bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear dynamics, coexistence of attractors and microcontroller implementation of a modified Helmholtz Jerk oscillator
Authors: Fangnon R , Kamdoum Tamba Victor , Miwadinou C H , Monwanou A V , Chabi Orou J B
Published: July 2023

In this work, we converted a two-dimensional modified Helmholtz oscillator into a three-dimensional modified Helmholtz jerk oscillator. The study of the stability of the fixed points is made and by using the theorem of Hopf, the condition of existence of the bifurcation of Hopf is sought. By numerical simulations relating to the diagrams of the basin of parameters, attraction, bifurcation, the Lyapunov exponents and the phase portrait, the global dynamics as well as the coexistence of the attractors of the system are analyzed. This study revealed that the considered modified Jerk Helmholtz oscillator can generate Hopf bifurcation, bistable limit cycles, coexistence of chaotic and periodic attractors for appropriate choices of system parameter values. The microcontroller based implementation of the modified Jerk Helmholtz oscillator is proposed to experimentally verify the obtained analytical and numerical results. Finally, to control the amplitude of the Lyapunov attractor and exponent, we added two new parameters in the modified Helmholtz jerk oscillator.
Reduction of pyocyanin synthesis and antibiotic resistance in Pseudomonas aeruginosa by low concentration ethanol
Authors: Jiang Shijie , Deng Yunfeng , Long Zhijian , Liu Peng , Hong Jing , Wei Tingzhou , Zhang Yu , Sun Shanshan , Zhuo Shaoyuan , Shang Liguo
Published: July 2023

Pseudomonas aeruginosa is a common bacteria that may cause a wide range of severe illnesses in humans. One of the nonantibiotic therapies, antivirulence factor therapy, has attracted ongoing interest. Screening for and investigating bacterial virulence factor inhibitors is critical for the development of antivirulence factor treatments. Pyocyanin is P. aeruginosa’s distinctive pigment, and it plays a key role in infection. The impact of low concentration ethanol on pyocyanin production was investigated in this research. Pyocyanin production was found both subjectively and quantitatively. The effects of ethanol on the expression of pyocyanin production genes were studied using qRT-PCR and western blotting. The findings demonstrated that low concentrations of ethanol (as little as 0.1%) greatly suppressed pyocyanin production without affecting P. aeruginosa growth. The degree of inhibition increased as the ethanol contentration rose. Ethanol inhibits the expression of genes involved in pyocyanin production. This inhibitory impact was mostly seen at the protein level. Further research revealed that ethanol increased the expression of the post-transcriptional regulator RsmA, which inhibits pyocyanin production. Given the favorable relationship between pyocyanin production and antibiotic resistance, the impact of low concentration ethanol on various antibiotics was investigated. Ethanol lowered antibiotic resistance in P. aeruginosa, presumably by inhibiting pyocyanin.
Engaging Nigerian Older Persons in Neighborhood Environment Assessment for Physical Activity Participation: A Citizen Science Project
Authors: Odeyemi Emmanuel , Chesser Stephanie , King Abby C , Porter Michelle M
Published: July 2023

Background and Objectives

Global organizations are advocating that older persons’ voices should guide communities in age-friendly design. An important aspect of age friendliness to enable daily function and health is ensuring that physical activity can occur, regardless of age, within local neighborhoods.

Research Design and Methods

This study used a specific citizen science approach, Our Voice, to engage a sample (N = 13) of older adults (60 or older) in Festac Town, Nigeria. The citizen scientists’ roles were to assess and identify how different aspects of the neighborhood environment act as supports or barriers to their physical activity participation. They were individually enabled using a tablet-based mobile application called the Stanford Healthy Neighborhood Discovery Tool to record a total of 156 geocoded photos and 151 commentaries of neighborhood environmental features that facilitate or hinder physical activity in and around their neighborhoods. In a guided process, the following occurred: collaborative discussions of findings with other citizen scientists to determine common targets, setting of priority targets for change, and brainstorming strategies and solutions.

Results

Facilitators of physical activity included: pedestrian and traffic facilities (e.g., traffic lights, walkways); green areas and parks; multigenerational community features (e.g., programs/facilities); opportunities for social connection (e.g., neighborhood associations, churches); safety of destinations and services; and public toilets. Barriers to physical activity included: hazardous walkways/traffic; noise pollution; refuse, selling of public parks; crime (e.g., kidnapping, criminal hideouts); no safe drinking water; and ageism. The priorities for changes were social connectivity; improved pedestrian and traffic facilities; and green and beautiful environments.

Discussion and Implications

In this study, both physical and social aspects of the environment were deemed important for older Nigerians to enable physical activity in their local community. This approach has a promise for age-friendly initiatives seeking local changes by meaningfully engaging older adults.
Association of red blood cell distribution width with hospital admission and in-hospital mortality across all-cause adult emergency department visits
Authors: Hong Woo Suk , Rudas Akos , Bell Elijah J , Chiang Jeffrey N
Published: July 2023

Objectives

To test the association between the initial red blood cell distribution width (RDW) value in the emergency department (ED) and hospital admission and, among those admitted, in-hospital mortality.

