bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in hospital-supported substance use services across US nonprofit hospitals, 2015-2021
Authors: Cronin Cory E , Franz Berkeley , Lindenfeld Zoe , Yuanhong Lai Alden , Pagán José A , Chang Ji
Published: October 2024

Substance use remains a timely and important community need to understand and address. Nonprofit hospitals are in a unique position to identify needs and develop programs in response to substance use challenges in their communities. To better understand how nonprofit hospitals do this, we collected data from community health needs assessments and their corresponding implementation strategy (IS) to address these needs for a 20% random sample of hospitals in each state of the United States over 2 periods (2015-2018 and 2019-2021). The sample of nonprofit hospitals came from the American Hospital Association's (AHA) Annual Survey Database. Community health needs assessment and IS documents were coded for the inclusion of substance use programs using a systematic protocol and analyzed quantitatively. We found that the percentage of nonprofit hospitals in our sample with at least 1 substance use program increased from 66.5% in 2015-2018 to 73.6% in 2019-2021. Of the types of programs analyzed, harm reduction approaches saw the greatest increase in implementation in the time period studied, while primary care approaches decreased. This indicates that hospitals are continuing or even increasing their responses to community needs regarding substance use, but there is evidence that their approaches in doing so are shifting over time.
Midlife health in Britain and the United States: a comparison of two nationally representative cohorts
Authors: Bridger Staatz Charis , Gutin Iliya , Tilstra Andrea , Gimeno Laura , Moltrecht Bettina , Moreno-Agostino Dario , Moulton Vanessa , Narayanan Martina K , Dowd Jennifer B , Gaydosh Lauren , Ploubidis George B
Published: October 2024

Background

Older adults in the USA have worse health and wider socioeconomic inequalities in health compared with those in Britain. Less is known about how health in the two countries compares in mid-life, a time of emerging health decline, including inequalities in health.

Methods

We compare measures of current regular smoking status, obesity, self-rated health, cholesterol, blood pressure and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N = 9665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the USA (N = 12 300), when cohort members were aged 34–46 and 33–43, respectively. We test whether associations vary by early- and mid-life socioeconomic position.

Results

US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health and current regular smoking was worse in Britain. We found smaller socioeconomic inequalities in mid-life health in Britain compared with the USA. For some outcomes (e.g. smoking), the most socioeconomically advantaged group in the USA was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain.

Conclusions

US adults have worse cardiometabolic health than British counterparts, even in early mid-life. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems or other environmental risk factors.
Using disruptive innovation to design endoscopic ligators for resource-challenged health settings
Authors: Gardner Jack T , Dusabejambo Vincent , Bensen Steve P
Published: October 2024

Background

Commercial single-use endoscopic multiband ligators, used for esophageal variceal band ligation (EVL), are prohibitively expensive. To enable greater access to EVL, we used disruptive innovation to develop a novel endoscopic multiband ligator.

Methods

We designed and tested a prototype handle ‘ENDOhandle’ using computer-aided design modeling and exported a cap, trigger cord and latex to form a functional banding unit.

Results

The cost of the banding unit was US$4.80 compared with several hundred US dollars for commercially available devices in the USA.

Conclusions

Disruptive innovation technology developed an inexpensive ligator for resource-challenged health settings.
Leveraging genomic information to predict environmental preferences of bacteria
Authors: Ramoneda Josep , Hoffert Michael , Stallard-Olivera Elias , Casamayor Emilio O , Fierer Noah
Published: October 2024

Genomic information is now available for a broad diversity of bacteria, including uncultivated taxa. However, we have corresponding knowledge on environmental preferences (i.e. bacterial growth responses across gradients in oxygen, pH, temperature, salinity, and other environmental conditions) for a relatively narrow swath of bacterial diversity. These limits to our understanding of bacterial ecologies constrain our ability to predict how assemblages will shift in response to global change factors, design effective probiotics, or guide cultivation efforts. We need innovative approaches that take advantage of expanding genome databases to accurately infer the environmental preferences of bacteria and validate the accuracy of these inferences. By doing so, we can broaden our quantitative understanding of the environmental preferences of the majority of bacterial taxa that remain uncharacterized. With this perspective, we highlight why it is important to infer environmental preferences from genomic information and discuss the range of potential strategies for doing so. In particular, we highlight concrete examples of how both cultivation-independent and cultivation-dependent approaches can be integrated with genomic data to develop predictive models. We also emphasize the limitations and pitfalls of these approaches and the specific knowledge gaps that need to be addressed to successfully expand our understanding of the environmental preferences of bacteria.
Simple Porifera holobiont reveals complex interactions between the host, an archaeon, a bacterium, and a phage
Authors: Garritano Alessandro N , Zhang Zhelun , Jia Yunke , Allen Michelle A , Hill Lilian J , Kuzhiumparambil Unnikrishnan , Hinkley Cora , Raina Jean-Baptiste , Peixoto Raquel S , Thomas Torsten
Published: October 2024

