bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐intensity resistance training and collagen supplementation improve patellar tendon adaptations in professional female soccer athletes
Authors: Lee Joonsung , Robshaw David C. , Erskine Robert M.
Published: August 2024

We investigated whether 10 weeks of pre‐season soccer training (including high‐intensity resistance exercise) with hydrolysed collagen (COL) supplementation would confer greater changes in patellar tendon (PT) mechanical and material properties compared with placebo (PLA) in professional female soccer athletes. Eleven athletes from the first team squad of a Football Association Women's Championship soccer club volunteered to participate in this study (age, 25.7 ± 4.2 years; height, 1.68 ± 0.04 m; mass, 64.0 ± 4.6 kg). Participants were pair‐matched for baseline knee extensor maximum isometric voluntary contraction torque, age, height and mass and were randomly assigned to the COL group (n = 6) or PLA group (n = 5). Participants were given 30 g COL or energy‐matched (36.5 g maltodextrin and 8.4 g fructose) PLA, plus 500 mg vitamin C before each training session, which consisted of high‐intensity lower‐limb resistance exercise, plyometric or pitch‐based exercise 3 days/week for 10 weeks during the pre‐season period. We assessed knee extensor maximum isometric voluntary contraction torque and PT properties using isokinetic dynamometry and ultrasonography before and after the intervention. The PT stiffness [COL, +15.4% ± 3.1% (d = 0.81) vs. PLA, +4.6% ± 3.0% (d = 0.32), P = 0.002] and Young's modulus [COL, +14.2% ± 4.0% (d = 0.65) vs. PLA, +3.4% ± 2.8% (d = 0.15), P = 0.004] increased more in COL than in PLA. There was a main effect of training on PT cross‐sectional area (P = 0.027), but no interaction effect (P = 0.934). To conclude, 10 weeks of pre‐season soccer training (incorporating high‐intensity resistance exercise) with 30 g COL increased PT stiffness and Young's modulus more than training alone in professional female soccer athletes. This has positive implications for improving athletic performance and mitigating injury risk.
A Buffer-Based Steel Production Scheduling Under Uncertain Environment
Authors: Morita Daisuke , Suwa Haruhiko
Published: August 2024

Scheduling in steel manufacturing is a difficult problem with various complex constraints and uncertainties. This study proposes a steel scheduling decision-making model involving time and resource buffers for raw material blending, casting, and rolling planning processes. The proposed model estimates suitable time and resource buffers allocated to the baseline schedule to absorb the operation delay. The numerical experiments clarify the critical properties of the considered scheduling problem and investigate the proposed approach from a macro perspective.
A Study on Hierarchical Production Planning Framework for Engineer-to-Order Production of Large Products
Authors: Iwamura Koji , Morinaga Eiji , Hirahara Yoshiyuki , Fukuda Masamitsu , Niinuma Ayumu , Oshima Hirotomo , Namioka Yasuo
Published: August 2024

Engineer-to-order (ETO) production is a method in which products are designed and manufactured in response to customer orders. Typical products of ETO production targeted in this study are large products such as power plants, plants, and shipbuilding. These products have long lead times and delivery times, and production plans need to be generated for a year or more in advance.

This study proposes a hierarchical production planning (HPP) framework to generate long-term, medium-term, and short-term production plans using common granularity of production equipment and unit time on production planning method for ETO production of large products. A load planning required for the long-term production plan is formulated as an integer programming problem, and the load plans are generated using a mathematical programming solver and a constraint programming solver.
Forced Chatter Sound in End-Milling Processes for Bamboo Fiber Extraction Using a Machining Center
Authors: Tanaka Kaito , Kitazaki Reo , Nakahara Yutaro , Nakagawa Masao , Hirogaki Toshiki , Aoyama Eiichi , Nobe Hiromichi
Published: August 2024

In this study, we attempted to fabricate a self-adhesive molded product made entirely of bamboo. The raw materials were bamboo tube chips cut using a machining center. The chips can be made parallel to the vascular bundles with adjustable dimensions. However, the vibration inherent in the working material during the cutting process could potentially affect the chip shape. Therefore, we evaluated the effect of workpiece-specific vibration on fiber shape. Additionally, cutting sound, which is considered highly correlated with workpiece vibration suppression, was examined. The results showed that the first- (x-parallel) and second-order (y-parallel) intrinsic vibrations decreased the mean fiber width and increased its standard deviation. Cutting sound was also evaluated. The correlation between cutting sound and vibration acceleration was high when the natural to intermittent cutting frequency ratio was an integer. Under other conditions, cutting sound peaks were observed at integer multiples of the intermittent cutting frequency, and the maximum peak occurred at the frequency closest to the natural frequency. Subsequently, a natural frequency calculation method using the cutting sound was proposed. When this equation was applied to actual cutting sounds, the natural frequency was predicted with high accuracy. The results indicate that the spindle speed could be set to avoid the workpiece natural vibration using the cutting sound.
Reaction Time Across the Menstrual Cycle: A Critically Appraised Topic
Authors: Marshall Kelsey A. , Chimera Nicole J.
Published: August 2024