Materials and Methods

We perform a retrospective analysis of 210 930 adult ED visits with complete blood count results from March 2013 to February 2022. Primary outcomes were hospital admission and in-hospital mortality. Variables for each visit included demographics, comorbidities, vital signs, basic metabolic panel, complete blood count, and final diagnosis. The association of each outcome with the initial RDW value was calculated across 3 age groups (<45, 45–65, and >65) as well as across 374 diagnosis categories. Logistic regression (LR) and XGBoost models using all variables excluding final diagnoses were built to test whether RDW was a highly weighted and informative predictor for each outcome. Finally, simplified models using only age, sex, and vital signs were built to test whether RDW had additive predictive value.

Results

Compared to that of discharged visits (mean [SD]: 13.8 [2.03]), RDW was significantly elevated in visits that resulted in admission (15.1 [2.72]) and, among admissions, those resulting in intensive care unit stay (15.3 [2.88]) and/or death (16.8 [3.25]). This relationship held across age groups as well as across various diagnosis categories. An RDW >16 achieved 90% specificity for hospital admission, while an RDW >18.5 achieved 90% specificity for in-hospital mortality. LR achieved a test area under the curve (AUC) of 0.77 (95% confidence interval [CI] 0.77–0.78) for hospital admission and 0.85 (95% CI 0.81–0.88) for in-hospital mortality, while XGBoost achieved a test AUC of 0.90 (95% CI 0.89–0.90) for hospital admission and 0.96 (95% CI 0.94–0.97) for in-hospital mortality. RDW had high scaled weights and information gain for both outcomes and had additive value in simplified models predicting hospital admission.

Discussion

Elevated RDW, previously associated with mortality in myocardial infarction, pulmonary embolism, heart failure, sepsis, and COVID-19, is associated with hospital admission and in-hospital mortality across all-cause adult ED visits. Used alone, elevated RDW may be a specific, but not sensitive, test for both outcomes, with multivariate LR and XGBoost models showing significantly improved test characteristics.

Conclusions

RDW, a component of the complete blood count panel routinely ordered as the initial workup for the undifferentiated patient, may be a generalizable biomarker for acuity in the ED.
An evaluation of the quality of Annona muricata leaf products
Authors: Jocelin Chan Wai-Jo , Harnett Joanna E , Meroni Alexandra , McLachlan Andrew J , Hanrahan Jane R
Published: July 2023

Objectives

Annona muricata, also known as graviola, is traditionally used for the treatment of a range of disorders including cancer. Interest in A. muricata use has increased in recent years. This study investigated the quality and safety of a selection of commercially available A. muricata leaf products.

Methods

Seven commercially available products were purchased via online shopping sites. Each product was assessed for quality indicators including weight variation, quantification of the bioactive constituent annonacin, presence of annonaceous acetogenins and contaminants. The samples were evaluated by thin-layer chromatography, high-performance liquid chromatography, liquid chromatography–mass spectroscopy, low-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Microbial analysis was carried out in accordance with the British Pharmacopoeia. Heavy metals were analysed by inductive coupled plasma mass spectrometry.

Key findings

Of the seven products analysed, one product contained less than half of the content stated on the label. The labelled dosage recommendation varied between products. There was a high variation in annonacin concentration (1.05–3.09 mg/g) and the presence of annonaceous acetogenins. One of the products was found to have a total aerobic microbial count above the United States Pharmacopoeia limit.

Conclusions

The variation in the indicators of quality and safety of commercially available A. muricata leaf products tested have implications for clinicians and people living with cancer who use these herbal products.
Multitarget therapy with a corticosteroid, cyclosporine and mycophenolate mofetil for idiopathic membranous nephropathy: a prospective randomized controlled trial
Authors: Duan Yajuan , Bai Yu , Guo Weikang , Wang Liyan , Dai Wendi , Guo Wang , Huang Hongdong , Liu Wenhu , Diao Zongli
Published: July 2023

Background

The effectiveness of multitarget combination therapy with a corticosteroid, cyclosporine and mycophenolate mofetil for idiopathic membranous nephropathy (IMN) is unclear. In the present study, we aimed to compare the efficacy and safety of multitarget therapy with a cyclical corticosteroid–cyclophosphamide regimen in patients with IMN.

Methods

This was a single-centre, prospective, randomized, controlled trial. We randomly assigned patients with IMN to receive multitarget therapy (a combination of prednisone, cyclosporine and mycophenolate mofetil) or 6-month cyclical treatment with a corticosteroid and cyclophosphamide. The study patients were followed up for 12 months. The primary outcome was a composite of complete or partial remissions at 12 months. Adverse events were also assessed.

Results

The study cohort comprised 78 patients, 39 of whom received multitarget therapy and the other 39 cyclical alternating treatment with a corticosteroid and cyclophosphamide. At 12 months, 31 of 39 patients (79%) in the multitarget therapy group and 34 of 39 (87%) in the corticosteroid–cyclophosphamide group had achieved complete or partial remissions (relative risk 0.93; 95% confidence interval 0.72–1.21; P = .85; log-rank test). The prevalence of adverse events was significantly lower in the multitarget therapy group than in the corticosteroid–cyclophosphamide group [46% (18 of 39) vs 74% (29 of 39); P < .05].

