bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforaminal posterior lumbar interbody fusion microscopic safe operating area: a three-dimensional model study based on computed tomography imaging
Authors: Wang Wei , Cui Yukai , Sun Xiaohao , Zhang Haoran , Yin Wen , Cui Xilong , Jiao Wei
Published: June 2024

Background

Endoscopic spine lumbar interbody fusion (Endo-LIF) is well-regarded within the academic community. However, it presents challenges such as intraoperative disorientation, high rates of nerve damage, a steep learning curve, and prolonged surgical times, often occurring during the creation of the operative channel. Furthermore, the undefined safe operational zones under endoscopy continue to pose risks to surgical safety. We aimed to analyse the anatomical data of Kambin’s triangle via CT imaging to define the parameters of the safe operating area for transforaminal posterior lumbar interbody fusion (TPLIF), providing crucial insights for clinical practice.

Methods

We selected the L4–L5 intervertebral space. Using three-dimensional (3D), we identified Kambin’s triangle and the endocircle within it, and recorded the position of point ‘J’ on the adjacent facet joint as the centre ‘O’ of the circle shifts by angle ‘β.’ The diameter of the inscribed circle ‘d,’ the abduction angle ‘β,’ and the distances ‘L1’ and ‘L2’ were measured from the trephine’s edge to the exiting and traversing nerve roots, respectively.

Results

Using a trephine with a diameter of 8 mm in TPLIF has a significant safety distance. The safe operating area under the TPLIF microscope was also clarified.

Conclusions

Through CT imaging research, combined with 3D simulation, we identified the anatomical data of the L4–L5 segment Kambin’s triangle, to clarify the safe operation area under TPLIF. We propose a simple and easy positioning method and provide a novel surgical technique to establish working channels faster and reduce nerve damage rates. At the same time, according to this method, the Kambin’s triangle anatomical data of the patient’s lumbar spine diseased segments can be measured through CT 3D reconstruction of the lumbar spine, and individualised preoperative design can be conducted to select the appropriate specifications of visible trephine and supporting tools. This may effectively reduce the learning curve, shorten the time operation time, and improve surgical safety.
Comparative effectiveness of alternative spontaneous breathing trial techniques: a systematic review and network meta-analysis of randomized trials
Authors: Burns Karen E. A. , Sadeghirad Behnam , Ghadimi Maryam , Khan Jeena , Phoophiboon Vorakamol , Trivedi Vatsal , Gomez Builes Carolina , Giammarioli Benedetta , Lewis Kimberley , Chaudhuri Dipayan , Desai Kairavi , Friedrich Jan O.
Published: June 2024

Background

The spontaneous breathing trial (SBT) technique that best balance successful extubation with the risk for reintubation is unknown. We sought to determine the comparative efficacy and safety of alternative SBT techniques.

Methods

We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2023 for randomized or quasi-randomized trials comparing SBT techniques in critically ill adults and children and reported initial SBT success, successful extubation, reintubation (primary outcomes) and mortality (ICU, hospital, most protracted; secondary outcome) rates. Two reviewers screened, reviewed full-texts, and abstracted data. We performed frequentist random-effects network meta-analysis.

Results

We included 40 RCTs (6716 patients). Pressure Support (PS) versus T-piece SBTs was the most common comparison. Initial successful SBT rates were increased with PS [risk ratio (RR) 1.08, 95% confidence interval (CI) (1.05–1.11)], PS/automatic tube compensation (ATC) [1.12 (1.01 –1.25), high flow nasal cannulae (HFNC) [1.07 (1.00–1.13) (all moderate certainty), and ATC [RR 1.11, (1.03–1.20); low certainty] SBTs compared to T-piece SBTs. Similarly, initial successful SBT rates were increased with PS, ATC, and PS/ATC SBTs compared to continuous positive airway pressure (CPAP) SBTs. Successful extubation rates were increased with PS [RR 1.06, (1.03–1.09); high certainty], ATC [RR 1.13, (1.05–1.21); moderate certainty], and HFNC [RR 1.06, (1.02–1.11); high certainty] SBTs, compared to T-piece SBTs. There was little to no difference in reintubation rates with PS (vs. T-piece) SBTs [RR 1.05, (0.91–1.21); low certainty], but increased reintubation rates with PS [RR 2.84, (1.61–5.03); moderate certainty] and ATC [RR 2.95 (1.57–5.56); moderate certainty] SBTs compared to HFNC SBTs.

