estimation, the E-MINE yields a 0.16 bits/4D-symbol improvement in our experiments. We anticipate that our findings will drive further research in the field, opening new possibilities for enhancing communication systems design and performance using deep learning techniques.
Focusing membrane metamirrors for integrated cavity optomechanics
Authors: Agrawal A. R. , Manley J. , Allepuz-Requena D. , Wilson D. J.
Published: July 2024

Membrane-based cavity optomechanical systems have been widely
successful; however, their chip-scale integration remains a
significant challenge. Here we present a solution based on metasurface
design. Specifically, by non-periodic photonic crystal patterning of a Si3N4 membrane, we realize a suspended
metamirror with a finite focal length, enabling formation of a stable
optical cavity with a plane end-mirror. We present simulation,
fabrication, and characterization of the metamirror using both
free-space and cavity-based measurements, demonstrating reflectivities
as high as 99% and cavity finesse as high as 600. The mirror radius of
curvature (∼30cm) is inferred from the cavity mode
spectrum. In combination with phononic engineering, focusing membrane
mirrors offer a route towards high-cooperativity, vertically
integrated cavity optomechanical systems with applications ranging
from precision force sensing to hybrid quantum transduction.
Behavioral adjustment of C. elegans to mechanosensory loss requires intact mechanosensory neurons
Authors: Staum Michal , Abraham Ayelet-Chen , Arbid Reema , Birari Varun Sanjay , Dominitz Matanel , Rabinowitch Ithai
Published: July 2024

Sensory neurons specialize in detecting and signaling the presence of diverse environmental stimuli. Neuronal injury or disease may undermine such signaling, diminishing the availability of crucial information. Can animals distinguish between a stimulus not being present and the inability to sense that stimulus in the first place? To address this question, we studied Caenorhabditis elegans nematode worms that lack gentle body touch sensation due to genetic mechanoreceptor dysfunction. We previously showed that worms can compensate for the loss of touch by enhancing their sense of smell, via an FLP-20 neuropeptide pathway. Here, we find that touch-deficient worms exhibit, in addition to sensory compensation, also cautious-like behavior, as if preemptively avoiding potential undetectable hazards. Intriguingly, these behavioral adjustments are abolished when the touch neurons are removed, suggesting that touch neurons are required for signaling the unavailability of touch information, in addition to their conventional role of signaling touch stimulation. Furthermore, we found that the ASE taste neurons, which similarly to the touch neurons, express the FLP-20 neuropeptide, exhibit altered FLP-20 expression levels in a touch-dependent manner, thus cooperating with the touch circuit. These results imply a novel form of neuronal signaling that enables C. elegans to distinguish between lack of touch stimulation and loss of touch sensation, producing adaptive behavioral adjustments that could overcome the inability to detect potential threats.