Conclusions

Multitarget therapy for IMN patients is noninferior to cyclical alternating treatment with corticosteroid and cyclophosphamide in inducing proteinuria remission and has a better safety profile than the corticosteroid–cyclophosphamide combination.
Charitable giving and intermediation: a principal agent problem with hidden prices
Authors: Chlaß Nadine , Gangadharan Lata , Jones Kristy
Published: July 2023

Donations are often made through charitable intermediaries that can fund themselves from these same donations. After intermediation, only a fraction of the amount donated may reach the intended beneficiary. The price of charitable output is therefore higher after intermediation than if donors donated directly toward the end cause. At the same time, this price is hidden from donors since they cannot verify how much intermediaries pass on. We show that while donors reduce their donation in intermediation itself, and also reduce their donation because they expect the price of charitable output to increase, both reactions are either fully or partly compensated by their ethical preferences for the recipient’s rights. Charitable output, therefore, can be a Giffen-good.
Acquiring Land from Traditional Communities: Bottlenecks, Misallocation and Second-Best Considerations
Authors: Ghatak Maitreesh , Mookherjee Dilip
Published: July 2023

We discuss reasons why traditional rural communities may be reluctant to voluntarily relinquish their access to land despite being compensated at market prices, thereby limiting the scope for reallocating land to more productive uses in agriculture or urban development. Owing to financial market imperfections, insurance and collateral benefits of land ownership imply that welfare-optimal land allocations may not maximize productive efficiency, even if distributive or environmental considerations are ignored. We provide some suggestive evidence and discuss implications for land acquisition policy.
Utilising trusts in Swiss divorces?
Authors: Suter Claudia , Korradi Anja
Published: July 2023

What do trusts and divorces have in common? They are expensive. One might thus wonder why the two should be combined. Admittedly, establishing a trust is not a realistic option for most divorcing couples. For some (wealthy) spouses, however, a trust could provide a number of economic and other benefits worth considering. This article points out the benefits of using a trust in the context of a Swiss divorce and sets out the framework for its permissibility. For this, we assess the potential and constraints of Swiss marital and divorce agreements as well as the scope of review exercised by Swiss divorce courts.
Bladder Temperature During Neonatal Targeted Temperature Management
Authors: Buccione Emanuele , Chiavaroli Valentina , Scarponcini Fornaro Davide , Toracchio Erica , Cicioni Paola , Rasero Laura , Bambi Stefano , Di Valerio Susanna
Published: July 2023

Background:

Neonatal encephalopathy is a clinical condition of altered neurological function in the first days of life. Targeted temperature management (TTM) is a validated approach to mitigate neurologic sequelae. Current literature suggests using rectal or esophageal site to assess temperature during TTM, but few studies focused on the best and the less invasive site to evaluate the temperature. This case report describes the performance of the bladder temperature monitoring during TTM.

Clinical Findings:

A female newborn was born at 39 weeks' gestational age plus 4 days. At delivery, the newborn was in cardiorespiratory arrest.

Primary Diagnosis:

After performing cardiopulmonary resuscitation and neurological examination, a hypoxic–ischemic encephalopathy was diagnosed.

Interventions:

After about 2 hours from birth, the newborn underwent TTM.

Outcomes:

A total of 4642 measurements of rectal temperature and 4520 measurements of bladder temperature were collected. Agreement between the 2 sites was statistically significant with a mean difference of 0.064°C ± 0.219 (95% confidence interval, −0.364 to 0.494); F = 47.044; and P value of less than .001. Furthermore, difference between rectal and bladder sites was not influenced by patient's urine output (F = 0.092, P = .762).

Practice Recommendations:

Bladder temperature seems to have a good reliability and not to be inferior to the other assessment site currently used. Using bladder catheter with temperature sensor could reduce the number of devices, ensure safer stabilization, and decrease treatment downtime.
Prenatal Screening for Microdeletions and Rare Autosomal Aneuploidies
Authors: FIORENTINO DESIREE , DAR PE’ER
Published: July 2023

Noninvasive prenatal screening with cell-free DNA is now considered a first-line screening for common aneuploidies. Advancements in existing laboratory techniques now allow to interrogate the entirety of the fetal genome, and many commercial laboratories have expanded their screening panels to include screening for rare autosomal aneuploidies and copy number variants. Here, we review the currently available data on the performance of fetal cell-free DNA to detect rare autosomal aneuploidies and copy number variants that are associated with clinically significant microdeletion and microduplication syndromes and the current position of medical societies on routine screening for these syndromes.
Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort*
Authors: Kucher Nicholas M. , Marquez Alexandra M. , Guerguerian Anne-Marie , Moga Michael-Alice , Vargas-Gutierrez Mariella , Todd Mark , Honjo Osami , Haller Christoph , Goco Geraldine , Floh Alejandro A.
Published: July 2023

OBJECTIVES:

During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined.

DESIGN:

Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion.

SETTING:

PICU and cardiac ICU in a quaternary-care center.