Conclusions

SBTs conducted with pressure augmentation (PS, ATC, PS/ATC) versus without (T-piece, CPAP) increased initial successful SBT and successful extubation rates. Although SBTs conducted with PS or ATC versus HFNC increased reintubation rates, this was not the case for PS versus T-piece SBTs.
A randomised controlled trial of the Learning Skills Together (LST) intervention to improve dementia family caregivers’ self-efficacy with complex care
Authors: Meyer Kylie , Lee Kyungmi , Thorngthip Sutthinee , Burant Patricia , Lippe Megan , Neidre Daria , White Carole , Norman Rocio , Choi Byeong Yeob , Glover Crystal M. , Bell Janice , Hepburn Kenneth
Published: June 2024

Background

Nearly two-thirds of family caregivers of persons living with Alzheimer’s disease or related dementias (AD/ADRD) provide complex care, including medical care. Family caregivers typically receive little to no training on how to provide this care. Furthermore, family caregivers simultaneously grapple with the presence of behavioral and psychological symptoms of dementia (BPSD), diminished communication abilities, and comorbidities such as diabetes. We developed Learning Skills Together (LST), a 6-week digitally delivered psychoeducational program, to facilitate family caregiver abilities to administer complex care tasks. The goal of the present study is to test the efficacy of LST and to reduce adverse outcomes associated with caregiving, such as depressive symptomology and negative appraisal of BPSD.

Methods

To test the efficacy of LST, we will conduct a two-arm single-site randomized controlled trial (RCT) with N = 200 family caregivers of persons living with AD/ADRD. Eligible family caregivers will be randomly assigned to participate in either the LST intervention or a structurally equivalent control condition focused on healthy living. All family caregivers will complete four surveys, including a baseline survey administered prior to randomization, a post-intervention survey, and a 3- and 6-month follow-up survey to assess change in study outcomes. Between-group comparisons of each outcome will be evaluated using generalized estimating equation models. Mediation analyses will assess family caregiver self-efficacy as the intervention’s mechanism of change in depressive symptomology and BPSD. We will also examine caregiver race, ethnicity, and gender as effect modifiers of the intervention.

Discussion

LST findings will inform the field of AD/ADRD and caregiving regarding optimally supporting family caregivers in managing complex care tasks. If efficacious, the LST intervention will support family caregivers in preserving their own mental health while providing complex care.

Trial registration

Clinical Trials.gov NCT05846984. This study was registered on May 6, 2023.
Carbon-wise utilization of lignin-related compounds by synergistically employing anaerobic and aerobic bacteria
Authors: Meriläinen Ella , Efimova Elena , Santala Ville , Santala Suvi
Published: June 2024

Background

Lignin is a highly abundant but strongly underutilized natural resource that could serve as a sustainable feedstock for producing chemicals by microbial cell factories. Because of the heterogeneous nature of the lignin feedstocks, the biological upgrading of lignin relying on the metabolic routes of aerobic bacteria is currently considered as the most promising approach. However, the limited substrate range and the inefficient catabolism of the production hosts hinder the upgrading of lignin-related aromatics. Particularly, the aerobic O-demethylation of the methoxyl groups in aromatic substrates is energy-limited, inhibits growth, and results in carbon loss in the form of CO2.

Results

In this study, we present a novel approach for carbon-wise utilization of lignin-related aromatics by the integration of anaerobic and aerobic metabolisms. In practice, we employed an acetogenic bacterium Acetobacterium woodii for anaerobic O-demethylation of aromatic compounds, which distinctively differs from the aerobic O-demethylation; in the process, the carbon from the methoxyl groups is fixed together with CO2 to form acetate, while the aromatic ring remains unchanged. These accessible end-metabolites were then utilized by an aerobic bacterium Acinetobacter baylyi ADP1. By utilizing this cocultivation approach, we demonstrated an upgrading of guaiacol, an abundant but inaccessible substrate to most microbes, into a plastic precursor muconate, with a nearly equimolar yields (0.9 mol/mol in a small-scale cultivation and 1.0 mol/mol in a one-pot bioreactor cultivation). The process required only a minor genetic engineering, namely a single gene knock-out. Noticeably, by employing a metabolic integration of the two bacteria, it was possible to produce biomass and muconate by utilizing only CO2 and guaiacol as carbon sources.