Clinical Scenario: Reaction time is integral in many tasks during work, sport, and life, thus, alterations in reaction time may impact performance and injury risk. There are various factors that can influence reaction time, such as the physical state of the individual, including their age or sex. When comparing males and females, there is a major physiological difference to their physical state as hormones fluctuate during menstrual cycle phases, which not only affects the reproductive system, but females may experience physiological, cardiovascular, respiratory, or metabolic changes throughout their menstrual cycle phases. Therefore, this goal of this critically appraised topic is to examine whether reaction time changes during menstrual cycle phases. Focused Clinical Question: In healthy, eumenorrheic females, does reaction time change from one menstrual cycle phase to other menstrual cycle phases? Summary of Key Findings: Among the five studies evaluated in this CAT, all found significant changes to reaction time during phases of the menstrual cycle. Most studies found that reaction time was inversely related to sex hormone levels, indicating that phases with low hormone levels had longer reaction time than those phases with higher hormone levels; however, one study found reaction time to be prolonged or slower during the luteal phase, when hormone levels are higher. Clinical Bottom Line: Both auditory and visual reaction times vary across the menstrual cycle in healthy females with regular menstrual cycles (frequency and length). Given these findings, it is important to incorporate reaction time training across all phases of the menstrual cycle in female athletes. Strength of Clinical Recommendation: Based on the Strength of Recommendation Taxonomy, a Grade C is the strength of recommendation.
Estimating Muscle Fiber-Type Composition in Elite Athletes: A Survey on Current Practices and Perceived Merit
Authors: Lievens Eline , Van de Casteele Freek , De Block Fien , Van Vossel Kim , Vandenbogaerde Tom , Sandford Gareth N. , Bellinger Phillip , Minahan Clare , Bourgois Jan G. , Stellingwerff Trent , Mujika Iñigo , Derave Wim
Published: August 2024

Purpose: To gather information on practices and perceptions of high-performance experts regarding their athletes’ muscle fiber-type composition (MFTC) and its estimation. Methods: A questionnaire on the noninvasive versus invasive estimation of MFTC was completed by 446 experts including coaches and sport-science/sports-medicine staff. Moreover, the perceived importance of MFTC for training and performance optimization was assessed. Differences between sport types (individual and team sports) were analyzed using chi-square tests. Results: Forty percent of the experts implemented MFTC assessment in pursuit of performance optimization, while 50% did not know their athletes’ MFTC but expressed a desire to implement it if they would be able to assess MFTC. Ten percent did not perceive value in MFTC assessment. Only 18% of experts believed that their athletes would undergo a muscle biopsy, leading to the adoption of alternative noninvasive techniques. Experts primarily relied on their experience to estimate MFTC (65%), with experts working in individual sports using their experience more frequently than those working in team sports (68% vs 51%; P = .009). Jump tests emerged as the second-most commonly employed method for estimating MFTC (56%). When only considering experts who are currently using MFTC, 87% use MFTC to individualize training volume and 84% to individualize training intensity. Conclusions: Experts value MFTC assessment primarily to individualize training but mainly rely on noninvasive methods to estimate MFTC. Some of these methods lack scientific validity, suggesting a continuing need for education and further research in this area.
Role of Thigh Muscle Strength and Joint Kinematics in Dynamic Stability: Implications for Y-Balance Test Performance
Authors: Turner Jeffrey A. , Hartshorne Matthew L. , Padua Darin A.
Published: August 2024

Context: The Y-Balance Test Lower Quarter (YBT-LQ) is a widely utilized tool for evaluating dynamic postural control, requiring a combination of mobility and strength. This study aimed to investigate the combined relationship between isometric thigh muscle strength and joint kinematics on YBT-LQ performance. Design: Cross-sectional laboratory study. Methods: Isometric quadriceps and hamstrings strength were measured before the YBT-LQ in 39 healthy participants (27 females and 12 males). The test was performed under 3-dimensional markerless motion capture, where joint kinematics were extracted from the maximum reach position from each direction. Three multivariable linear regression models were then used to determine the strongest combination of predictors for YBT-LQ performance. Results: Greater hamstrings strength and increased knee flexion, ankle dorsiflexion, and trunk ipsilateral-flexion joint angles explained 56.8% (P < .001) of the variance in anterior reach. Hip flexion, knee flexion, and ankle dorsiflexion angles were the strongest predictors for posteromedial reach distance, explaining 73.0% of the variance (P < .001). Last, 43.3% (P < .001) of the variance in posterolateral reach distance was predicted by hamstring strength and knee-flexion angle. Conclusions: These results emphasize the importance of hamstring strength in YBT-LQ performance across different reach directions. Additionally, the kinematics illustrate a potential movement strategy for maximizing reach distance on the YBT-LQ in healthy individuals. Clinicians can utilize this information to guide interventions aimed at improving dynamic postural control, particularly by focusing on increasing hamstring strength and testing for impairments in specific movement patterns.
Development and Validation of the Teacher Motivation in Physical Education Questionnaire
Authors: Garn Alex C. , Simonton Jr Kelly L. , Mercier Kevin
Published: August 2024

Purpose: Grounded in the expectancy-value theory framework, the purpose of this study was to develop and identify the psychometric properties of the Teaching Motivation in Physical Education Questionnaire. Methods: The process included testing content validity with experts (n = 16), construct validity and measurement invariance using factor analysis, and convergent validity using structural equation modeling (SEM) in two physical education teacher samples (n = 373; n = 400). Results: Factor analysis identified a 17-item questionnaire measuring teachers’ expectancy, value, and cost beliefs. Measurement invariance testing revealed equivalence between male and female as well as primary and secondary physical education teachers. Correlational and structural equation modeling analyses showed the adaptive nature of expectancy and subjective task value beliefs along with the maladaptive nature of cost beliefs. Discussion/Conclusion: The Teaching Motivation in Physical Education Questionnaire provides a theoretically grounded approach to investigate physical education teachers’ motivation toward curriculum and instruction.
Is Biobanding the Future of Youth Sport Participation?
Authors: Chimera Nicole J. , Falk Bareket , Klentrou Panagiota , Sullivan Phillip
Published: August 2024

