bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of pulsars in the globular cluster omega centauri
Authors: Dai S , Johnston S , Kerr M , Berteaud J , Bhattacharyya B , Camilo F , Keane E 
Published: March 2023

ABSTRACT
We present the timing of the first five millisecond pulsars discovered in the globular cluster Omega Centauri and the discovery of a pulsar with a spin period of 3.68 ms. With a timing baseline of ∼3.5 yr we are able to measure the derivative of the spin frequency ($\dot{\nu }$) for the first five pulsars. Upper limits on the pulsar line-of-sight acceleration are estimated and compared with predictions based on analytical models of the cluster. We find that PSRs J1326−4728B and D show large negative accelerations, which are in tension with the minimum acceleration predicted by analytical models. We searched for pulsed γ-ray signals using 14.3 yr of data from the Fermi Large Area Telescope. Although we found no evidence for γ-ray pulsations, PSRs J1326−4728A, B, C, and E are associated with X-ray sources. This suggests that the observed γ-ray emission from Omega Centauri is likely caused by the emission of the ensemble of MSPs. Finally, the linearly polarized emission from PSR J1326−4728A yields a rotation measure of −18 ± 8 rad m−2.
Correlated motions in DNA: beyond base-pair step models of DNA flexibility
Authors: López-Güell Kim , Battistini Federica , Orozco Modesto 
Published: March 2023

AbstractTraditional mesoscopic models of DNA flexibility use a reductionist-local approach, which assumes that the flexibility of DNA can be expressed as local harmonic movements (at the base-pair step level) in the helical space, ignoring multimodality and correlations in DNA movements, which have in reality a large impact in modulating DNA movements. We present a new multimodal-harmonic correlated model, which takes both contributions into account, providing, with a small computational cost, results of an unprecedented local and global quality. The accuracy of this method and its computational efficiency make it an alternative to explore the dynamics of long segments of DNA, approaching the chromatin range.
MIRELLA: a mathematical model explains the effect of microRNA-mediated synthetic genes regulation on intracellular resource allocation
Authors: Cella Federica , Perrino Giansimone , Tedeschi Fabiana , Viero Gabriella , Bosia Carla , Stan Guy-Bart , Siciliano Velia 
Published: March 2023

Abstract
Competition for intracellular resources, also known as gene expression burden, induces coupling between independently co-expressed genes, a detrimental effect on predictability and reliability of gene circuits in mammalian cells. We recently showed that microRNA (miRNA)-mediated target downregulation correlates with the upregulation of a co-expressed gene, and by exploiting miRNAs-based incoherent-feed-forward loops (iFFLs) we stabilise a gene of interest against burden. Considering these findings, we speculate that miRNA-mediated gene downregulation causes cellular resource redistribution. Despite the extensive use of miRNA in synthetic circuits regulation, this indirect effect was never reported before. Here we developed a synthetic genetic system that embeds miRNA regulation, and a mathematical model, MIRELLA, to unravel the miRNA (MI) RolE on intracellular resource aLLocAtion. We report that the link between miRNA-gene downregulation and independent genes upregulation is a result of the concerted action of ribosome redistribution and ‘queueing-effect’ on the RNA degradation pathway. Taken together, our results provide for the first time insights into the hidden regulatory interaction of miRNA-based synthetic networks, potentially relevant also in endogenous gene regulation. Our observations allow to define rules for complexity- and context-aware design of genetic circuits, in which transgenes co-expression can be modulated by tuning resource availability via number and location of miRNA target sites.
The complex pathology of diabetic nephropathy in humans
Authors: Kriz Wilhelm , Löwen Jana , Gröne Hermann-Josef 
Published: March 2023