Conclusions

By the novel approach, we were able to overcome the issues related to aerobic O-demethylation of methoxylated aromatic substrates and demonstrated carbon-wise conversion of lignin-related aromatics to products with yields unattainable by aerobic processes. This study highlights the power of synergistic integration of distinctive metabolic features of bacteria, thus unlocking new opportunities for harnessing microbial cocultures in upgrading challenging feedstocks.
Effect of zinc supplementation on glycemic biomarkers: an umbrella of interventional meta-analyses
Authors: Daneshvar Maziar , Ghaheri Mohammad , Safarzadeh Diba , Karimi Fatemeh , Adib-Hajbagheri Parisa , Ahmadzade Mohadese , Haedi Amir
Published: June 2024

Background

Several studies have evaluated the effects of zinc supplementation on glycemic biomarkers in humans and have demonstrated varying results. We systematically evaluated the literature and performed an umbrella meta-analysis of the effects of zinc supplementation on type 2 diabetes biomarkers.

Methods

A comprehensive literature search was conducted in the following databases; PubMed, Embase, Embase, Cochrane Library, Scopus, and Web of Science for studies published up to March 10, 2024.

Results

Zinc supplementation was effective in reducing serum FBS (WMD: − 13.58, 95% CI: − 17.38, − 9.77; p < 0.001; SMD: − 0.52, 95% CI − 0.79, − 0.25; p =  < 0.001), insulin (SMD: − 0.67, 95% CI − 0.96, − 0.38; p < 0.001), HOMA-IR levels (WMD − 0.52, 95% CI − 0.66, − 0.38; p < 0.001; SMD: − 0.78, 95% CI − 1.02, − 0.42; p < 0.001), and HbA1c (WMD: − 0.35, 95% CI − 0.43, − 0.27; p < 0.001).

Conclusion

Zinc supplementation significantly reduced FBS, HOMA-IR, insulin and HbA1c. These findings suggest that zinc is potentially an effective complementary intervention to improve type 2 diabetes biomarkers.
Identification of nutrition factors in the metabolic syndrome and its progression over time in older adults: analysis of the TUDA cohort
Authors: Lyons Oonagh C. , Kerr Maeve A. , Flynn Mary A. T. , Hoey Leane , Hughes Catherine F. , Caffrey Aoife , Laird Eamon , Moore Katie , Porter Kirsty M. , Cunningham Conal , McCarroll Kevin , Molloy Anne M. , Tracey Fergal , O’Kane Maurice , Strain J. J. , Ward Mary , McNulty Helene
Published: June 2024

Background

Nutrition is recognized as playing an important role in the metabolic syndrome (MetS), but the dietary components involved are unclear. We aimed to investigate nutrition factors in relation to MetS and its progression in older adults over a follow-up period of 5.4 years.

Methods

Community-dwelling adults (≥ 60y) from the Trinity-Ulster-Department-of-Agriculture study, sampled at baseline (2008–12) and follow-up (2014–18; n 953), were classified as ‘with MetS’ by having three or more of: waist circumference (≥ 102 cm, males; ≥ 88 cm, females); HDL-cholesterol (< 1.0 mmol/L, males; < 1.3 mmol/L, females); triglycerides (≥ 1.7 mmol/L); blood pressure (systolic ≥ 130 and/or diastolic ≥ 85 mmHg); and hemoglobin A1c (≥ 39 mmol/mol).

Results

MetS was identified in 67% of participants, increasing to 74% at follow-up. Predictors at baseline for the development of metabolic syndrome (MetS) at follow-up were higher waist circumference (odds ratio [95%CI]; 1.06 [1.01–1.11]), but not BMI, and increased triglyceride concentrations (2.01 [1.29–3.16]). In dietary analysis (at follow-up), higher protein (g/kg bodyweight/day) and monounsaturated fatty acid (g/day) intakes were each associated with lower risk of MetS (0.06 [0.02–0.20] and 0.88 [0.78–1.00], respectively), whilst higher protein was also associated with lower abdominal obesity (0.10 [0.02–0.51]) and hypertension (0.22 [0.00–0.80]). Furthermore, participants with, compared to without, MetS consumed less high-quality protein foods (P = 0.006) and more low-quality protein foods (P < 0.001), as defined by the protein digestibility-corrected amino acid score.