The basal metazoan phylum Porifera (sponges) is increasingly used as a model to investigate ecological and evolutionary features of microbe–animal symbioses. However, sponges often host complex microbiomes, which has hampered our understanding of their interactions with their microbial symbionts. Here, we describe the discovery and characterization of the simplest sponge holobiont reported to date, consisting of the deep-sea glass sponge Aphrocallistes beatrix and two newly-described microbial symbionts: an autotrophic ammonia-oxidizing archaeon and a bacterial heterotroph. Omics analyses and metabolic modeling revealed the dependency of the ammonia-oxidizing archaea on sponge-derived ammonia to drive primary production, which in turn supports the bacterium’s growth by providing the dicarboxylate fumarate. Furthermore, virus-mediated archaeal lysis appears crucial to overcome the bacterium’s vitamin B12 auxotrophy. These findings reveal that the exchanges of vitamin B12 and dicarboxylate may be evolutionarily conserved features of symbiosis as they can also be found in interactions between free-living marine bacteria, and between microbes and plants or diatoms.
Validation of Enzytec™ Liquid Citric Acid for Enzymatic Determination of Citric Acid in Selected Foods and Beverages: First Action 2024.02
Authors: Lacorn Markus , Hektor Thomas
Published: October 2024

Background

Due to its excellent acidifier, antioxidant, and preservative properties, citric acid is added to or is a constituent in a broad range of foods and beverages. Its measurement should be performed to assure the food quality specifications are met.

Objective

To validate the performance of the Enzytec™ Liquid Citric acid test kit for the determination in food and beverages such as wines, juices, and tomato products.

Methods

The kit contains two ready-to-use components, which makes handling very easy and suitable for automation. Citrate is cleaved into oxaloacetate and acetate by citrate lyase. Oxaloacetate reacts to L-malate by L-malate dehydrogenase and reduced nicotinamide adenine dinucleotide (NADH). Pyruvate, spontaneously formed from oxaloacetate, is converted by L-lactate dehydrogenase to L-lactate. The NADH consumed is equivalent to the amount of citric acid converted and is measured at a wavelength of 340 nm within 20 min.

Results

The test is specific to citric acid and shows no relevant interferences. Limit of detection and limit of quantification are 15 and 40 mg/L, respectively when using a test volume of 100 µL. The linear measurement range is from 40 to 1000 mg/L citric acid. Trueness was evaluated using materials from FAPAS, NIST, LGC, and two control wines from the German Wine Analysts. Matrix interference was evaluated by spiking tomato ketchup, tomato paste, orange juice, and carbonated beverages and resulted in recoveries around 100%. Intermediate precision is between 6.2 and 8.5% for matrixes with extraction and below 4% for matrixes measured directly. For automation, three applications with different test volumes and different measurement ranges were validated. Linearity is given from 8 mg/L up to 5 g/L (depending on the test volume).

Conclusions

The method is robust and accurate for manual and automated applications. The method was approved as an AOAC Official Method of Analysis℠.

Highlights

The ready-to-use components of the test kit have a shelf life of at least 24 months from the date of manufacture.
IPM messaging: who, what, how?—Insights from a survey of farmers and agronomists in Scotland
Authors: Creissen Henry E , Meador Elliot
Published: October 2024

Enhanced awareness and knowledge among arable (field crop) farmers and agronomists are pivotal for making informed integrated pest management (IPM) decisions. In this study, we had 3 primary objectives: (i) identifying the key factors influencing the adoption of IPM, (ii) gathering insights into the currently perceived pest threats, and (iii) identifying any necessary intervention tools or methods for modifying the flow of information. In 2021, a telephone survey involving 267 arable and arable/livestock farmers and 26 agronomists was conducted in Scotland. The survey was designed to gather information on the perceived invertebrate pest, disease, and weed threats, the extent of IPM implementation, and the sources of information consulted. Several factors influenced the uptake of IPM, including farm type, location, agronomist engagement, farmer’s age, education, and membership in schemes promoting IPM. Notably, there were disparities in perceptions of the most significant pest threats between arable farmers and agronomists. This points to a division of decision-making responsibilities and, consequently, varying information needs. Agronomists typically require technical information related to pesticide effectiveness and disease management, whereas arable farmers seek guidance on cultural approaches for managing weeds and invertebrate pests. Furthermore, preferences for information sources also differed, with agronomists showing a preference for social media as a source of IPM information, while farmers favored the farming press. Ultimately, a deeper understanding of IPM practices equips farmers to actively participate in IPM discussions with their agronomists. This enables the collaborative development of an effective IPM strategy and, in turn, increases the adoption of IPM practices.
Oviposition biology, behavior, and avocado cultivar preferences of Heilipus lauri Boheman (Coleoptera: Curculionidae)
Authors: Hoddle Mark S , Hoddle Christina D , Milosavljević Ivan , Estrada-Venegas Edith G , Equihua-Martínez Armando
Published: October 2024