ABSTRACT
This review summarizes the pathomorphological sequences of nephron loss in human diabetic nephropathy (DN). The relevant changes may be derived from two major derangements. First, a failure in the turnover of the glomerular basement membrane (GBM) based on an increased production of GBM components by podocytes and endothelial cells leading to the thickening of the GBM and accumulation of worn-out GBM in the mesangium. This failure may account for the direct pathway to glomerular compaction and sclerosis based on the continuous deposition of undegraded GBM material in the mesangium. Second, an increased leakiness together with an increased propensity of glomerular capillaries to proliferate leads to widespread plasma exudations. Detrimental are those that produce giant insudative spaces within Bowman's capsule, spreading around the entire glomerular circumference and along the glomerulo-tubular junction onto the tubule resulting in tubular obstruction and retroactively to glomerulosclerosis. Tubular atrophy and interstitial fibrosis develop secondarily by transfer of the glomerular damage onto the tubule. Interstitial fibrosis is locally initiated and apparently stimulated by degenerating tubular epithelia. This leads to a focal distribution of interstitial fibrosis and tubular atrophy accompanied by a varying interstitial mononuclear cell infiltration. Spreading of fibrotic areas between intact nephrons, much less to the glomerulus, has not been encountered.
Effects of a pre- and probiotic mixture and an autogenous vaccine on growth performance in newly weaned piglets experimentally challenged with an enterotoxigenic Escherichia coli strain
Authors: Zeilinger Katharina , Wessels Anna G , Vahjen Wilfried , Zentek Jürgen 
Published: March 2023

Abstract
Beneficial effects of pro- and prebiotics in weanling piglets are of great interest in livestock production. Similarly, the use of specific vaccines is of interest as alternative to antibiotics to reduce postweaning performance losses. The aim of this study was the assessment of the effect of a dual-strain probiotic (Bacillus subtilis and Bacillus licheniformis) and a prebiotic (fructo-oligosaccharides) as well as the additional vaccination with an autogenous inactivated Escherichia coli vaccine on the performance of newly weaned piglets after experimental infection with an enterotoxigenic E. coli. Forty piglets at the age of 28 d were randomly allotted to one of five groups: nonchallenged control (NC); challenged positive control (PC); challenged and vaccinated (CV); challenged and diet supplemented with pre- and probiotic mix (CM) and challenged, diet supplemented with pro- and prebiotic mix and vaccinated (CMV). Piglets of CV and CMV were vaccinated parenterally prior to the trial at the age of 17 d. Compared to NC, the experimental infection with E. coli resulted in a significant reduction of body weight gain in both vaccinated groups (P = 0.045), which was associated with an impaired gain to feed ratio (P = 0.012), but not feed intake. In contrast, piglets in the group supplemented with pro- and prebiotics (group CM) were able to maintain their weight and had an average daily gain, which was not significantly different from groups NC and PC. No differences regarding body weight gain, feed intake, gain to feed ratio and fecal score were observed between groups during the 3rd and 4th week of the trial. A significant impairment of fecal consistency and frequency of diarrhea was observed related to the oral challenge when comparing PC and NC treatments (P = 0.024). Neither vaccine, nor supplementation with pro- and prebiotics were able to significantly improve fecal consistency, nor did they have a positive effect on the prevalence of diarrhea. The results show no positive synergistic effect of the specific combination of vaccine and pre- and probiotics used in this trial on performance and diarrhea. The results show that the concept of a combination of a specific vaccination and a probiotic with a prebiotic needs further investigation. In the sense of avoiding the use of antibiotics, this seems to be an attractive approach.
Behavior and brain size of larval zebrafish exposed to environmentally relevant concentrations of beta-methylamino-l-alanine
Authors: Reside Amanda M , Gavarikar Sana , Laberge Frédéric , Bernier Nicholas J 
Published: March 2023

Abstract
Harmful algal blooms (HABs) release toxic compounds in water and are increasing in frequency worldwide. The neurotoxin β-methylamino-l-alanine (BMAA) is released by HABs and has garnered much attention over the past 20 years due to its association with human neurodegenerative disorders, but its effects on wildlife are still largely unknown. This study characterized the effects of chronic exposure to environmentally relevant concentrations of BMAA on the behavior and brain size of developing zebrafish (Danio rerio). Zebrafish were continuously exposed to 0, 1, 10, or 100 µg/l waterborne BMAA between 0- and 5-days postfertilization (dpf) before the onset of exogenous feeding. At 5 dpf, locomotion and responses to vibrational and visual stimuli were assessed. Following behavioral testing, larvae body and brain size were measured. Survival between 0 and 5 dpf did not differ between treatments. Moreover, BMAA exposure did not affect thigmotaxis, startle response magnitude, habituation to repeated presentation of vibrational startling stimuli, or relative brain size. A moderate increase in overall activity was observed in larvae exposed to 10 μg/l BMAA under light, but this effect was not seen in dark conditions, indicating that visual processing may have been affected by chronic BMAA exposure. Thus, passive continuous exposure to environmentally relevant concentrations of BMAA prior to first feeding in zebrafish did not affect survival or selected measures used to represent brain development, anxiety, and motor reflexes, but a limited light-dependent effect on locomotion suggests targeted neurotoxicity within the visual system.
Adolescent exposure to low-dose Δ9-tetrahydrocannabinol depletes the ovarian reserve in female mice
Authors: Lim Jinhwan , Lee Hye-Lim , Nguyen Julie , Shin Joyce , Getze Samantha , Quach Caitlin , Squire Erica , Jung Kwang-Mook , Mahler Stephen V , Mackie Ken , Piomelli Daniele , Luderer Ulrike 
Published: March 2023