Conclusions

Dietary interventions targeting protein quantity and quality may have specific benefits in preventing or delaying the progression of MetS in at-risk older people, but this requires investigation in the form of randomized trials.
A multi-method exploration of a cardiac rehabilitation service delivered by registered Clinical Exercise Physiologists in the UK: key learnings for current and new services
Authors: Crozier Anthony , Graves Lee E. , George Keith P. , Richardson David , Naylor Louise , Green Daniel J. , Rosenberg Michael , Jones Helen
Published: June 2024

Background

Cardiac rehabilitation has been identified as having the most homogenous clinical exercise service structure in the United Kingdom (UK), but inconsistencies are evident in staff roles and qualifications within and across services. The recognition of Clinical Exercise Physiologists (CEPs) as a registered health professional in 2021 in the UK, provides a potential solution to standardise the cardiac rehabilitation workforce. This case study examined, in a purposefully selected cardiac exercise service that employed registered CEPs, (i) how staff knowledge, skills and competencies contribute to the provision of the service, (ii) how these components assist in creating effective service teams, and (iii) the existing challenges from staff and patient perspectives.

Methods

A multi-method qualitative approach (inc., semi-structured interviews, observations, field notes and researcher reflections) was employed with the researcher immersed for 12-weeks within the service. The Consolidated Framework for Implementation Research was used as an overarching guide for data collection. Data derived from registered CEPs (n = 5), clinical nurse specialists (n = 2), dietitians (n = 1), service managers/leads (n = 2) and patients (n = 7) were thematically analysed.

Results

Registered CEPs delivered innovative exercise prescription based on their training, continued professional development (CPD), academic qualifications and involvement in research studies as part of the service. Exposure to a wide multidisciplinary team (MDT) allowed skill and competency transfer in areas such as clinical assessments. Developing an effective behaviour change strategy was challenging with delivery of lifestyle information more effective during less formal conversations compared to timetabled education sessions.

Conclusions

Registered CEPs have the specialist knowledge and skills to undertake and implement the latest evidence-based exercise prescription in a cardiac rehabilitation setting. An MDT service structure enables a more effective team upskilling through shared peer experiences, observations and collaborative working between healthcare professionals.
Multiple evanescent white dot syndrome associated with COVID-19 infection: a case report
Authors: Ting Michael , Hsueh Jessica , Noori Jila
Published: June 2024

Background

To report a case of Multiple Evanescent White Dot Syndrome (MEWDS) one month after a COVID-19 infection in a female patient at an age unusual for the occurrence of this disease.

Case presentation

A 69-year-old Caucasian female reported the presence of floaters, photopsia, and enlarging vision loss in her left eye following the COVID-19 infection. Clinical and multimodal imaging was consistent with the MEWDS diagnosis. Fluorescein angiography examination revealed characteristic hyperfluorescent spots around the fovea in a wreath-like pattern. An extensive lab workup to rule out other autoimmune and infectious etiologies was inconclusive. Visual acuity and white dots resolved after a course of corticosteroids, which was confirmed on follow-up dilated fundus exam and multimodal imaging.

Conclusions

MEWDS is a rare white dot syndrome that may occur following COVID-19 infection in addition to other reported ophthalmic disorders following this infection.
Does hospital competition improve the quality of outpatient care? - empirical evidence from a quasi-experiment in a Chinese city
Authors: Peng Zixuan , Laporte Audrey , Wei Xiaolin , Sha Xinping , Coyte Peter C.
Published: June 2024

Background

Although countries worldwide have launched a series of pro-competition reforms, the literature on the impacts of hospital competition has produced a complex and contradictory picture. This study examined whether hospital competition contributed to an increase in the quality of outpatient care.

Methods

The dataset comprises encounter data on 406,664 outpatients with influenza between 2015 and 2019 in China. Competition was measured using the Herfindahl-Hirschman index (HHI). Whether patients had 14-day follow-up encounter for influenza at any healthcare facility, outpatient facility, and hospital outpatient department were the three quality outcomes assessed. Binary regression models with crossed random intercepts were constructed to estimate the impacts of the HHI on the quality of outpatient care. The intensity of nighttime lights was employed as an instrumental variable to address the endogenous relationship between the HHI and the quality of outpatient care.