Heilipus lauri is a specialist avocado seed feeding weevil native to parts of México and is an invasive pest in Colombia. This weevil is considered an incursion risk because possible unintended introductions into areas outside of its native range can result in establishment, which threatens avocado production in invaded regions. Despite being a well-recognized pest of avocados, relatively little is known about oviposition biology, behavior, and cultivar preferences of this weevil. Field studies in commercial Hass avocado orchards in México and laboratory studies in a quarantine facility in California (USA) indicated that H. lauri prefers to oviposit into middle and bottom thirds of fruit. In the laboratory, an average of 1.7 eggs (range 1–6 eggs) are laid over a 24-h period in oviposition chambers by individual females. Conspecifics add eggs to these clutches, with up to 17 eggs being recorded in 1 oviposition chamber. This finding suggests that H. lauri does not use an oviposition deterring pheromone. Female weevils readily oviposit in artificial holes representing mechanical wounds on fruit. In comparison to the commercially dominant Hass variety, fruit from Lamb Hass and G22, a native Guatemalan variety, and to a lesser extent Gem, may be less preferred for oviposition when females have a choice of fruit in which to oviposit. Videography studies indicated that H. lauri exhibits predominantly diurnal activity with respect to oviposition behaviors, feeding, and walking.
Urinary benzyl alcohol and hippuric acid in workers exposed to benzyl alcohol during paint-stripping work
Authors: Ishii Kenta , Takeuchi Akito , Shimada Masami , Momokawa Hiromi , Tashiro Tomiko , Yamada Ai , Arai Kumiko , Namera Akira , Yamamuro Kenji , Kato Koichi , Kawamoto Toshihiro , Endo Ginji
Published: October 2024

Objective: We aimed to develop a reliable gas chromatography–mass spectrometry (GC–MS) method for detecting urinary benzyl alcohol (BeOH) concentrations and assess the suitability of urinary BeOH as a biomarker for occupational BeOH exposure.

Methods: Thirteen male participants exposed to BeOH during paint-stripping work provided preshift and postshift urine samples, and their personal exposure concentrations were measured. Meanwhile, a control group of 10 nonexposed workers contributed urine samples. The newly developed GC–MS method met regulatory guidelines.

Results: The personal exposure concentrations of BeOH ranged from 8.4 to 45.2 mg/m3. Postshift urine samples from exposed participants showed significant BeOH and hippuric acid (HA) concentration increases compared with preshift samples (BeOH, post-/pre-shift geometric mean [GM] ratio = 7.5-7.8, P < .001; HA, post-/pre-shift GM ratio = 4.3-4.5, P < .001). These levels were considerably higher than those in postshift samples from the nonexposed control group (BeOH, exposed-/nonexposed-workers GM ratio = 14.8-19.0, P < .001; HA, exposed-/nonexposed-workers GM ratio = 12.1-15.3, P < .001), even after urine density correction.

Conclusions: Urinary BeOH and HA can serve as potential biomarkers of occupational exposure to BeOH. More specifically, BeOH might serve as a biomarker superior to HA because it is apparently less influenced by confounding factors such as dietary intake and genetic polymorphism of low-Km aldehyde dehydrogenase (ALDH2). The findings will improve workplace safety measures and protocols, assisting health care professionals in diagnosing and managing exposure-related health issues, thereby potentially reducing the risk of occupational exposure to BeOH.
Hydroxyurea reduces the levels of the fetal globin gene repressors ZBTB7A/LRF and BCL11A in erythroid cells in vitro
Authors: Martyn Gabriella E , Doerfler Phillip A , Yao Yu , Quinlan Kate G R , Weiss Mitchell J , Crossley Merlin
Published: October 2024

Objectives

Hydroxyurea (HU) is the most widely used therapy for adults and children with sickle cell disease (SCD). It is believed to act largely by inducing the transcription of fetal γ-globin genes to generate fetal hemoglobin (HbF), which inhibits the pathological polymerization of sickle hemoglobin (HbS). The mechanisms by which hydroxyurea elevates HbF are unclear. We explored the hypothesis that hydroxyurea induces HbF expression by inhibiting the expression of 2 γ-globin gene repressors, BCL11A and ZBTB7A (also known as LRF), which normally bind the γ-globin gene promoters to inhibit their expression after birth.

Methods

We treated immortalized murine erythroleukemia cells and normal human donor CD34+ hematopoietic stem and progenitor cell-derived erythroblasts with hydroxyurea and measured the effects on globin, BCL11A and ZBTB7A protein and mRNA expression.

Results

Treating murine erythroleukemia cells or human CD34+ hematopoietic stem and progenitor cell-derived erythroblasts with hydroxyurea reduced the protein levels of BCL11A and ZBTB7A compared to the vehicle-treated control. BCL11A mRNA levels were reduced in both cell types upon hydroxyurea treatment. However, ZBTB7A mRNA levels were only reduced in human CD34+ hematopoietic stem and progenitor cell-derived erythroblasts.

Conclusions

Hydroxyurea can act in erythroid cells to reduce the levels and activity of two direct fetal γ-globin transcriptional repressors with accompanying de-repression of the γ-globin genes and induction of HbF, which may explain the mechanism of action leading to amelioration of symptoms in SCD patients treated with this drug.
ALOG/LSHs: a novel class of transcription factors that regulate plant growth and development
Authors: Upadhyaya Gouranga , Sethi Vishmita , Modak Annayasa , Gangappa Sreeramaiah N
Published: October 2024

The ARABIDOPSIS LIGHT-DEPENDENT SHORT HYPOCOTYLS 1 and rice G1/LIGHT-DEPENDENT SHORT HYPOCOTYLS (ALOG/LSH) group proteins are highly conserved across plant lineages from moss to higher flowering plants, suggesting their crucial role in the evolution and adaptation of land plants. The role of ALOG/LSH proteins is highly conserved in various developmental responses, such as vegetative and reproductive developmental programs. Their role in meristem identity, cotyledon development, seedling photomorphogenesis, and leaf and shoot development has been relatively well established. Moreover, several key pieces of evidence suggest their role in inflorescence architecture and flower development, including male and female reproductive organs and flower colouration. Recent research has started to explore their role in stress response. Functionally, ALOG/LSH proteins have been demonstrated to act as transcriptional regulators and are considered a newly emerging class of transcription factors in plants that regulate diverse developmental and physiological processes. This review aims to stimulate discussion about their role in plant development and as transcription factors. It also seeks to further unravel the underlying molecular mechanism by which they regulate growth and development throughout the plant lineage.
AstroSat’s view of 4U 1735−44: spectral, temporal, and type I X-ray burst studies
Authors: Lavanya S , Thomas Neal Titus , Gudennavar S B , Bubbly S G
Published: October 2024