PATIENTS:

Patients 0–18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014–2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37–101 mcg/kg), with the last dose given 6 minutes (2–16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO (p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, –0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance.

CONCLUSIONS:

There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.
Beta-HCG levels and ovarian ultrasonography results among non-pregnant women of reproductive age in Port Harcourt, Nigeria
Authors: Agonsi Celine Chibuzo , Anacletus Francis , Aluko Joel , Eleke Chinemerem , Samuel Joy
Published: July 2023

Background

Certain ovarian cancers previously more common in postmenopausal women are now increasingly observed in women of reproductive age. The research on using β-HCG as a diagnostic biomarker for ovarian cancer in women of reproductive age is ongoing. This particular study assessed the level of serum β-HCG in non-pregnant women of reproductive age and determined its potential association with suspicious ovarian ultrasonography results in Port Harcourt, Nigeria.

Material and methods

This study utilized a descriptive-analytic design on a quota sample of 224 diagnostic case notes of women aged 18-40 years obtained from eight diagnostic centres. Data collection involved a data extraction form. Data analysis employed descriptive statistics, Chi-square, Fisher’s exact test, and Odds Ratio at 95% confidence and 5% significance levels.

Results

About 5.8% of the participants exhibited detectable levels of serum β-HCG above 5 IU/L (World Health Organization reference) at a mean concentration of 5.87 (±1.75) IU/L. About 4.0% of the participants had suspicious ovarian lesions identified through ultrasonography. Participants with elevated serum β-HCG levels above the WHO reference were 59 times more likely to have suspicious ovarian lesions, with an odds ratio of 59.4 (95%CI: 12.3–287.8, p = 0.001). There was a significant association between serum β-HCG level and age (p = 0.041) as well as parity (p < 0.001).

Conclusions

This study demonstrated that Serum β-HCG levels above the WHO reference were associated with suspicious ovarian lesions. Non-pregnant women should undergo serum β-HCG testing at least yearly to facilitate the early detection of ovarian anomalies.
Validation of Utstein-Based score to predict Return Of Spontaneous Circulation (UB-ROSC) in patients with out-of-hospital cardiac arrest
Authors: Caputo Maria Luce , Baldi Enrico , Burkart Roman , Wilmes André , Cresta Ruggero , Benvenuti Claudio , Cianella Roberto , Primi Roberto , Currao Alessia , Bendotti Sara , Compagnoni Sara , Gentile Francesca Romana , Anselmi Luciano , Savastano Simone , Klersy Catherine , Auricchio Angelo
Published: July 2023

Background

Prediction of probability of return of spontaneous circulation (ROSC) during out-of-hospital cardiac arrest (OHCA) is one of the biggest challenge in resuscitation science. The Utstein Based-ROSC (UB-ROSC) score has been developed to predict ROSC in OHCA’s victims. Aim of the study was to validate UB-ROSC score using two large Utstein-based OHCA registries: the SWiss REgistry of Cardiac Arrest (SWISSRECA) and the Lombardia Cardiac Arrest Registry (Lombardia CARe), northern Italy.

Methods

Consecutive OHCA of any etiology occurring between January 1st, 2019 and December 31stand registered in 2 large national registries were included in a prospectively designed validation study. For model validation, a model area under the ROC curve (AUC ROC) for discrimination, using 10-fold cross-validation was computed. The score was plotted against the survival to hospital admission.

Results

14,715 patients were included in the study. A sustained ROSC was obtained in 3,151 patients (21%). Overall, UB-ROSC model showed a good discrimination (AUC 0.72, 95% CI 0.71-0.73). Shape of risk predicted by the model was almost linear and the model resulted well calibrated. In the low likelihood subgroup of UB-ROSC, only 9% of patients achieved a ROSC. This proportion raised to 35% for UB-ROSC score between −18 and 12 (OR 5.3, 95% CI 2.9-9.4, P<0.001). Finally, in 85% of patients with UB-ROSC values of more than or equal to 13 a ROSC was obtained (OR 52.1, 95%CI 15.6-173.0, P <0.001).

Conclusions

UB-ROSC score may represent a reliable tool to predict ROSC probability. Its application may help the decision-making process providing a realistic stratification of probability of ROSC achievement.

Clinical perspectives

What is new?

-

UB-ROSC is the unique Utstein-based score designed to help EMS staff to stratify patient’s probability of ROSC before treating the patient.

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In this validation study, UB-ROSC score was verified in a cohort of more than 14,000 OHCA and confirmed a very high power in discrimination of ROSC probability

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The score is very user-friendly and may be considered a helpful tool for EMS in the decision-making process when approaching OHCA victims.

What are the clinical implications?

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Sudden cardiac death is the leading causes of death worldwide and substantially contribute to loss of health and excess health system costs.