Results

We demonstrated that an increase in the degree of hospital competition was associated with improved quality of outpatient care. For each 1% increase in the degree of hospital competition, an individual’s risk of having a 14-day follow-up encounter for influenza at any healthcare facility, outpatient facility, and hospital outpatient department fell by 34.9%, 18.3%, and 20.8%, respectively. The impacts of hospital competition on improving the quality of outpatient care were more substantial among females, individuals who used the Urban and Rural Residents Basic Medical Insurance to pay for their medical costs, individuals who visited accredited hospitals, and adults aged 25 to 64 years when compared with their counterparts.

Conclusion

This study demonstrated that hospital competition contributed to better quality of outpatient care under a regime with a regulated ceiling price. Competition is suggested to be promoted in the outpatient care market where hospitals have control over quality and government sets a limit on the prices that hospitals may charge.
Impact of extended lung protection during mechanical ventilation on lung recovery in patients with COVID-19 ARDS: a phase II randomized controlled trial
Authors: Costa Eduardo L. V. , Alcala Glasiele C. , Tucci Mauro R. , Goligher Ewan , Morais Caio C. , Dianti Jose , Nakamura Miyuki A. P. , Oliveira Larissa B. , Pereira Sérgio M. , Toufen Carlos , Barbas Carmen S. V. , Carvalho Carlos R. R. , Amato Marcelo B. P.
Published: June 2024

Background

Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery.

Methods

We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates.

Results

The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups.

Conclusions

The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial.

Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.
A multi path routing protocol with efficient energy consumption in IoT applications real time traffic
Authors: Abujassar Radwan S.
Published: June 2024

The extensive utilization of IoT applications leads to the aggregation of a substantial volume of data, presenting a crucial challenge in terms of data routing within these networks. RPL intentionally surpasses the limitations sometimes observed in low-power and lossy networks, which are particularly prevalent in IoT networks. The RPL protocol is designed specifically for static networks that do not involve mobility or topological changes. The RPL protocol guarantees continuous connectivity between nodes and mitigates the risk of data loss in stationary IoT applications that do not involve mobility or alterations in network configuration. The article utilizes a mobility aid technology known as network performance stability using the intelligent routing protocol (nPSIR), which expands upon RPL. The Mobility Support Entity (nPSIR) facilitates the displacement of all nodes, with the exception of the root node, and ensures uninterrupted connection during mobility. Moreover, it deals with the situation where there is a physical barrier between two interconnected nodes in a changing environment. In order to achieve this objective, it employs a dynamic trickle timer that operates within two distinct ranges. Furthermore, it utilizes a neighbor link quality table, a mechanism for selecting the most beneficial parent node in the event of migration, a measure of confidence, the identification of crucial regions, and a blacklist. Multiple simulations validate that nPSIR effectively decreases hand-off delay and improves packet delivery, despite the minor drawbacks of increased signaling costs and power consumption. The delivery ratio decreases the quantity of lost data packets and surpasses both RPL as a responsive protocol and mRPL as a proactive protocol in relation to mobility.
The brain–bone axis: unraveling the complex interplay between the central nervous system and skeletal metabolism
Authors: Shi Haojun , Chen Min
Published: June 2024

The brain–bone axis has emerged as a captivating field of research, unveiling the intricate bidirectional communication between the central nervous system (CNS) and skeletal metabolism. This comprehensive review delves into the current state of knowledge surrounding the brain–bone axis, exploring the complex mechanisms, key players, and potential clinical implications of this fascinating area of study. The review discusses the neural regulation of bone metabolism, highlighting the roles of the sympathetic nervous system, hypothalamic neuropeptides, and neurotransmitters in modulating bone remodeling. In addition, it examines the influence of bone-derived factors, such as osteocalcin and fibroblast growth factor 23, on brain function and behavior. The therapeutic potential of targeting the brain–bone axis in the context of skeletal and neurological disorders is also explored. By unraveling the complex interplay between the CNS and skeletal metabolism, this review aims to provide a comprehensive resource for researchers, clinicians, and students interested in the brain–bone axis and its implications for human health and disease.
No causal association between insomnia and bladder cancer: a bidirectional two-sample Mendelian randomization study
Authors: Du Lihuan , Wang Bohan , Wen Jiaming , Zhang Nan
Published: June 2024

Background

Previous observational studies have indicated a potential link between insomnia and bladder cancer, yet the underlying causal relationship remains uncertain. The current study employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate this association.