This study utilizes the simultaneous broad-band observations of 4U 1735−44 from AstroSat, offering enhanced spectral and temporal resolution, to investigate its spectral properties, temporal behaviour, and burst characteristics. Spectral, type I X-ray burst, and temporal analyses on 4U 1735−44 were performed using AstroSat/Soft X-ray Telescope and Large Area X-ray Proportional Counter (LAXPC) observations. The hardness–intensity diagram from LAXPC-20 showed a positive correlation between hardness and intensity, with a pattern resembling the banana branch typical of atoll sources. Spectral analysis carried out in the 0.7–20.0 keV energy range, using the model combination – $\tt {constant}$$\times$$\tt {tbabs}$ ($\tt {nthcomp}$$+$$\tt {diskbb}$$+$$\tt {bbodyrad}$), suggested a cool accretion disc truncated at a large distance from the neutron star in the system. Time-resolved spectral studies of two type I X-ray bursts detected from the source revealed evidence of photospheric radius expansion, allowing for an estimation of the source distance. Temporal analysis showed the presence of low-frequency quasi-periodic oscillation at $\sim$69 Hz (3.3$\sigma$ significance with more than 99 per cent confidence) and prominent noise features below 30 Hz.
An accurate equation for the gravitational bending of light by a static massive object
Authors: del Barco Oscar
Published: October 2024

An exact analytical expression for the bending angle of light due to a non-rotating massive object, considering the actual distances from source and observer to the gravitational mass, is derived. Our novel formula generalizes Darwin’s well-known equation for gravitational light bending, where both source and observer are placed at infinite distance from the lensing mass, and provides excellent results in comparison with the post-Newtonian (PPN) formalism up to first order. As a result, the discrepancy between our recent expression and the PPN approach is 6.6 mas for sun-grazing beams coming from planet Mercury, with significant differences up to 2 mas for distant starlight. Our findings suggest that these considerations should not be dismissed for both solar system objects and extragalactic sources, where non-negligible errors might be present in ultraprecise astrometry calculations.
Modulation of UPF1 catalytic activity upon interaction of SARS-CoV-2 Nucleocapsid protein with factors involved in nonsense mediated-mRNA decay
Authors: Mallick Megha , Boehm Volker , Xue Guangpu , Blackstone Mark , Gehring Niels H , Chakrabarti Sutapa
Published: October 2024

The RNA genome of the SARS-CoV-2 virus encodes for four structural proteins, 16 non-structural proteins and nine putative accessory factors. A high throughput analysis of interactions between human and SARS-CoV-2 proteins identified multiple interactions of the structural Nucleocapsid (N) protein with RNA processing factors. The N-protein, which is responsible for packaging of the viral genomic RNA was found to interact with two RNA helicases, UPF1 and MOV10 that are involved in nonsense-mediated mRNA decay (NMD). Using a combination of biochemical and biophysical methods, we investigated the interaction of the SARS-CoV-2 N-protein with NMD factors at a molecular level. Our studies led us to identify the core NMD factor, UPF2, as an interactor of N. The viral N-protein engages UPF2 in multipartite interactions and can negate the stimulatory effect of UPF2 on UPF1 catalytic activity. N also inhibits UPF1 ATPase and unwinding activities by competing in binding to the RNA substrate. We further investigate the functional implications of inhibition of UPF1 catalytic activity by N in mammalian cells. The interplay of SARS-CoV-2 N with human UPF1 and UPF2 does not affect decay of host cell NMD targets but might play a role in stabilizing the viral RNA genome.
Identification of phytoplankton isolates from the eastern Canadian waters using long-read sequencing
Authors: Mordret Solenn , MacKinnon Jenna , Behnke Joerg , O’Leary Stephen J B , Chénard Caroline
Published: October 2024

As important primary producers and key components of biogeochemical processes, phytoplankton communities are highly diverse and continually adapt to changes in the environment, impacting the entire marine ecosystem. Consequently, it remains important to isolate, culture and properly describe new phytoplankton strains to provide relevant model organisms for laboratory research and accurate reference sequences for identification. Here, 73 phytoplankton strains from the eastern Canadian waters were isolated and genetically characterized using a long rRNA fragment (~4000 bp) covering the 18S, ITS and 28S rRNA regions generated with long-read sequencing technology. While most strains (66%) were accurately identified using the partial 18S rRNA gene (~1200 bp—V4–V9), this study broadens the current 28S rRNA reference database by incorporating 41 distinct strains including 30 unique species. In addition, previously unpublished long-read reference sequences were generated for a few genera, including Picochlorum and Droopiella. Species that were previously poorly described in the eastern Canadian waters were also genetically characterized, including a Chaetoceros similis strain. Overall, this work expands the total number of long-read references, an essential resource for accurate identification of phytoplankton and environmental sequences, thereby advancing the taxonomic resolution that could lead to a better understanding of environmental microbial diversity.
Position-dependent roles of somatic cells in phototaxis of Volvox
Authors: Harada Keigo , Komasaka Yukariko , Yamada Keisuke , Iizuka Takumi , Otani Minato , Murayama Yoshihiro
Published: October 2024