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Development and validation of models to stratify probability of survival are increasingly necessary in the decision-making process, particularly in a pre-hospital setting, to offer a realistic expectation of survival and eventually to terminate resuscitation attempts.
Direct measurements of luminal Ca2+with endo-lysosomal GFP-aequorin reveal functional IP3receptors
Authors: Calvo B , Torres-Vidal P , Delrio-Lorenzo A , Rodriguez C , Aulestia FJ , Rojo-Ruiz J , McVeigh BM , Moiseenkova-Bell V , Yule DI , Garcia-Sancho J , Patel S , Alonso MT
Published: July 2023

Endo-lysosomes are considered acidic Ca2+stores but direct measurements of luminal Ca2+within them are limited. Here we report that the Ca2+-sensitive luminescent protein aequorin does not reconstitute with its cofactor at highly acidic pH but that a significant fraction of the probe is functional within a mildly acidic compartment when targeted to the endo-lysosomal system. We leveraged this probe (ELGA) to report Ca2+dynamics in this compartment. We show that Ca2+uptake is ATP-dependent and sensitive to blockers of endoplasmic reticulum Ca2+pumps. We find that the Ca2+mobilizing messenger IP3which typically targets the endoplasmic reticulum evokes robust luminal responses in wild type cells, but not in IP3receptor knock-out cells. Responses were comparable to those evoked by activation of the endo-lysosomal ion channel TRPML1. Stimulation with IP3-forming agonists also mobilized the store in intact cells. Super-resolution microscopy analysis confirmed the presence of IP3receptors within the endo-lysosomal system, both in live and fixed cells. Our data reveal a physiologically-relevant, IP3-sensitive store of Ca2+within the endo-lysosomal system.
Chromosomal-level genome assembly ofPopulus davidiana
Authors: Chen Liyang , Jiang Yuanzhong , Shi Tingting , Jia Changfu , Long Zhiqin , Zhang Xinxin , Sang Yupeng , Liu Jianquan , Wang Jing
Published: July 2023

Despite the population structure and genetic differentiation ofP. davidianahas been reported, little is known about theP. davidianagenome characterization with the genomes assembled at the chromosome level. As one of the most widely distributed and ecologically important tree species in China,P. davidianais an excellent resource to understand population adaption to climate and environment change. Here we present a high-quality assembly based on long-read sequences and Hi-C data. This assembly is assembled into 19 contiguous chromosomes which provides a powerful tool for future association studies.
Evolutionary genomics predicts adaptive genetic and plastic gene expression responses to climate change in a key alpine forest tree species
Authors: Long Zhiqin , Sang Yupeng , Feng Jiajun , Zhang Xinxin , Shi Tingting , Zhang Lushui , Mao Kangshan , Rieseberg Loren H. , Liu Jianquan , Wang Jing
Published: July 2023

Despite widespread biodiversity loss, our understanding of how species and populations will respond to accelerated climate change remains limited. In this study, we predict the evolutionary responses ofPopulus lasiocarpa, a key alpine forest tree species primarily found in the mountainous regions of a global biodiversity hotspot, to climate change. We accomplish this by generating and integrating a new reference genome forP. lasiocarpa, re-sequencing data for 200 samples, and gene expression profiles for leaf and root tissue following exposure to heat and waterlogging. Analyses of the re-sequencing data indicate that demographic dynamics, divergent selection, and long-term balancing selection have shaped and maintained genetic variation within and between populations over historical timescales. In examining genomic signatures of contemporary climate adaptation, we found that haplotype blocks, characterized by inversion polymorphisms that suppress recombination, play a crucial role in clustering environmentally adaptive variations. Comparison of evolved and plastic gene expression show that genes with expression plasticity generally align with evolved responses, highlighting the adaptive role of plasticity. Lastly, we incorporated local adaptation, migration, genetic load, and plasticity responses into our predictions of population-level climate change risks. Our findings reveal that western populations, primarily distributed in the Hengduan Mountains—a region known for its environmental heterogeneity and significant biodiversity—are the most vulnerable to climate change and should be prioritized for conservation and management. Overall, our study advances understanding of the relative roles of long-term natural selection, local environmental adaptation, and immediate plasticity responses in driving evolutionary adaptation to climate change in keystone species.
Does enforcing glenohumeral joint stability matter? A new rapid muscle redundancy solver highlights the importance of non-superficial shoulder muscles
Authors: Belli Italo , Joshi Sagar , Prendergast J. Micah , Beck Irene , Santina Cosimo Della , Peternel Luka , Seth Ajay
Published: July 2023