Methods

A two-sample MR analysis was conducted utilizing publicly available summary data from genome-wide association studies (GWAS) on insomnia and bladder cancer. Various regression methods including the inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode methods were employed for the MR analysis. The presence of pleiotropy and heterogeneity in the MR results was also assessed. Furthermore, additional sensitivity tests were performed to mitigate potential biases.

Results

No significant causal relationship was detected between insomnia and bladder cancer using IVW method (OR = 0.761, 95% CI 0.996–1.005; P = 0.76). Similarly, the IVW model did not reveal any causal effect of bladder cancer on the risk of insomnia (OR = 1.47, 95% CI 0.772–2.799; P = 0.24). Consistent results were obtained from the other four methods employed. There was no evidence of horizontal pleiotropy or heterogeneity in our MR analysis (P > 0.05). The sensitivity analyses further supported the reliability of the estimated causal effects.

Conclusions

This study presents no evidence for a causal relationship between insomnia and bladder cancer.
Origami manipulation by robot hand utilizing electroadhesion
Authors: Kitamori Hiroto , Dong Chenyu , Takizawa Masaru , Watanabe Shuya , Shintake Jun , Kimura Kohei , Kudoh Shunsuke
Published: June 2024

This study presents strategies for the three fundamental origami operations of grasping, bending, and folding using a novel robot hand and simple motions. These operations are executed using a simple geometric model and without any visual feedback or physical modeling not to restrict the motions. With a few applications in the field of paper manipulation, the electroadhesion technology is employed to perform single hand grasping. Bending is realized by a single hand utilizing the elasticity of origami and friction. Folding is performed by holding an origami with more than two points to fix it at any moment for preciseness. In addition to the design of hardware and motions, operations are demonstrated with general criteria for the crease precision evaluation.
Impact of an Ultra-Endurance Marathon on Cardiac Function in Association with Cardiovascular Biomarkers
Authors: Burger Achim Leo , Wegberger Claudia , Tscharre Maximilian , Kaufmann Christoph C. , Muthspiel Marie , Pogran Edita , Freynhofer Matthias K. , Szalay Alexander , Huber Kurt , Jäger Bernhard
Published: June 2024

Background

Participation in ultra-endurance races may lead to a transient decline in cardiac function and increased cardiovascular biomarkers. This study aims to assess alterations in biventricular function immediately and five days after the competition in relation to elevation of high-sensitivity cardiac Troponin I (hs-cTnI) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP).

Methods and Results

Fifteen participants of an ultramarathon (UM) with a running distance of 130 km were included. Transthoracic echocardiography and quantification of biomarkers was performed before, immediately after and five days after the race. A significant reduction in right ventricular fractional area change (FAC) was observed after the race (48.0 ± 4.6% vs. 46.7 ± 3.8%, p = 0.011) that persisted five days later (48.0 ± 4.6% vs. 46.3 ± 3.9%, p = 0.027). No difference in left ventricular ejection fraction (LVEF) was found (p = 0.510). Upon stratification according to biomarkers, participants with NT-proBNP above the median had a significantly reduced LVEF directly (60.8 ± 3.6% vs. 56.9 ± 4.8%, p = 0.030) and five days after the race (60.8 ± 3.6% vs. 55.3 ± 4.5%, p = 0.007) compared to baseline values. FAC was significantly reduced five days after the race (48.4 ± 5.1 vs. 44.3 ± 3.9, p = 0.044). Athletes with hs-cTnI above the median had a significantly reduced FAC directly after the race (48.1 ± 4.6 vs. 46.5 ± 4.4, p = 0.038), while no difference in LVEF was observed. No alteration in cardiac function was observed if hs-cTnI or NT-proBNP was below the median.