A spherical green alga, Volvox, achieves phototaxis via a simple on/off switch of flagellar beating in response to changes in light intensity, without the need for complex signal transduction between cells. Moreover, the alga can change its susceptibility to light in order to adapt to its environment. To identify the mechanisms of susceptibility regulation, experiments were conducted at three different levels: population, individual, and cellular. The light intensity dependence of the average velocity at the population level and that of the change in flow speed obtained at the individual level were consistent, indicating that susceptibility regulation occurred in each Volvox colony. Furthermore, by measuring the probability of stopping flagellar beating when the light intensity was changed, susceptibility regulation was found to result from the properties of somatic cells as differential and adaptive photosensors. These photosensing properties deteriorated from the anterior to the posterior regions of the colony. Considering the mechanical motion of a Volvox colony, the position-dependent ability of somatic cells indicates that the anterior cells play the role of a rudder, whereas the posterior cells play the role of a rower. The position-dependent properties of somatic cells imply an early stage of cell differentiation that allows for an efficient response to changes in the circumstances.
Reprogramming with Atoh1, Gfi1, and Pou4f3 promotes hair cell regeneration in the adult organ of Corti
Authors: McGovern Melissa M , Ghosh Sumana , Dupuis Colleen , Walters Bradley J , Groves Andrew K
Published: October 2024

Cochlear hair cells can be killed by loud noises, ototoxic drugs, and natural aging. Once lost, mammalian hair cells do not naturally regenerate, leading to permanent hearing loss. Since the mammalian cochlea lacks any intrinsic ability to regenerate, genetic reprogramming of cochlear supporting cells that lie adjacent to hair cells is a potential option for hearing restoration therapies. We targeted cochlear supporting cells with three hair cell transcription factors: Atoh1, or Atoh1 + Gfi1, or Atoh1 + Gfi1 + Pou4f3 and found that 1- and 2-factor reprogramming is not sufficient to reprogram adult supporting cells into hair cells. However, activation of all three hair cell transcription factors reprogrammed some adult supporting cells into hair cell-like cells. We found that killing endogenous hair cells significantly improved the ability of supporting cells to be reprogrammed and regenerated numerous hair cell-like cells throughout the length of the cochlea. These regenerated hair cell-like cells expressed myosin VIIa and parvalbumin, as well as the mature outer hair cell protein prestin, were innervated, expressed proteins associated with ribbon synapses, and formed rudimentary stereociliary bundles. Finally, we demonstrate that supporting cells remained responsive to transcription factor reprogramming for at least 6 weeks after hair cell damage, suggesting that hair cell reprogramming may be effective in the chronically deafened cochlea.
Mapping uterine calcium dynamics during the ovulatory cycle in live mice
Authors: Combs David J , Moult Eric M , England Sarah K , Cohen Adam E
Published: October 2024

Uterine contraction patterns vary during the ovulatory cycle and throughout pregnancy, but prior measurements have produced limited and conflicting information on these patterns. We combined a virally delivered genetically encoded calcium reporter (GCaMP8m) and ultra-widefield imaging in live nonpregnant mice to characterize uterine calcium dynamics at organ scale throughout the estrous cycle. Prior to ovulation (proestrus and estrus), uterine excitations primarily initiated in a region near the oviduct, but after ovulation (metestrus and diestrus), excitations initiated at loci homogeneously distributed throughout the organ. The frequency of excitation events was lowest in proestrus and estrus, higher in metestrus, and highest in diestrus. These results establish a platform for mapping uterine activity and demonstrate that an anatomically localized trigger for uterine excitations depends on the estrous cycle phase.
Do stress hormones influence choice? A systematic review of pharmacological interventions on the HPA axis and/or SAM system
Authors: Sarmiento Luis Felipe , Ríos-Flórez Jorge Alexander , Rincón Uribe Fabio Alexis , Rodrigues Lima Rafael , Kalenscher Tobias , Gouveia Amauri , Nitsch Felix Jan
Published: October 2024

The hypothalamus–pituitary–adrenal axis (HPA axis) and the sympathetic–adrenal–medullary system (SAM system), two neuroendocrine systems associated with the stress response, have often been implicated to modulate decision-making in various domains. This systematic review summarizes the scientific evidence on the effects of pharmacological HPA axis and SAM system modulation on decision-making. We found 6375 references, of which 17 studies fulfilled our inclusion criteria. We quantified the risk of bias in our results with respect to missing outcome data, measurements, and selection of the reported results. The included studies administered hydrocortisone, fludrocortisone (HPA axis stimulants), yohimbine, reboxetine (SAM system stimulants), and/or propranolol (SAM system inhibitor). Integrating the evidence, we found that SAM system stimulation had no impact on risk aversion, loss aversion or intertemporal choice, while SAM system inhibition showed a tentative reduction in sensitivity to losses. HPA axis stimulation had no effect on loss aversion or reward anticipation but likely a time-dependent effect on decision under risk. Lastly, combined stimulation of both systems exhibited inconsistent results that could be explained by dose differences (loss aversion) and sex differences (risk aversion). Future research should address time-, dose-, and sex-dependencies of pharmacological effects on decision-making.
Role of bone marrow mesenchymal stem cell-derived exosomes in reducing neurotoxicity and depression-like behaviors induced by doxorubicin in rats
Authors: Abdel-Gawad Doaa R I , Khalil Fatma , Shehata Olfat , Ibrahim Marwa A , El-Samannoudy SalmaI , Mahdi Emad A , Shaban Nema S
Published: October 2024