The complexity of the human shoulder girdle enables the large mobility of the upper extremity, but also introduces instability of the glenohumeral (GH) joint. Shoulder movements are generated by coordinating large superficial and deeper stabilizing muscles spanning numerous degrees-of-freedom. How shoulder muscles are coordinated to stabilize the movement of the GH joint remains widely unknown. Musculoskeletal simulations are powerful tools to gain insights into the actions of individual muscles and particularly of those that are difficult to measure. In this study, we analyze how enforcement of GH joint stability in a musculoskeletal model affects the estimates of individual muscle activity during shoulder movements. To estimate both muscle activity and GH stability from recorded shoulder movements, we developed a Rapid Muscle Redundancy (RMR) solver to include constraints on joint reaction forces (JRFs) from a musculoskeletal model. The RMR solver yields muscle activations and joint forces by minimizing the weighted sum of squared-activations, while matching experimental motion. We implemented three new features: first, computed muscle forces include active and passive fiber contributions; second, muscle activation rates are enforced to be physiological, and third, JRFs are efficiently formulated as linear functions of activations. Muscle activity from the RMR solver without GH stability was not different from the computed muscle control (CMC) algorithm and electromyography of superficial muscles. The efficiency of the solver enabled us to test 3600 trials sampled within the uncertainty of the experimental movements to test the differences in muscle activity with and without GH joint stability enforced. We found that enforcing GH stability significantly increases the estimated activity of the rotator cuff muscles but not of most superficial muscles. Therefore, a comparison of shoulder model muscle activity to EMG measurements of superficial muscles alone is insufficient to validate the activity of rotator cuff muscles estimated from musculoskeletal models.
Competition between stochastic neuropeptide signals calibrates the rate of satiation
Authors: Zhang Stephen X. , Kim Angela , Madara Joseph C. , Zhu Paula K. , Christenson Lauren F. , Lutas Andrew , Kalugin Peter N. , Jin Yihan , Pal Akash , Tian Lin , Lowell Bradford B. , Andermann Mark L.
Published: July 2023

We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and αMSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP, but the messenger’s spatiotemporal dynamics and role in energy balance are controversial. We show that AgRP axon stimulation in the paraventricular hypothalamus evokes probabilistic and spatially restricted NPY release that triggers stochastic cAMP decrements in downstream MC4R-expressing neurons (PVHMC4R). Meanwhile, POMC axon stimulation triggers stochastic, αMSH-dependent cAMP increments. NPY and αMSH competitively control cAMP, as reflected by hunger-state-dependent differences in the amplitude and persistence of cAMP transients evoked by each peptide. During feeding bouts, elevated αMSH release and suppressed NPY release cooperatively sustain elevated cAMP in PVHMC4Rneurons, thereby potentiating feeding-related excitatory inputs and promoting satiation across minutes. Our findings highlight how state-dependent integration of opposing, quantal peptidergic events by a common biochemical target calibrates energy intake.
Skeletal progenitor LRP1-mediated endocytosis is critical for synovial joint formation and bone growth
Authors: Alhashmi Mohammad , Gremida Abdulrahman ME , Al-Maslamani Noor A , Liu Ke , Sutherland Hazel , Wilson Peter , Clegg Peter , van ’t Hof Robert J , Bou-Gharios George , Yamamoto Kazuhiro
Published: July 2023

The layer of stem cells surrounding developing limbs is essential for bone formation and regeneration. Our work addresses the critical question of how these stem cells and bone template communicate to ensure that limbs form correctly. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose mutations are linked to bone and joint pathologies. Here, we show the abundant expression of LRP1 in skeletal progenitor cells, especially in the perichondrium – the dense layer of fibrous connective tissue enveloping the cartilage of the developing limb bud. Our mouse models reveal that LRP1 deficiency in these stem cells (Lrp1flox/flox/Prrx1Cre) but not in chondrocytes (Lrp1flox/flox/AcanCreERT2) causes disrupted articulation and cavitation starting at as early as embryonic stage 16.5. LRP1 deficiency is also associated with aberrant accumulation of LRP1 ligands including tissue-inhibitor of metalloproteinase 3 and CCN2. These early abnormalities result in severe defects in multiple joints, plus markedly deformed and low-density long bones leading to dwarfism and impaired mobility. Ourin vitroexploration shows unique regulation of non-canonical WNT components by LRP1 that may explain the malformation of long bones. Mechanistically, we found that LRP1 facilitates cell-association, endocytic recycling but not degradation, and graded distribution of Wnt5a in the developing limbs. We propose that LRP1-mediated endocytic regulation of availability and distribution of extracellular signalling molecules play a critical role in limb development. This provides a novel mechanism for crosstalk among skeletal elements.
Beyond the (geometric) mean: stochastic models undermine deterministic predictions of bet hedger evolution
Authors: Weissman Maya , Raynes Yevgeniy , Weinreich Daniel
Published: July 2023

Bet hedging is a ubiquitous strategy for risk reduction in the face of unpredictable environmental change where a lineage lowers its variance in fitness across environments at the expense of also lowering its arithmetic mean fitness. Classically, the benefit of bet hedging has been quantified using geometric mean fitness (GMF); bet hedging is expected to evolve if and only if it has a higher GMF than the wild-type. We build upon previous research on the effect of incorporating stochasticity in phenotypic distribution, environment, and reproduction to investigate the extent to which these sources of stochasticity will impact the evolution of real-world bet hedging traits. We utilize both individual-based simulations and Markov chain numerics to demonstrate that modeling stochasticity can alter the sign of selection for the bet hedger compared to deterministic predictions. We find that bet hedging can be deleterious at small population sizes and beneficial at larger population sizes. This non-monotonic dependence of the sign of selection on population size, known as sign inversion, exists across parameter space for both conservative and diversified bet hedgers. We apply our model to published data of bet hedging strategies to show that sign inversion exists for biologically relevant parameters in two study systems:Papaver dubium, an annual poppy with variable germination phenology, andSalmonella typhimurium, a pathogenic bacteria that exhibits antibiotic persistence. Taken together, our results suggest that GMF is not enough to predict when bet hedging is adaptive.
Activation of the IKK2-NFκB pathway in VSMCs inhibits calcified vascular stiffness in CKD by reducing the secretion of calcifying extracellular vesicles
Authors: Miyazaki-Anzai Shinobu , Masuda Masashi , Keenan Audrey L. , Shiozaki Yuji , Miyazaki Makoto
Published: July 2023