Conclusion

A slight decline in cardiac function after prolonged strenuous exercise was observed in athletes with an elevation of hs-cTnI and NT-proBNP above the median but not below.
Estimation of default and pricing for invoice trading (P2B) on crowdlending platforms
Authors: Corrales Cristian Marques , González Luis Alberto Otero , Santomil Pablo Durán
Published: June 2024

This study developed several machine learning models to predict defaults in the invoice-trading peer-to-business (P2B) market. Using techniques such as logistic regression, conditional inference trees, random forests, support vector machines, and neural networks, the prediction of the default rate was evaluated. The results showed that these techniques can effectively improve the detection of defaults by up to 56% while maintaining levels of specificity above 70%. Unlike other studies on the same topic, this was performed using sampling techniques to address the imbalance of classes and using different time periods for the training and test datasets to ensure intertemporal validation and realistic predictions. For the first-time, default explainability in the invoice-trading market was studied by examining the impact of macroeconomic factors and invoice characteristics. The findings highlighted that gross domestic product, exports, trade type, and trade bands are significant factors that explain defaults. Furthermore, the pricing mechanisms of P2B platforms were evaluated with the observed and implicit probabilities of the default to analyze the price risk adjustment. The results showed that price reflects a significantly higher implicit probability of default than observed default, which in turn suggests that underlying factors exist besides the borrowers’ probability of default.
Mitigating the escalating threat of infectious diseases outbreaks in tropical Africa: a perspective examination of challenges and strategies for future preparedness
Authors: Hassan Hakeem Kayode , Adigun Olaniyi Abideen , Manirambona Emery , Olaleke Noah Olabode , Abioye Micheal Sunday , Lucero-Prisno III Don Eliseo , Atewologun Faith Ayobami , Okesanya Olalekan John
Published: June 2024

Background

The escalating threat of infectious disease outbreaks in Africa, particularly emerging and re-emerging diseases, necessitates urgent and comprehensive action. The frequency of these outbreaks demands a robust enhancement of notification and reporting systems to enable swift public health interventions.

Main body of the abstract

Tropical diseases such as malaria, COVID-19, typhoid fever, yellow fever, arboviruses, cholera, rabies, schistosomiasis, tuberculosis, black fungus, meningitis, evolving pathogens, and antimicrobial resistance pose significant health risks globally, especially in Sub-Saharan Africa. The region faces complexities in healthcare, including weak systems, inadequate surveillance, socioeconomic disparities, and other issues. Poor health literacy, traditional practices, and distrust hinder effective disease control and contribute to disease emergence in Sub-Saharan Africa. Continuous research and global collaboration are essential to address these public health concerns, especially given Africa's unique challenges. Disease surveillance emerges as a highly effective strategy, crucial in regions vulnerable to infectious diseases. Establishing and strengthening comprehensive surveillance and reporting systems at individual, regional, national, and international levels is crucial due to the unpredictable nature of borderless outbreaks and their significant impact on morbidity, mortality, and economic stability. National surveillance relies heavily on effective control mechanisms within local community areas, necessitating the active involvement of medical personnel. Successful systems depend on functional countries using collected data for timely warnings and localized interventions. Stakeholders, including governments, health authorities, and international organizations, must collaborate urgently to implement and sustain these vital systems, mitigating the devastating consequences of infectious disease outbreaks. Additionally, a holistic approach is crucial, involving prioritized local production of vaccines, medicines, and diagnostics through initiatives like the African Vaccine Producers Initiative. This approach emphasizes the need for domestic pharmaceutical production, intensified public awareness campaigns, and the training of the next generation of global health leaders, ensuring multidimensional strategies, political and diplomatic skills, and evidence-based assessments.

Conclusion

Collaboration among governments, international organizations, and educational institutions is essential for successful policy advocacy and implementation to strengthen health security and mitigate the continuous rise of infectious diseases on the continent.
Network pharmacology, molecular docking study, and in vivo validation of the wound healing activity of the Red Sea soft coral Paralemnalia thyrsoides (Ehrenberg 1834) ethanolic extract and bioactive metabolites
Authors: el-dien Radwa Taher Mohie , Maher Sherif A. , Hisham Mohamed , Saber Entesar Ali , Khedr Amgad I. M. , Fouad Mostafa A. , Kamel Mohamed Salah , Mahmoud Basma Khalaf
Published: June 2024