Traditionally, sports participation has been based on the chronological age of the individual with year of birth determining participation grouping. However, grouping by chronological age can result in individuals who are nearly a full year different in age competing within the same age group. Moreover, during the pubertal years, age grouping may provide physical (size) advantage to early maturers and disadvantage to late maturers. These advantages/disadvantages could impact talent selection, psychosocial aspects of sport participation, technical and tactical skill development, competitiveness, and injury risk. Biobanding is an alternative method for determining sport participation categorization and uses factors of growth and/or maturation, rather than traditional chronological age, for grouping athletes. Implementation of biobanding in sports may be advantageous to both early and late-maturing athlete development.
Polyolefin waste to light olefins with ethylene and base-metal heterogeneous catalysts
Authors: Conk Richard J. , Stahler Jules F. , Shi Jake X. , Yang Ji , Lefton Natalie G. , Brunn John N. , Bell Alexis T. , Hartwig John F.
Published: August 2024

The selective conversion of polyethylene (PE), polypropylene (PP), and mixtures of these two polymers to form products with high volume demand is urgently needed because current methods suffer from low selectivity, produce large quantities of greenhouse gases, or rely on expensive, single-use catalysts. The isomerizing ethenolysis of unsaturated polyolefins could be an energetically and environmentally viable route to propylene and isobutylene; however, noble-metal homogeneous catalysts and an unsaturated polyolefin are currently required and the process has been limited to PE. We show that the simple combination of tungsten oxide on silica and sodium on gamma-alumina transforms PE, PP, or a mixture of the two, including postconsumer forms of these materials, to propylene or a mixture of propylene and isobutylene in greater than 90% yield at 320°C without the need for dehydrogenation of the starting polyolefins.
Opioid circuit opens path to pain relief
Authors: De Preter Caitlynn C. , Heinricher Mary M.
Published: August 2024

Manipulation of neural circuits targeted by morphine enables pain relief without opioids
How the Three Sisters shrug off pests
Authors: Pennisi Elizabeth
Published: August 2024

Crops such as maize, beans, and squash can team up, but the mix matters
Ancient monument’s builders knew their science
Authors: Richter Hannah
Published: August 2024

Building a Spanish megalith required sophisticated physics, geometry, and geology
Efficacy of ensitrelvir for cough due to COVID-19 Omicron variant in medical healthcare workers
Authors: Miyashita Naoyuki , Nakamori Yasushi , Ogata Makoto , Fukuda Naoki , Yamura Akihisa , Ito Tomoki
Published: August 2024

We evaluated the efficacy of ensitrelvir for the treatment of cough due to coronavirus disease 2019 Omicron variant in medical healthcare workers. A total of 633 patients were registered in this study: 206 patients chose ensitrelvir and 427 patients chose symptomatic treatment. Difference in score changes using the Leicester Cough Questionnaire between groups was 3.17 on day 4, 3.24 on day 7, and 2.46 on day 14. The analysis demonstrated a significant difference at all time points.
A nanobody interaction with SARS-COV-2 Spike allows the versatile targeting of lentivirus vectors
Authors: Alfadhli Ayna , Bates Timothy A. , Barklis Robin Lid , Romanaggi CeAnn , Tafesse Fikadu G. , Barklis Eric
Published: August 2024

While investigating methods to target gene delivery vectors to specific cell types, we examined the potential of using a nanobody against the SARS-CoV-2 Spike protein receptor-binding domain to direct lentivirus infection of Spike-expressing cells. Using four different approaches, we found that lentiviruses with surface-exposed nanobody domains selectively infect Spike-expressing cells. Targeting is dependent on the fusion function of the Spike protein, and conforms to a model in which nanobody binding to the Spike protein triggers the Spike fusion machinery. The nanobody–Spike interaction also is capable of directing cell–cell fusion and the selective infection of nanobody-expressing cells by Spike-pseudotyped lentivirus vectors. Significantly, cells infected with SARS-CoV-2 are efficiently and selectively infected by lentivirus vectors pseudotyped with a chimeric nanobody protein. Our results suggest that cells infected by any virus that forms syncytia may be targeted for gene delivery by using an appropriate nanobody or virus receptor mimic. Vectors modified in this fashion may prove useful in the delivery of immunomodulators to infected foci to mitigate the effects of viral infections.