IKK2-NFκB pathway mediated-inflammation in vascular smooth muscle cells (VSMCs) has been proposed to be an etiologic factor in medial calcification and stiffness. However, the role of the IKK2-NFκB pathway in medial calcification remains to be elucidated. In this study, we found that CKD induces inflammatory pathways through the local activation of the IKK2-NFκB pathway in VMSCs associated with calcified vascular stiffness. Despite reducing the expression of inflammatory mediators, complete inhibition of the IKK2-NFκB pathwayin vitroandin vivounexpectedly exacerbated vascular mineralization and stiffness. In contrast, activation of NFκB by SMC-specific IκB deficiency attenuated calcified vascular stiffness in CKD. Inhibition of the IKK2-NFκB pathway induced apoptosis of VSMCs by reducing anti-apoptotic gene expression, whereas activation of NFκB reduced CKD-dependent vascular cell death. In addition, increased calcifying extracellular vesicles through the inhibition of the IKK2-NFκB pathway induced mineralization of VSMCs, which was significantly reduced by blocking cell death. This study reveals that activation of the IKK2-NFκB pathway in VSMCs plays a protective role in CKD-dependent calcified vascular stiffness by reducing the release of apoptotic calcifying extracellular vesicles.
Associations of schooling type, qualification type, and subsequent health in mid-adulthood: Evidence from the 1970 British Cohort Study
Authors: Deng Keyao , Wright Liam , Silverwood Richard , Sullivan Alice , Bann David
Published: July 2023

Background

Education is thought to benefit subsequent health. However, existing studies have predominantly focused on educational attainment while the type of educational institution attended has been overlooked, despite being important indictors of education resource, quality, and influencing subsequent socioeconomic outcomes. In this study, we investigated associations between type of high school or university attended and multiple subsequent health outcomes in mid-adulthood.

Methods

Data from the 1970 British Cohort Study were used (N=8 107). Type of high school attended (comprehensive; grammar; private) was ascertained at age 16 and type of university (classified as higher (Russell Group) or normal-status) was reported at age 42. We investigated ten health measures that capture cardiometabolic risks, physical capabilities, and cognitive function measured at age 46. Multivariable regression models were used, adjusting for sex and childhood socioeconomic, health and cognitive factors.

Results

In unadjusted models, private school and higher-status university attendance were favourably associated with most health outcomes. After adjusting for potential confounders, associations between private school attendance and cardiometabolic risks remained; associations for higher-status university attendance and cognitive function remained, while the association with other health outcomes were largely attenuated. For example, private school attendance was associated with 0.14 standard deviation (SD) (95% confidence interval (CI): 0.04, 0.23) lower body mass index (BMI) while higher-status university attendance was associated with a 0.16 SD (0.07, 0.26) better performance in memory (word list recall task) compared with normal-status university attendance.

Conclusions

The type of educational institution attended was associated with multiple health outcomes—it could therefore be an important under-researched component of health inequalities. Further research is warranted to test the causal nature of this relationship and its generalisability to more recently born cohorts given changes in secondary education and the expansion of higher education.
PATIENT-ASSESSED QUALITY OF CARE AND LEVEL OF SATISFACTION IN HEALTHCARE FACILITIES IN CROSS RIVER STATE, NIGERIA
Authors: Etim John John , Nja Glory M. , Ejemot-Nwadiaro Regina Idu
Published: July 2023

Background

Patients’ experiences with health care professionals are a central component of quality of care, complementing more technical aspects of care such as the appropriate use of medications and procedures.

Aims

This study sought to assess patients’ quality of care and level of satisfaction in healthcare facilities in Cross River State, Nigeria.

Methods

The study adopted a descriptive cross sectional survey employing quantitative data collection method that utilized a semi-structured questionnaire to collect data from patients. A multi-stage sampling procedure was used where 405 respondents were selected through simple random sampling. A 27 items semi-structured questionnaire was used to elicit data from respondents. Data collected were analyzed and presented using descriptive statistics.

Results

On a multi response options, the study showed that more than half 294(72.8%) respondents were satisfied with the services provided by healthcare professionals on their current admission; more than half of the respondents 235(58.2%) were satisfied with previous care received; about half 197(48.8%) of the respondents complained about long waiting time to be seen on admission; more than half 209(51.7%) of the respondents strongly disagreed that the hospital/ward environment into which they were admitted was clean and conducive, with a significant proportion 335(82.9%) who were unable to get all the prescribed drugs from the facility, while just 69(17.2%) of those not satisfied could recall some instances/aspects of healthcare they were not satisfied with where 49(12.2%) recalled poor attitude of healthcare professionals.

Conclusions

Timely care and better communication between patient and healthcare providers were recommended among others.