Background

Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited nowadays due to its neurobiological side effects associated with depression. Bone marrow mesenchymal stem cells (BM-MSCs) derived exosomes are a promising regenerative therapy. In this study, we investigated the therapeutic potentiality of BM-MSCs derived exosomes against the neurotoxicity induced by DOX.

Methods

Twenty-four male albino rats were divided equally in to three groups as follow: group 1 (control), group 2 (rats injected intraperitoneally (i.p|) with DOX at a dose 2.5mg/Kg), and group 3 (rats injected with DOX and BM-MSCs derived exosomes i.p at a dose 1.5ml/Kg). During the experiment the behavior tests were noted, after three weeks rats were sacrificed, serum and brain samples were collected for biochemical, molecular and histopathological examinations.

Results

The results revealed that DOX causing impairment of the locomotor and increasing the anxiety like behavior of rats, marked neuropathological changes, significant elevation of MDA content and TNF-α concentration, reduction of phospholipase (PLD) and acetylcholinesterase (AChE) protein concentration in addition, there were up regulation of JNK, NF-κB and p38 genes and down regulation of Erk1.

Conclusion

Exosomal therapy improved the substantial neurotoxicity of DOX through modulating the markers involved in the neurotoxic signalling pathway of DOX that resulting in improving the pathological lesions and the animal behaviours.
“Exploring therapeutic potential and toxicological profiles of Cuscuta species: insights from pharmacological studies and an anti-cholinergic toxicity report.”
Authors: Bhandare Saurabh Dilip
Published: October 2024

This study examines the therapeutic potential and toxicological profiles of Cuscuta species based on recent pharmacological investigations: “a therapeutic potential vs. toxicological risks of Cuscuta species: a pharmacological-toxicology dilemma.” The study encompasses diverse research areas, including the mitigation of Bisphenol A (BPA)-induced ovarian damage using Cuscuta chinensis flavonoids (CCFs), acute and sub-acute toxicity assessments of Cuscuta chinensis Lam. water extract (CLW), and observations on Cuscuta campestris toxicity in horses. In addition, this scientific study discusses the interplant communication dynamics between soybean and the parasitic dodder (Cuscuta australis) under nutrient deficiency conditions. Key significant findings highlight the efficacy of CCFs in alleviating BPA-induced ovarian damage, the safety profile of CLW within specified doses, and clinical manifestations of C. campestris toxicity in horses. Moreover, insights into interplant communication mechanisms emphasise the significance of protein-mediated interactions in nutrient-deficient environments. The report illustrates the potential toxicity of Dodder in humans, and further research findings into its chemical composition and toxicological profiles reveal great data on its phytotoxicity. Greater awareness and understanding of the risks associated with consuming Dodder and other similar plant species are crucial for preventing plant intoxication and have been a significant major focus of the present toxicology study of Cuscuta species. Hence, by addressing these objectives, the scientific study aims to balance the therapeutic benefits of Cuscuta species with their potential toxicological risks, contributing to a more nuanced understanding of their role in pharmacology and toxicology. This dual focus is crucial for guiding future research and informing safe usage practices.
Di(2-ethylhexyl) phthalate exposure aggravates hypoxia/reoxygenation injury in cerebral endothelial cells by downregulating epithelial cadherin expression
Authors: Kim Jin Hee , Lee Jae Hoon , Nan Zhengyu , Choi Ja Woo , Song Jong Wook
Published: October 2024

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that has adverse health effects. Most phthalates exhibit reproductive toxicity and are associated with diseases such as cardiovascular disorders. However, the effect of DEHP exposure on acute hypoxia/reperfusion injury remains unknown. Therefore, we assessed whether hypoxia/reperfusion injury is aggravated by exposure to DEHP and investigated plausible underlying mechanisms, including oxidative stress and expression of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and endothelial junctional proteins. bEnd.3 cells were exposed to DEHP and subsequently subjected to oxygen–glucose deprivation (OGD). Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) proliferation assay. The effect of DEHP/OGD/reoxygenation (R) was evaluated by assessing the levels of NO, reactive oxygen species (ROS), and PGE2. The expression of COX-2, cleaved caspase-3, cleaved PARP, inducible nitric oxide synthase (iNOS), and the endothelial tight junction proteins claudin-5 and ZO-1 was evaluated using quantitative polymerase chain reaction and western blotting. OGD/R decreased cell viability, and DEHP exposure before OGD/R further aggravated cell viability. DEHP/OGD/R significantly increased NO, PGE2, and ROS production following OGD/R. In the DEHP/OGD/R group, iNOS, COX-2, cleaved caspase-3, and cleaved PARP expression increased, and claudin-5 and ZO-1 levels decreased compared with those in the OGD/R group. E-Cadherin expression decreased significantly after DEHP/OGD/R exposure compared with that after OGD/R; this decrease in expression was recovered by treatment with the COX-2 inhibitor indomethacin and antioxidant N-acetylcysteine. Exposure to DEHP exacerbated hypoxia-reoxygenation injury. The enhanced damage upon DEHP exposure was associated with increased oxidative stress and COX-2 expression, leading to E-cadherin downregulation and increased apoptosis.
A High-Quality Genome Resource for the Oak Wilt Pathogen Bretziella fagacearum
Authors: Chahal Karandeep , Mahey Mohit , Medina-Mora Carmen , Ahrendt Steven , Riley Robert , Lipzen Anna , Yan Juying , Savage Emily , Koriabine Maxim , Ng Vivian , Grigoriev Igor V. , Harrington Thomas C. , Patterson Eric L. , Miles Timothy D. , Sakalidis Monique L.
Published: October 2024