IMPORTANCE

We have discovered that lentiviruses decorated on their surfaces with a nanobody against the SARS-CoV-2 Spike protein selectively infect Spike-expressing cells. Infection is dependent on the specificity of the nanobody and the fusion function of the Spike protein and conforms to a reverse fusion model, in which nanobody binding to Spike triggers the Spike fusion machinery. The nanobody–Spike interaction also can drive cell–cell fusion and infection of nanobody-expressing cells with viruses carrying the Spike protein. Importantly, cells infected with SARS-CoV-2 are selectively infected with nanobody-decorated lentiviruses. These results suggest that cells infected by any virus that expresses an active receptor-binding fusion protein may be targeted by vectors for delivery of cargoes to mitigate infections.
Infiltrating monocytes drive cardiac dysfunction in a cardiomyocyte-restricted mouse model of SARS-CoV-2 infection
Authors: Dmytrenko Oleksandr , Das Shibali , Kovacs Attila , Cicka Markus , Liu Meizi , Scheaffer Suzanne M. , Bredemeyer Andrea , Mack Matthias , Diamond Michael S. , Lavine Kory J.
Published: August 2024

Cardiovascular manifestations of coronavirus disease 2019 (COVID-19) include myocardial injury, heart failure, and myocarditis and are associated with long-term disability and mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antigens are found in the myocardium of COVID-19 patients, and human cardiomyocytes are susceptible to infection in cell or organoid cultures. While these observations raise the possibility that cardiomyocyte infection may contribute to the cardiac sequelae of COVID-19, a causal relationship between cardiomyocyte infection and myocardial dysfunction and pathology has not been established. Here, we generated a mouse model of cardiomyocyte-restricted infection by selectively expressing human angiotensin-converting enzyme 2 (hACE2), the SARS-CoV-2 receptor, in cardiomyocytes. Inoculation of
Myh6-Cre Rosa26
loxP-STOP-loxP-hACE2
mice with an ancestral, non-mouse-adapted strain of SARS-CoV-2 resulted in viral replication within the heart, accumulation of macrophages, and moderate left ventricular (LV) systolic dysfunction. Cardiac pathology in this model was transient and resolved with viral clearance. Blockade of monocyte trafficking reduced macrophage accumulation, suppressed the development of LV systolic dysfunction, and promoted viral clearance in the heart. These findings establish a mouse model of SARS-CoV-2 cardiomyocyte infection that recapitulates features of cardiac dysfunctions of COVID-19 and suggests that both viral replication and resultant innate immune responses contribute to cardiac pathology.

IMPORTANCE

Heart involvement after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection occurs in multiple ways and is associated with worse outcomes in coronavirus disease 2019 (COVID-19) patients. It remains unclear if cardiac disease is driven by primary infection of the heart or immune response to the virus. SARS-CoV-2 is capable of entering contractile cells of the heart in a culture dish. However, it remains unclear how such infection affects the function of the heart in the body. Here, we designed a mouse in which only heart muscle cells can be infected with a SARS-CoV-2 strain to study cardiac infection in isolation from other organ systems. In our model, infected mice show viral infection, worse function, and accumulation of immune cells in the heart. A subset of immune cells facilitates such worsening heart function. As this model shows features similar to those observed in patients, it may be useful for understanding the heart disease that occurs as a part of COVID-19.
The role of lipids in regulating macrophage antifungal immunity
Authors: Rouvray Sophie , Drummond Rebecca A.
Published: August 2024

Macrophages are critical components of the antifungal immune response. Disturbance in the number or function of these innate immune cells can significantly increase susceptibility to invasive fungal infections. Pathogenic fungi cause billions of infections every year and have an unmet clinical need, with many infections associated with unacceptably high mortality rates that primarily affect vulnerable patients with underlying immune defects. Lipid metabolism has been increasingly appreciated to significantly influence macrophage function, particularly of macrophages residing in lipid-rich organs, such as the brain, or macrophages specialized at clearing dead cells including alveolar macrophages in the lungs. In this review, we provide an overview of macrophage lipid metabolism, and discuss how lipid recycling and dysregulation affect key macrophage functions relevant for antifungal immunity including phagocytosis, functional polarization, and inflammasome activation. We focus on the fungal pathogen
Cryptococcus neoformans
, as this is the most common cause of death from fungal infection in humans and because several lines of evidence have already linked lipid metabolism in the regulation of
C. neoformans
and macrophage interactions.
Host-associated microbes mitigate the negative impacts of aquatic pollution
Authors: Diner Rachel E. , Allard Sarah M. , Gilbert Jack A.
Published: August 2024

Pollution can negatively impact aquatic ecosystems, aquaculture operations, and recreational water quality. Many aquatic microbes can sequester or degrade pollutants and have been utilized for bioremediation. While planktonic and benthic microbes are well-studied, host-associated microbes likely play an important role in mitigating the negative impacts of aquatic pollution and represent an unrealized source of microbial potential. For example, aquatic organisms that thrive in highly polluted environments or concentrate pollutants may have microbiomes adapted to these selective pressures. Understanding microbe–pollutant interactions in sensitive and valuable species could help protect human well-being and improve ecosystem resilience. Investigating these interactions using appropriate experimental systems and overcoming methodological challenges will present novel opportunities to protect and improve aquatic systems. In this perspective, we review examples of how microbes could mitigate negative impacts of aquatic pollution, outline target study systems, discuss challenges of advancing this field, and outline implications in the face of global changes.
Influence of stage and age on survival of patients with vulvar cancer in Germany: a retrospective study
Authors: Mack Luisa Carlotta , Hagemeier Anna , Forner Dirk Michael
Published: August 2024

Objectives

To evaluate the 5-year survival rate of patients with vulvar cancer, taking into account prognostic factors (International Federation of Gynecology and Obstetrics (FIGO) stage and age) and the influence of lymph node involvement and tumour size as well as the correlation between FIGO stage and age at onset.

Design

Retrospective cohort study.

Setting

German cancer registries.