What is already known on this topic

There is a recorded level of patients’ dissatisfaction with healthcare in the study setting.

What this study adds

Poor attitude of healthcare workers has been associated with patients’ dissatisfaction with healthcare.

Poor attitude of healthcare workers has been associated with poor work environment which by extension affect the mental health of healthcare staff.

How this study might affect research, practice or policy

This study outlines the implication of poor work environment on mental health of workers as by extension affects patients’ quality of care and as such calls better healthcare management by trained experts.
Injury incidence, severity and type across the menstrual cycle in elite female professional footballers: a prospective three season cohort study
Authors: Barlow Ally , Blodgett Joanna M , Williams Sean , Pedlar Charles R , Bruinvels Georgie
Published: July 2023

Objectives

The aim of the study was to assess the influence of menstrual cycle phase on injury incidence, severity and type in elite female professional footballers over three seasons.

Methods

Time-loss injuries and menstrual cycle data were prospectively recorded for 26 elite female football players across three seasons. The menstrual cycle was categorised into four phases using a standardised model: menstruation (phase 1; P1), remainder of follicular phase (phase 2; P2), early luteal (phase 3; P3), and pre-menstrual phase (phase 4; P4). Injury incidence rates (IRR) and ratios (IIRR) were calculated for overall injuries, injury type, contact vs non-contact, game/training and severity of injury.

Results

593 cycles across 13,390 days were tracked during the study and 74 injuries from 26 players were eligible for analysis. Muscle injuries were the most prevalent sub-type (n=41). When comparing IRR between phases (reference: P1), injury rates were highest in P4 for overall (IIRR: 2.30 [95% CI: 0.99-5.34; p=0.05]), muscle-specific (6.07 [1.34-27.43; p=0.02]), non-contact (3.05 [1.10-8.50; p=0.03]) and ≤7 day’s time-loss injuries (4.40 [0.93-20.76; p=0.06]). Muscle-specific (IIRR P3:P1: 5.07 [1.16-22.07; p=0.03]) and ≤7 day’s time-loss (4.47 [1.01-19.68; p=0.05]) injury risk were also significantly higher in P3. No anterior cruciate ligament injuries were recorded across the monitoring period.

Conclusion

Injury risk was significantly elevated during the luteal phase of the menstrual cycle (P3 and P4) among elite female professional footballers. Further research is urgently needed to better understand the influence of the menstrual cycle on injury risk and to develop interventions to mitigate risk.

What are the new findings?

Injury risk was lowest in phase 1, during menstruation.

Rate of overall injuries was highest in the luteal phase (phases 3 and 4), specifically for non-contact and lower severity injuries (e.g. 1-7 days missed training).

Muscle injury risk increased across the menstrual cycle, with a greater incidence in the luteal phase (phases 3 and 4).

Conversely to current perceptions, squad availability is significantly impacted by a wide range of injuries that are related to menstrual cycle phase, not just significant ligament injuries.

How might it impact on clinical practice in the near future?

When reviewing injury occurrence, mechanism and prevention guidelines, it is crucial to consider menstrual cycle day and phase.

Longitudinal menstrual cycle monitoring provides an additional, potentially useful factor to support female athletes.

The results of this study demonstrate that there is an urgent need to collect menstrual cycle data alongside standardised injury data to allow for further exploration in a larger sample.
Focal transcranial direct current stimulation of auditory cortex in chronic tinnitus: A randomized controlled mechanistic trial
Authors: Leaver Amber M. , Chen Yufen J. , Parrish Todd B.
Published: July 2023

Objective

The goal of this pilot MRI study was to understand how focal transcranial direct current stimulation (tDCS) targeting auditory cortex changes brain function in chronic tinnitus.

Methods

People with chronic tinnitus were randomized to active or sham tDCS on five consecutive days in this pilot mechanistic trial (n=10/group). Focal 4×1 tDCS (central anode, surround cathodes) targeted left auditory cortex, with single-blind 2mA current during twenty-minute sessions. Arterial spin-labeled and blood oxygenation level dependent MRI occurred immediately before and after the first tDCS session, and tinnitus symptoms were measured starting one week before the first tDCS session and through four weeks after the final session.

Results

Acute increases in cerebral blood flow and functional connectivity were noted in auditory cortex after the first active tDCS session. Reduced tinnitus loudness ratings after the final tDCS session correlated with acute change in functional connectivity between an auditory network and mediodorsal thalamus and prefrontal cortex. Reduced tinnitus intrusiveness also correlated with acute change in connectivity between precuneus and an auditory network.

Conclusions

Focal auditory-cortex tDCS can influence function in thalamus, auditory, and prefrontal cortex, which may associate with improved tinnitus.

Significance

With future refinement, noninvasive brain stimulation targeting auditory cortex could become a viable intervention for tinnitus.

HIGHLIGHTS

Focal transcranial direct current stimulation (tDCS) of auditory cortex changes cerebral blood flow and connectivity in tinnitus

Tinnitus loudness ratings decreased on average after five sessions of active focal tDCS

Acute changes in auditory, thalamic, and prefrontal function may predict quieter tinnitus after five sessions