Abstract
Cannabis use by adolescents is widespread, but its effects on the ovaries remain largely unknown. Δ9-tetrahydrocannabinol (THC) exerts its pharmacological effects by activating, and in some conditions hijacking, cannabinoid receptors (CBRs). We hypothesized that adolescent exposure to THC affects ovarian function in adulthood. Peripubertal female C57BL/6N mice were given THC (5 mg/kg) or its vehicle, once daily by intraperitoneal injection. Some mice received THC from postnatal day (PND) 30–33 and their ovaries were harvested PND34; other mice received THC from PND30–43, and their ovaries were harvested PND70. Adolescent treatment with THC depleted ovarian primordial follicle numbers by 50% at PND70, 4 weeks after the last dose. The treatment produced primordial follicle activation, which persisted until PND70. THC administration also caused DNA damage in primary follicles and increased PUMA protein expression in oocytes of primordial and primary follicles. Both CB1R and CB2R were expressed in oocytes and theca cells of ovarian follicles. Enzymes involved in the formation (N-acylphosphatidylethanolamine phospholipase D) or deactivation (fatty acid amide hydrolase) of the endocannabinoid anandamide were expressed in granulosa cells of ovarian follicles and interstitial cells. Levels of mRNA for CBR1 were significantly increased in ovaries after adolescent THC exposure, and upregulation persisted for at least 4 weeks. Our results support that adolescent exposure to THC may cause aberrant activation of the ovarian endocannabinoid system in female mice, resulting in substantial loss of ovarian reserve in adulthood. Relevance of these findings to women who frequently used cannabis during adolescence warrants investigation.
The role of menopausal hormone therapy in the prevention and treatment of low bone density in perimenopausal and postmenopausal women
Authors: Shah Nandi , Ariel Danit 
Published: March 2023

Purpose of review
The purpose of this review is to summarize the evidence on the benefits of menopausal hormone therapy (MHT) for the maintenance of skeletal health, prevention of osteoporosis and related fractures in peri and postmenopausal women.

Recent findings
We will review the impact of estrogen on skeletal health as well as the physiology of bone loss during the perimenopause and postmenopause. We will then elucidate the data that include estrogen alone and combination of MHT to demonstrate that in the absence of contraindication, MHT should be considered as an option for the maintenance of skeletal health both when concomitant menopausal symptoms are present and when not.

Summary
It has been well established that estrogens maintain bone mineral density (BMD) and reduce fracture risk at all sites. However, the most extensively studied form of estrogen with established fracture prevention is oral doses of synthetic estrogens. Due to the reduced risk profile, lower doses of bioidentical oral or transdermal estrogens are often preferred in clinical practice. We will highlight the current data on improvement in BMD and fracture risk reduction, including differences in formulation, dose, and route of delivery, to support a provider in the clinical decision-making process.
SEVERE VISUAL LOSS DURING ANTI-VEGF INTRAVITREAL INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: TIMING, PROGNOSIS, AND OPTICAL COHERENCE TOMOGRAPHY FINDINGS
Authors: GRASSI MARIA OLIVA , MONTELEONE GIUSEPPINA , POZHARITSKIY NIKOLAI , MOLFETTA TERESA , BOSCIA GIACOMO , ALESSIO GIOVANNI , BOSCIA FRANCESCO 
Published: March 2023

Purpose:
Intravitreal injection (IVI) of anti–vascular endothelial growth factor (VEGF) is the standard of care for neovascular age-related macular degeneration (nAMD). However, a small subgroup of patients still experience severe visual impairment, which may be related to the number of IVI administered.