Participants

The study included 17 017 patients diagnosed with vulvar cancer between 2004 and 2014 with follow-up until 2017. Exclusion criteria were incomplete documentation, age<18 years and death certificate only.

Primary and secondary outcome measures

The primary outcome was overall and relative survival according to FIGO stage and age and the distribution of FIGO stages by age group. Secondary outcomes analysed were tumour size and lymph node status as risk factors for mortality.

Results

The median age at diagnosis was 70 years. The overall 5-year survival rate was 69.5% (95% CI: 68.7% to 70.3%). The 5-year relative survival rates ranged from 91.9% (95% CI: 90.5% to 93.3%) to 21.3% (95% CI: 15.6% to 27.0%) for FIGO I to FIGO IVB and from 89.2% (95% CI: 87.6% to 90.8%) to 68.0% (95% CI: 65.3% to 70.7%) for age groups <55 to >75 years. Younger patients were significantly more often diagnosed with a low FIGO stage (p<0.001). Lymph node status and tumour size were independent factors influencing survival (HR: 1.79 (95% CI: 1.73 to 1.84; p<0.001) and 1.88 (95% CI: 1.80 to 1.96); p<0.001, respectively). The median follow-up time was 57 months.

Conclusion

Notably, the steepest decline in survival occurred within the first 3 years after diagnosis. Patients with the highest FIGO stages and those in the oldest age group had the worst survival rates. Furthermore, patients in the oldest age group were more likely to be diagnosed at higher stages. Lymph node status and tumour size were additional independent prognostic factors for mortality.
High-exchange ULTrafiltration to enhance recovery after paediatric cardiac surgery (ULTRA): study protocol for a Canadian double-blinded randomised controlled trial
Authors: Bierer Joel , Stanzel Roger , Henderson Mark , Krmpotic Kristina , Andreou Pantelis , Marshall Jean S. , Sapp John , Horne David
Published: August 2024

Introduction

Surgical repair is the standard of care for most infants and children with congenital heart disease. Cardiopulmonary bypass (CPB) is required to facilitate these operations but elicits a systemic inflammatory response, leading to postoperative organ dysfunction, morbidity and prolonged recovery after the surgery. Subzero-balance ultrafiltration (SBUF) has been shown to extract proinflammatory cytokines continuously throughout the CPB exposure. We hypothesize that a high-exchange SBUF (H-SBUF) will have a clinically relevant anti-inflammatory effect compared with a low-exchange SBUF (L-SBUF).

Methods and analysis

The ULTrafiltration to enhance Recovery After paediatric cardiac surgery (ULTRA) trial is a randomised, double-blind, parallel-group randomised trial conducted in a single paediatric cardiac surgery centre. Ninety-six patients less than 15 kg undergoing cardiac surgery with CPB will be randomly assigned to H-SBUF during CPB or L-SBUF during CPB in a 1:1 ratio with stratification by The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) score 1 and STAT score 2–5. The primary outcome is peak postoperative vasoactive-ventilation-renal score. Time series and peak values of vasoactive-ventilation renal score, vasoactive-inotrope score, ventilation index and oxygenation index will be collected. Secondary clinical outcomes include acute kidney injury, ventilator-free days, inotrope-free days, low cardiac output syndrome, mechanical circulatory support, intensive care unit length of stay and operative mortality. Secondary biomarker data include cytokine, chemokine and complement factor concentrations at baseline before CPB, at the end of CPB exposure and 24 hours following CPB. Analyses will be conducted on an intention-to-treat principle.

Ethics and dissemination

The study has ethics approval (#1024932 dated August 31, 2021) and enrolment commenced in September 2021. The primary manuscript and any subsequent analyses will be submitted for peer-reviewed publication.

Trial registration number

NCT04920643.
Drug providers’ perspectives on antibiotic misuse practices in eastern Ethiopia: a qualitative study
Authors: Edessa Dumessa , Kumsa Fekede Asefa , Dinsa Girmaye , Oljira Lemessa
Published: August 2024

Objective

Antibiotic misuse includes using them to treat colds and influenza, obtaining them without a prescription, not finishing the prescribed course and sharing them with others. Although drug providers are well positioned to advise clients on proper stewardship practices, antibiotic misuse continues to rise in Ethiopia. It necessitates an understanding of why drug providers failed to limit such risky behaviours. This study aimed to explore drug providers’ perspectives on antibiotic misuse practices in eastern Ethiopia.

Setting

The study was conducted in rural Haramaya district and Harar town, eastern Ethiopia.

Design and participants

An exploratory qualitative study was undertaken between March and June 2023, among the 15 drug providers. In-depth interviews were conducted using pilot-tested, semistructured questions. The interviews were transcribed verbatim, translated into English and analysed thematically. The analyses considered the entire dataset and field notes.

Results

The study identified self-medication pressures, non-prescribed dispensing motives, insufficient regulatory functions and a lack of specific antibiotic use policy as the key contributors to antibiotic misuse. We found previous usage experience, a desire to avoid extra costs and a lack of essential diagnostics and antibiotics in public institutions as the key drivers of non-prescribed antibiotic access from private drug suppliers. Non-prescribed antibiotic dispensing in pharmacies was driven by client satisfaction, financial gain, business survival and market competition from informal sellers. Antibiotic misuse in the setting has also been linked to traditional and ineffective dispensing audits, inadequate regulatory oversights and policy gaps.