Bretziella fagacearum is a destructive vascular wilt fungal pathogen affecting oaks in the United States and Canada. The epidemiology of oak wilt varies across different geographical locations, indicating the need to investigate the population dynamics of B. fagacearum to discern potential differences in its genotypes using genomic tools. A good-quality genome of B. fagacearum is crucial as a reference for population genetics studies. Here, we report a high-quality genome of B. fagacearum isolate C519. The genome assembly consists of nine scaffolds, corresponding to the nine chromosomes, totaling 27,072,536 bp with a GC content of 47.29%. It is predicted to encode 7,554 proteins, which are annotated using RNA sequencing data from the same isolate. The circular mitochondrial genome consists of a chromosome of 174,403 bp with a GC content of 28.59% and contains 54 open reading frames, including 14 core genes, 28 tRNAs, 4 rRNAs, and 8 hypothetical proteins. The reference genome can enhance the understanding of molecular epidemiology and biology of B. fagacearum, aiding in identifying genetic variations and pathogen–host interactions and developing diagnostic tools and disease management strategies.

[Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2025.
Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis
Authors: McCann Tess , Sundaramurthi Husvinee , Walsh Ciara , Virdi Sanamjeet , Alvarez Yolanda , Sapetto‐Rebow Beata , Collery Ross F. , Carter Stephen P. , Moran Ailis , Mulholland Ruth , O'Connor John J. , Taylor Michael R. , Rauch Nora , Starostik Margaret R. , English Milton A. , Swaroop Anand , Geisler Robert , Reynolds Alison L. , Kennedy Breandán N.
Published: October 2024

Inherited retinal diseases (IRDs) are a rare group of eye disorders characterized by progressive dysfunction and degeneration of retinal cells. In this study, we characterized the raifteirí (raf) zebrafish, a novel model of inherited blindness, identified through an unbiased ENU mutagenesis screen. A mutation in the largest subunit of the endoplasmic reticulum membrane protein complex, emc1 was subsequently identified as the causative raf mutation. We sought to elucidate the cellular and molecular phenotypes in the emc1−/− knockout model and explore the association of emc1 with retinal degeneration. Visual behavior and retinal electrophysiology assays demonstrated that emc1−/− mutants had severe visual impairments. Retinal histology and morphometric analysis revealed extensive abnormalities, including thinning of the photoreceptor layer, in addition to large gaps surrounding the lens. Notably, photoreceptor outer segments were drastically smaller, outer segment protein expression was altered and hyaloid vasculature development was disrupted. Transcriptomic profiling identified cone and rod‐specific phototransduction genes significantly downregulated by loss of emc1. These data shed light on why emc1 is a causative gene in inherited retinal disease and how outer segment morphogenesis is regulated.
Immunotherapy and new treatments
Authors: Jakymec Yaroslav Andrew , Greiwe Justin , Bernstein Jonathan A.
Published: October 2024

Purpose of review

This review comes at a time where new techniques in immunotherapy administration are being developed, new innovations are being incorporated to standard techniques, and new regulations are being adopted regarding the creation and storage of allergen extracts. Prior to the release of updated practice parameters regarding allergic rhinitis and immunotherapies, this review article provides a synopsis of current recommendations, a comparison of the practices in the United States and those of Europe, and an examination of experimental methods that are being studied.

Recent findings

This article seeks to review and discuss the various methods of administration, build up schedules, efficacy, effect on other atopic symptoms, and safety associated with allergen immunotherapy.

Innovations in standard techniques, such as new allergoids for SCIT, appear to be effective in improving symptoms and increasing IgG levels for grass allergens. Data for newer techniques is less clear. There appears to be increased treatment-related adverse events for ILIT, worse symptom scores compared with placebo for IDIT, and insufficient studies regarding the effectiveness of EPIT for aeroallergens. New regulations seek to standardize the documentation, storage, and creation of allergen extracts.
Risk of Venous Thromboembolism in Adolescents Undergoing Pelvic Osteotomy: Insights From a Propensity-matched Retrospective Cohort Study
Authors: Mittal Mehul M. , Lee Tiffany M. , Acevedo Katalina V. , Hosseinzadeh Pooya
Published: October 2024

Background:

Pelvic osteotomies are surgical procedures that are commonly performed in adolescents and young adults to improve stability or correct various deformities. Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), are dreaded complications of any major procedure including pelvic osteotomies. Unlike adults, the incidence of DVT and need for prophylactic measures are not well understood in the adolescents. The purpose of this study is to understand the need for VTE prophylaxis in adolescents and determine if their risk profile aligns with adults, who have more established VTE prophylactic guidelines in place for these surgeries.