Methods:
This retrospective observational study analyzed data from patients with sudden severe visual decline (≥15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss between two consecutive IVIs) during anti-VEGF treatment for nAMD. Best-corrected visual acuity examination, optical coherence tomography (OCT), and OCT angiography (OCTA) were performed before every IVI and central macular thickness (CMT) and drug injected were collected.

Results:
1,019 eyes received anti-VEGF IVI for nAMD from December 2017 to March 2021. Severe VA loss occurred in 15.1% after a median of 6 (range 1–38) IVI. Ranibizumab was injected in 52.8% and aflibercept in 31.9% of cases. Functional recovery after 3 months was significant, without further improvement at 6 months. Visual prognosis relative to the percentage of CMT change showed better visual outcome in eyes with no substantial change in CMT compared with an increase of >20% or a decrease of >5%.

Conclusion:
In this first real-life study exploring severe VA loss during anti-VEGF treatment in patients with nAMD, it was found that it was not unusual for a ≥15 ETDRS letters loss to occur between two consecutive IVIs, often within 9 months of diagnosis and 2 months after the last IVI. Close follow-up and a proactive regimen should be preferred, at least in the first year.
FLUID–FLUID EXCHANGE AND EXTERNAL NEEDLE DRAINAGE WITH MINIMAL GAS VITRECTOMY ASSOCIATED WITH RETINAL DISPLACEMENT
Authors: Bansal Aditya , Escaf Luis C. , Lee Wei Wei , Muni Rajeev H. 
Published: March 2023

Purpose:
To determine whether fluid–fluid exchange (endodrainage) or external needle drainage can result in retinal displacement following minimal gas vitrectomy (MGV) with no fluid–air exchange for rhegmatogenous retinal detachment repair.

Methods:
Two patients with macula-off rhegmatogenous retinal detachment underwent MGV with and without segmental buckle. First case had MGV with segmental buckle (MGV-SB), along with endodrainage, whereas the second case had MGV only with external fluid drainage. At the completion of surgery, the patient was immediately log rolled to face down for 6 hours followed by positioning to the break.

Results:
Both patients achieved retinal reattachment, and postoperative widefield fundus autofluorescence imaging demonstrated a low-integrity retinal attachment with retinal displacement.

Conclusion:
Iatrogenic fluid drainage techniques, such as fluid–fluid exchange or external needle drainage during MGV (without fluid–air exchange), may result in retinal displacement. Allowing the retinal pigment epithelial pump to reabsorb the fluid naturally may reduce the risk of retinal displacement.
SEVERE MULTIFOCAL PLACOID CHORIORETINITIS ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITOR THERAPY
Authors: Yu Jeffrey J. , Everett Lesley , Sassalos Therese M. , Johnson Mark W. 
Published: March 2023

Purpose:
To report a case of severe bilateral multifocal placoid chorioretinitis in a patient receiving ipilimumab and nivolumab therapy for metastatic melanoma.

Methods:
Retrospective, observational case report.

Results:
A 31-year-old woman on ipilimumab and nivolumab for metastatic melanoma developed severe multifocal placoid chorioretinitis in both eyes. The patient was started on topical and systemic corticosteroid therapy, and immune checkpoint inhibitor therapy was paused. After resolution of ocular inflammation, the patient was restarted on immune checkpoint inhibitor therapy without return of ocular symptoms.

Conclusion:
Extensive multifocal placoid chorioretinitis may occur in patients undergoing immune checkpoint inhibitor therapy. Some patients with immune checkpoint inhibitor–related uveitis may successfully resume immune checkpoint inhibitor therapy under close collaboration with the treating oncologist.
Regional analgesia techniques for lumbar spine surgery: a frequentist network meta-analysis
Authors: Hong Boohwi , Baek Sujin , Kang Hyemin , Oh Chahyun , Jo Yumin , Lee Soomin , Park Seyeon 
Published: March 2023

Background:
Various regional analgesia techniques are used to reduce postoperative pain in patients undergoing lumbar spine surgery. Traditionally, wound infiltration (WI) with local anesthetics has been widely used by surgeons. Recently, other regional analgesia techniques, such as the erector spinae plane block (ESPB) and thoracolumbar interfascial plane (TLIP) block, are being used for multimodal analgesia. The authors aimed to determine the relative efficacy of these using a network meta-analysis.