Conclusion

This study highlights profits and oversimplified access to antibiotics as the main motivations for their misuse. It also identifies the traditional antibiotic dispensing audit as an inefficient regulatory operation. Hence, enforcing specific antibiotic usage policy guidance that entails an automated practice audit, a responsible office and insurance coverage for persons with financial limitations can help optimise antibiotic use while reducing resistance consequences.
Patient pathways for four major chronic respiratory diseases in England between 2008 and 2021
Authors: Ioannides Anne E , Morgan Ann D , Quint Jennifer K
Published: August 2024

Background

Not all chronic diseases have clear pathways and time targets for diagnosis. We explored pathways and timings for four major chronic respiratory diseases in England.

Methods

Using deidentified electronic healthcare records from Clinical Practice Research Datalink Aurum linked to Hospital Episode Statistics, we derived cohorts of patients diagnosed with asthma, chronic obstructive pulmonary disease (COPD), ILD or bronchiectasis at three time periods (2008/2009, 2018/2019 and 2020/2021). We followed people 2 years before and 2 years after diagnosis, calculating the proportion of people who presented with symptoms, underwent diagnostic tests, were treated and consulted healthcare (primary or secondary) and calculated time intervals between events. We repeated analyses by socioeconomic status and geographical region.

Results

We descriptively studied patient pathways for 429 619 individuals across all time frames and diseases. Most people (>87%) had first evidence of diagnosis in primary care. The proportion of people reporting symptoms prior to diagnosis was similar for asthma, COPD and ILD (41.0%–57.9%) and higher in bronchiectasis (67.9%–71.8%). The proportion undergoing diagnostic tests was high for COPD and bronchiectasis (77.6%–89.2%) and lower for asthma (14%–32.7%) and ILD (2.6%–3.3%). The proportion of people undergoing diagnostic tests decreased in 2020/2021 for all diseases, mostly COPD. Time (months) (median (IQR)) between symptoms and diagnosis, averaged over three time periods, was lowest in asthma (~7.5 (1.3–16.0)), followed by COPD (~8.6 (1.8–17.2)), ILD (~10.1 (3.6–18.0)) and bronchiectasis (~13.5 (5.9–19.8)). Time from symptoms to diagnosis increased by ~2 months in asthma and COPD over the three time periods. Although most patients were symptomatically treated prior to diagnosis, time between diagnosis and postdiagnostic treatment was around 4 months for ILD, 3 months for bronchiectasis and instantaneous for asthma and COPD. Socioeconomic status and regional trends showed little disparity.

Conclusion

Current pathways demonstrate missed opportunities to diagnose and manage disease and to improve disease coding.
Physical activity modification over time according to socioeconomic position: results from the EPIC-Italy cohort study
Authors: Franco Matteo , Facchini Luigi , Sacerdote Carlotta , Masala Giovanna , Manfredi Luca , Dansero Lucia , Bendinelli Benedetta , Assedi Melania , Vitale Valentina , Pala Valeria , Caini Saverio , Ricceri Fulvio
Published: August 2024

Objectives

Our study aimed to investigate how physical activity (PA) changes over an 11-year follow-up among adults from different socioeconomic positions (SEP) near retirement age. Moreover, an analysis of different PA types is considered.

Methods

We used data from the EPIC-Italy cohort. We evaluated PA using the Cambridge Physical Activity Index (CPAI) and the metabolic equivalent of tasks (MET) per hour of activity for recreational PA and household PA. Educational level was assessed using the Relative Index of Inequality (RII). Occupational classes were classified according to LIFEPATH Consortium knowledge. Logistic regression was used to analyse PA among SEP and changes during follow-up. Analyses were also conducted separately for sex.

Results

The higher educated were more prevalent in the higher quartile of recreational PA than the lower educated both at baseline and follow-up (37% vs 28% and 37% vs 27%, respectively). At the baseline, the lower educated had a higher risk of being physically inactive than the higher educated based on recreational PA (overall OR: 1.50, 95% CI 1.40 to 1.60). Manual workers did not show a higher risk of less PA than professionals/managers (overall OR: 1.03, 95% CI 0.91 to 1.16).

At follow-up, the lower educated and manual workers showed a higher risk of being physically inactive (lower educated OR: 1.46, 95% CI 1.37 to 1.56; manual worker OR: 1.33, 95% CI 1.18 to 1.50). The analyses of changes in PA showed that those who were less educated or manual workers had a higher risk of worsening their PA during the follow-up period, particularly women in recreational PA and men in CPAI measurement.

Conclusion

Individuals who had a disadvantaged SEP showed a higher risk of performing less PA over time.
Prevalence of electrocardiographic markers associated with myocardial fibrosis in masters athletes: a cohort study
Authors: Kramer Tilmann , Ventovuori Ville , Heinonen Ari , Parkkari Jari , Korhonen Marko T , Rovio Anja , Hoenemann Jan-Niklas , Möstl Stefan , Sies Wolfram , Kaiser-Stolz Claudia , Chilibeck Philip , Tanaka Hirofumi , Kramer Mira , Rittweger Joern , Hautala Arto J
Published: August 2024

Objectives

Myocardial fibrosis (MF) is associated with an increased predisposition to adverse cardiac events. The accumulation of high-volume and high-intensity exercise over an extended duration potentially increases the risk of MF. Specific electrocardiographic markers have been correlated with the presence of MF. This study assessed the prevalence of MF-related electrocardiographic markers in a Track and Field Master Athletics Cohort (TaFMAC).