Methods:

This retrospective cohort study utilized data from the TriNetX Research Network, which includes records from over 80 healthcare organizations and more than 120 million patients. De-identified patient data from January 1, 2003, to March 1, 2024, were extracted using relevant ICD-9 and ICD-10 procedural codes. The study included 2 cohorts: patients aged 13 to 17 years (adolescents) and patients 18 years and older (adults) who underwent pelvic osteotomies. To control for confounding variables, propensity score matching was employed based on sex and relevant comorbidities, including diabetes mellitus, tobacco use, and overweight/obesity. Statistical significance was set at P<0.01.

Results:

A total of 2374 patients successfully matched in each cohort. Within 90 days following surgical intervention, adult patients had overall risks of 4.5%, 1.9%, and 5.9%, whereas adolescent patients had overall risks of 1.3%, 0.5%, and 1.4% for DVT (RR: 3.419), PE (RR: 4.182), and either DVT or PE (RR: 4.118), respectively.

Conclusions:

This study examines the rate of VTE in a large cohort of adolescents undergoing pelvic osteotomies. Although we found the rates to be lower in adolescents compared with adults, the high absolute risk in adolescents—above 1%, the threshold established in the literature for considering prophylaxis—underscores the need for tailored risk stratification strategies and targeted thromboprophylaxis protocols for this population.

Levels of Evidence:

Level III: case-control study or retrospective cohort study.
Therapeutic Potential of Mesenchymal Stem Cell–Derived Extracellular Vesicles Carrying MicroRNAs for Modulating Autophagy and Cellular Degeneration in Intervertebral Disc Degeneration
Authors: Wang LinFeng , Wang Yang , Jiao Jianhang , Jiang Weibo , Yu Tong , Wang Zhonghan , Li Mufeng , Wu Minfei , Pan Su
Published: October 2024

Study Design.

This research utilized bioinformatics and in vitro modeling to assess the effects of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) containing specific microRNAs (miRNAs) on the autophagy and degeneration of nucleus pulposus cells in intervertebral disc degeneration (IDD).

Objective.

To determine the therapeutic potential of MSC-EVs loaded with miRNAs in modulating pathologic changes in IDD.

Background.

IDD is characterized by changes in gene expression that contribute to cell degeneration and reduced disc integrity. MSC-EVs are known for their role in cellular communication and potentially reversing these degenerative processes.

Materials and Methods.

Key differentially expressed miRNAs and mRNAs in MSC-EVs were identified using bioinformatics analysis. Three miRNAs (miR-486-5p, miR-3648, and miR-1827) typically downregulated in IDD were selected for further study. The bone marrow-derived MSC-EVs used in this study were cultured in a two-dimensional environment. These MSC-EVs were isolated with the purpose of delivering the selected miRNAs to IDD nucleus pulposus cells in vitro, targeting specifically the upregulated genes (SMAD2, ESR1, MAVS, and MMP14) associated with autophagy and degeneration.

Results.

MSC-EV treatment led to significant downregulation of target genes, enhanced cellular proliferation, and decreased apoptosis and autophagy. Overexpression of these target genes produced the opposite effects, confirming the miRNAs’ regulatory roles.

Conclusions.

MSC-EVs carrying specific miRNAs can effectively modulate gene expression, reduce degenerative processes, and promote cellular proliferation in IDD, indicating a promising therapeutic strategy for treating IDD and potentially other degenerative diseases. Further investigations are warranted to explore MSC-EV applications in regenerative medicine.
KLF4 activates LATS2 to promote cisplatin sensitivity in ovarian cancer through DNA damage
Authors: Ma Ling , Zhao Xiaoting , Lu Xiang , Shen Jiahui , Huang Jiankang
Published: October 2024

We aimed to investigate the role of large tumor suppressor kinase 2 (LATS2) in cisplatin (DDP) sensitivity in ovarian cancer. Bioinformatic analysis explored LATS2 expression, pathways, and regulators. Quantitative reverse transcription-PCR measured LATS2 and KLF4 mRNA levels. Dual-luciferase and chromatin immunoprecipitation assays confirmed their binding relationship. Cell viability, half maximal inhibitory concentration (IC50) values, cell cycle, and DNA damage were assessed using CCK-8, flow cytometry, and comet assays. Western blot analyzed protein expression. The effect of LATS2 on the sensitivity of ovarian cancer to DDP was verified in vivo. LATS2 and KLF4 were downregulated in ovarian cancer, with LATS2 enriched in cell cycle, DNA replication, and mismatch repair pathways. KLF4, an upstream regulator of LATS2, bound to its promoter. Overexpressing LATS2 increased G1-phase cells, reduced cell viability and IC50 values, and induced DNA damage. Silencing KLF4 alone showed the opposite effect on LATS2 overexpression. Knocking out LATS2 reversed the effects of KLF4 overexpression on cell viability, cell cycle, IC50 values, and DNA damage in ovarian cancer cells. Inhibiting LATS2 inactivated the Hippo-YAP signaling pathway. In vivo experiments showed that overexpression of LATS2 enhanced the sensitivity of ovarian cancer to DDP. KLF4 activates LATS2 via DNA damage to enhance DDP sensitivity in ovarian cancer, providing a potential target for improving treatment outcomes.