Materials and methods:
The authors searched PubMed, EMBASE, the Cochrane Controlled Library, and Google Scholar databases to identify all randomized controlled trials that compared the analgesic efficacy of the following interventions: ESPB, TLIP block, WI technique, and controls. The primary endpoint was postoperative opioid consumption during the first 24 hours after surgery, while the pain score, estimated postoperatively at three different time periods, was the secondary objective.

Results:
The authors included 34 randomized controlled trials with data from 2365 patients. TLIP showed the greatest reduction in opioid consumption compared to controls [mean difference (MD) =−15.0 mg; 95% CI: −18.8 to −11.2]. In pain scores, TLIP had the greatest effect during all time periods compared to controls (MD=−1.9 in early, −1.4 in middle, −0.9 in late). The injection level of ESPB was different in each study. When only surgical site injection of ESPB was included in the network meta-analysis, there was no difference compared with TLIP (MD=1.0 mg; 95% CI: −3.6 to 5.6).

Conclusions:
TLIP showed the greatest analgesic efficacy after lumbar spine surgery, in terms of postoperative opioid consumption and pain scores, while ESPB and WI are also alternative analgesic options for these surgeries. However, further studies are needed to determine the optimal method of providing regional analgesia after lumbar spine surgery.
Literature review: are NSAIDs harmful and is acetaminophen well tolerated?
Authors: Abbasi Momen , Teakell Jade 
Published: March 2023

Purpose of review
On the basis of previous literature, NSAID use is typically avoided in patients at risk for kidney disease, while acetaminophen has generally been considered well tolerated. However, the extent of NSAID effect on the kidneys is not clear, especially in chronic kidney disease (CKD), and the concerns about the safety of acetaminophen have been rising. In this review, we will discuss the latest evidence of the effects of NSAIDs and acetaminophen in the context of nephrology and hypertension.

Recent findings
The risk of acute kidney injury (AKI) by NSAIDs is higher with longer courses and in the presence of several factors such as older age, diabetes mellitus, lower eGFR, diuretic use and cardiovascular disease. The timing of NSAID use in relation to the onset of AKI may affect its progression. Regular NSAID use could be associated with an increased incidence of CKD, but the relation between NSAID use and CKD progression is less clear. Regular acetaminophen use was associated with increased SBP, while its use could have a renoprotective effect in certain situations.

Summary
In patients at risk of kidney disease, NSAIDs may be used cautiously after discussing possible adverse effects. Regular acetaminophen use should be reassessed in patients with uncontrolled hypertension.
Management of the brachial plexus in head and neck cancer
Authors: Fockens M. Matthijs , Kraak Jeroen T. , Leemans C. René , Eerenstein Simone E.J. 
Published: March 2023

Purpose of review
The brachial plexus is an important anatomical structure that is regularly encountered by head and neck surgeons and radiation oncologists. Surgical or radiation-induced brachial plexus injury have great impact on arm function and quality of life. Anatomical variations and management of the brachial plexus in head and neck cancer treatment are discussed.

Recent findings
The brachial plexus consists of spinal roots from C5–C8 and T1. The most prevalent anatomical variations in brachial plexus anatomy include the prefixed brachial plexus (additional contribution from C4) in 11%, the roots of C5 and C6 piercing the belly of the anterior scalene muscle in 6.8%, and presence of the scalenus minimus muscle in 4.1–46%. Due to its location, the brachial plexus is at risk of inadvertent division or neuropraxia during surgical procedures such as neck dissection or robot-assisted transaxillary thyroid surgery (RATS). In case of inadvertent division, nerve reconstruction surgery is warranted and may lead to improved function. The risk of radiation-induced brachial plexus injury is dose-dependent and occurs in approximately 12–22%. Currently, no successful treatment options exist for radiation-induced injury.

Summary
Knowledge of anatomical variations is important for head and neck surgeons to minimize the risk of brachial plexus injury. Limiting radiation therapy dose to the brachial plexus is desirable to decrease the risk of brachial plexus injury.