Methods

Twelve-lead resting electrocardiograms (ECGs) were conducted on 155 athletes (90 males and 65 females) participating in the World Masters Athletics 2022. The ECG markers associated with MF, including pathological Q waves, inverted T waves, fragmented QRS complex, and prolonged QRS complex, were compared among different athletic specialities (endurance athletes n=51, sprinters n=69 and strength and power n=35).

Results

Overall, 71 instances of MF-related markers were identified from 155 ECG recordings (46%). Fragmented QRS emerged as the most common marker, with a prevalence of 29% in endurance and strength and power athletes, and 35% in sprinters. No significant group differences were observed in the prevalence of MF markers, whether analysed collectively (p=0.467) or individually (pathological Q waves p=0.367, inverted T waves p=0.309, fragmented QRS complex p=0.747 and prolonged QRS complex p=0.132).

Conclusions

The prevalence of MF markers, as determined by resting ECG, was evident in nearly half of masters athletes, irrespective of sex and sporting specialisation. These findings suggest resting ECG as a promising non-invasive method for the early identification of MF in athlete’s hearts.
Socioeconomic status across the early life course predicts gene expression signatures of disease and senescence
Authors: Potente Cecilia , Bodelet Julien , Himeri Hira , Cole Steve , Harris Kathleen , Shanahan Michael
Published: August 2024

Background

Socioeconomic status (SES) is associated with many chronic diseases, indicators of senescence and mortality. However, the changing salience of SES in the prediction of adult health is not well understood. Using mRNA-seq abundance data from wave V of the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examine the extent to which SES across the early life course is related to gene expression-based signatures for chronic diseases, senescence and inflammation in the late 30s.

Methods

We use Bayesian methods to identify the most likely model of life course epidemiology (critical, sensitive and accumulation models) that characterises the changing importance of parental SES and SES during young (ages 27–30) and mid-adulthood (ages 36–39) in the prediction of the signatures.

Results

For most signatures, SES is an important predictor in all periods, although parental SES or SES during young adulthood are often the most predictive. For three signatures (components of diabetes, inflammation and ageing), critical period models involving the exclusive salience of SES in young adulthood (for diabetes) or parental SES (for inflammation and ageing) are most probable. The observed associations are likely mediated by body mass index.

Conclusion

Models of life course patterns of SES may inform efforts to identify age-specific mechanisms by which SES is associated with health at different points in life and they also suggest an enhanced approach to prediction models that recognise the changing salience of risk factors.
Nivolumab maintenance improves overall survival of patients with advanced melanoma who experience severe immune-related adverse events on nivolumab plus ipilimumab
Authors: Maloney Anna K , Giobbie-Hurder Anita , Katukota Nikita , Fogarasi Miklos C , Ott Patrick A , Hodi F Stephen , Sussman Tamara A , Silk Ann W , Haq Rizwan , Liu David , Insco Megan , Buchbinder Elizabeth I
Published: August 2024

Background

The combination of ipilimumab and nivolumab is a highly effective treatment for metastatic cutaneous melanoma. However, immune-related adverse events (irAEs) are common, often necessitating treatment interruption and the use of immunosuppressive agents. There is no data on the impact of resuming nivolumab on survival following recovery from the irAE and completion of immunosuppressive treatment.

Patients and methods

In this retrospective analysis, we examined a cohort of patients treated with ipilimumab/nivolumab who developed irAEs requiring treatment interruption and immunosuppressive therapy. The differences in physician practice patterns at our institution allowed us to examine the survival effect of restarting single-agent nivolumab. A multivariate analysis of clinical factors associated with improved survival was performed.

Results

We identified 165 patients who were treated with ipilimumab/nivolumab and developed irAEs requiring treatment interruption and immunosuppressive therapy. Patients with the best overall response of progressive disease were excluded. Of the remaining 122 patients, 46 resumed single-agent nivolumab. When stratified by age and adjusted for sex, M-stage, lactate dehydrogenase (LDH), therapy duration, and irAE type, the effect of resumption of nivolumab on survival was highly significant (p=0.02). Patients who resumed nivolumab had a 68% reduction in the hazard of death compared with patients who had not yet or never resumed nivolumab (HR: 0.32, 95% CI: 0.12 to 0.84). Of the patients who resumed nivolumab, 12 (26%) patients had subsequent irAEs, with five patients having grade 3 irAEs. No grade 4 or 5 irAEs were noted.

Conclusions

Resuming single-agent nivolumab following a treatment interruption for ipilimumab/nivolumab-associated irAE and completion of immunosuppressive therapy increased overall survival compared with discontinuing nivolumab permanently in patients with metastatic melanoma. Toxicity observed post-resumption of single-agent nivolumab was manageable with no severe irAEs observed.
Immune checkpoint blockade: timing is everything
Authors: Sinicrope Frank A , Turk Mary Jo
Published: August 2024

Neoadjuvant immunotherapy effectively uses the in situ tumor as a reservoir of tumor antigens to promote systemic antitumor immunity. Studies indicate that intratumoral responses to immune checkpoint inhibitors (ICIs) are mediated by resident memory T cells cells that are sequestered in tumors and have specificity for a wide range oftumor antigens. ICI treatment produces de novo priming of CD8+T cells in tumor and in tumor-draining lymph nodes, and can boost the antitumor immune response by blocking inhibitory checkpoint proteins that can turn off T cells within the tumor. Neoadjuvant ICI treatment can enhance both intratumoral and systemic antitumor immunity, including expansion of intratumoral T-cell clones which is strongly associated with pathological treatment response. Recent data have shown high rates of pathological response to neoadjuvant immunotherapy with prolongation of survival compared with adjuvant ICI therapy alone in patients with unresectable or advanced melanoma. These data suggest that removal of the reservoir of tumor-specific T cells in the tumor and draining nodes by surgical resection may remove a significant proportion of the patient’s antitumor immunity with the potential to compromise ICI outcomes.
Exploratory analysis of the potential disconnect between objective inflammatory response and clinical response following certolizumab pegol treatment in patients with active axial spondyloarthritis
Authors: Rudwaleit Martin , Marzo-Ortega Helena , Navarro-Compán Victoria , Tham Rachel , Kumke Thomas , Bauer Lars , de Peyrecave Natasha , Kim Mindy , Van den Bosch Filip
Published: August 2024

Introduction

This post hoc analysis evaluated the relationship between objective measures of inflammation and clinical outcomes following 12 weeks of certolizumab pegol (CZP) treatment in patients with active axial spondyloarthritis (axSpA).

Methods

We report the proportion of patients achieving ≥50% and ≥75% improvements in clinical composite outcome measures of disease activity (Axial Spondyloarthritis Disease Activity Score [ASDAS], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) and objective measures of inflammation (C reactive protein [CRP], Ankylosing Spondylitis spine MRI score [ASspiMRI-a] Berlin score and Spondyloarthritis Research Consortium of Canada [SPARCC] MRI Sacroiliac Joints [SIJ] score) following 12 weeks of CZP treatment. Data from two independent readers over four MRI reading campaigns were pooled using a mixed model with repeated measures for each variable.

Results

136 patients (radiographic axSpA [r-axSpA]: 76; non-radiographic axSpA [nr-axSpA]: 60) were included. Following CZP treatment, CRP, ASspiMRI-a Berlin score and SPARCC SIJ score were reduced by ≥50% in most patients (CRP: 136/136 [100.0%]; Berlin: 73/136 [53.7%]; SPARCC SIJ: 71/136 [52.2%]), and often by ≥75%. Less than half of patients with r-axSpA and nr-axSpA showed ≥50% reduction in clinical responses (BASDAI: 64/136 [47.1%]; ASDAS: 66/136 [48.5%]). These results were also observed at the individual patient level; ≥50% improvements in MRI/CRP inflammatory measures did not translate into similar improvements in clinical responses for most patients.

Conclusion

There is a potential disconnect between objective measures of inflammation and clinical outcome responses in patients with axSpA. The use of only clinical response measures as trial endpoints may underestimate anti-inflammatory treatment effects.

Trial registration number

NCT01087762.
Model-independent reconstruction of f(T) and f(R) gravity
Authors: Han Yufen , Li En-Kun , Xu Lixin
Published: August 2024

In this paper, we revisit the model-independent reconstruction of f(T) and f(R) gravity at the cosmological background and linear matter density perturbation levels respectively via Gaussian process by using the currently available cosmic observations, which consist Pantheon+ SNe Ia samples, observed Hubble parameter H(z) and the redshift space distortion $$f\sigma _8(z)$$

f

σ
8

(
z
)

data points. For the f(T) gravity, we find the reconstructed form of f(T) from the background and perturbation levels cannot match each other well in 1$$\sigma $$
σ
regions, it might imply the tension between the background and perturbation evolutions. For the f(R) gravity, due to the existence of an extra degree for freedom $${\dot{F}}$$

F
˙

, the form of f(R) can be reconstructed by the addition of the growth rate function. The results show that the reconstructed form of f(R) might be viable in the redshift range of $$z<0.75$$

z
<
0.75

based on the currently available cosmic observations, for filling the requirement of $$f_{,R}>0$$

f

,
R

>
0

and $$f_{,RR}>0$$

f

,
R
R

>
0

to avoid a tachyonic instability and be ghosts free in theory.
Chaotic Grid-Scroll Attractors and Multistability in a Pair of Mutually Coupled Third-Order Systems
Authors: Mekak-Egong Hermann-Dior , Ramadoss Janarthanan , Kengne Jacques , Karthikeyan Anitha
Published: August 2024

This research delves into simple Jerk-type dynamical networks, constructed using a specific bidirectional coupling scheme that influences the sub-oscillators and compound nonlinearity gradient functions that perturb each sub-unit of the network. The novelty of this work is to demonstrate a new pedagogical method able to stimulate the formation of higher-order multiscroll dynamics in the Jerk sub-oscillator. This is done by modeling a simple dynamic network built by applying a special bidirectional coupling between the Jerk sub-systems. Another novelty of this approach is that it allows us to study the collective dynamics of Jerk system networks, which has not yet been done in the literature. Multiscroll systems are exceedingly complex dynamically, making them valuable in chaos-based applications. The pedagogical approach used in this study is exceptional because it produces many additional equilibrium points (from 5 to 25 in dynamical network 1, and from 3 to 15 in dynamical network 2) in each Jerk sub-unit of the network. These equilibria elevate the complexity of Jerk systems by emulating higher-order multiscroll dynamics. The methodology used in this study is efficient and differs from those used in the literature, which mainly uses nonlinear multizero functions in dissipative systems. This research further explores the dynamic system characterization tools and conducts an experimental investigation on a microcontroller (ATMEGA2560) to confirm the predictions.