Background

Wounds are a major health issue on a global scale, putting a great deal of financial, commercial, and social strain on healthcare organizations, patients, and individuals. So, this study aims to investigate the in vitro antioxidant activity of Paralemnalia thyrsoides soft coral total ethanolic extract. Also, bio-guided in vivo wound healing validation enhanced by the evaluation of related gene expression of Paralemnalia thyrsoides total extract, derived fractions, and three known metabolites was done. Furthermore, utilizing network pharmacology, we identified ten hub target genes associated with wound healing, including AKT1(RAC-alpha serine/threonine–protein kinase), IL6 (interleukin-6), MAPK3 (mitogen-activated protein kinase 3), MMP9 (matrix metalloproteinase 9), and APP (amyloid P protein precursor). We conducted molecular docking to assess how the three compounds interact with these hub genes and inflammatory cytokines (IL-1β (interleukin-1 beta), TGF-β (transforming growth factor-beta), TNF-α (tumor necrosis factor-alpha), and NF-KB (nuclear factor-kappa B) linked to wound healing.

Results

In vitro antioxidant activity of the total ethanolic extract of Paralemnalia thyrsoides revealed potent scavenging activity against H2O2 with IC50 of 178.62 μg/mL. Additionally, the bio-guided scheme of the in vivo wound healing assay leads to the most active fraction, petroleum ether, with a healing percentage of 85% ± 4. Several chromatographic procedures upon petroleum ether fraction led to the isolation of three known compounds with significant in vivo wound healing potential which are recognized as triacontan-1-ol (1), 24-methylcholesterol (2) 6α-acetyl-7α-acetate-1(10)-α-13-nornardosine [C16H24O4] (3). Noteworthy downregulation in Cox-2 (Cyclooxygenase-2), Cox-1 (Cyclooxygenase-1), IL-1β, TGF-β, TNF-α, NF-KB, and INF-ϒ (interferon-ϒ) relative genes expression and upregulation in TGF-β, and IL-10 (interleukin-10) relative genes expression proved that compounds (3), (2), and (1) were, respectively, significant. The in silico study suggests that both C16H24O4 and 24-methyl cholesterol have potential in wound healing, possibly involving the regulation of RAC-alpha serine/threonine-protein kinase (AKT1).

Conclusion

Our study highlights the antioxidant and wound-healing potential of Paralemnalia thyrsoides soft coral that can be attributed to its diverse chemical metabolites. The in vivo and in silico findings highlighted that P. thyrsoides can be an effective remedy for wound restoration with the need for extensive future detailed clinical studies to prove these results.
Prospective validation of ctHPVDNA for detection of minimal residual disease and prediction of recurrence in patients with HPV-associated head and neck cancer treated with surgery.
Authors: Hirayama Shun , Al-Inaya Yana , Aye Ling , Bryan Michael E. , Das Dipon , Mendel Julia , Naegele Saskia , Faquin William C , Sadow Peter , Fisch Adam S. , Lin Derrick , Varvares Mark A , Feng Allen , Emerick Kevin S. , Deschler Daniel G. , Lawrence Michael S. , Iafrate A. John , Chan Annie , Richmon Jeremy , Faden Daniel
Published: June 2024

6010

Background: Prediction of minimal residual disease (MRD) following surgery, and thus the need for adjuvant therapy, is currently based on clinicopathologic risk factors which have poor individual prognostic capacity. We previously reported that MRD detection by ctHPVDNA droplet digital (dd)PCR as early as post-operative day (POD) 1 is predictive of recurrence in stage I-II HPV+HNSCC patients. Here, we applied a significantly more sensitive custom whole genome hybrid-capture-based next generation sequencing assay, termed HPV-DeepSeek, to validate the prognostic capacity of ctHPVDNA detection and explore the optimal timing of MRD testing in HPV+HNSCC patients. We tested the primary hypothesis that patients with MRD detection within 6 weeks of surgery would have inferior PFS at 2 years and the secondary hypothesis that patients with ctHPVDNA positivity detected at any point following treatment completion would have inferior PFS at 2 years. Methods: 98 patients with HPV+HNSCC were prospectively enrolled with a mean follow-up of 712 days. All patients underwent surgery as primary treatment and clinicopathologic adjusted adjuvant treatment. 10ml blood samples were collected before surgery, in the post-operative period (POD 1-42), and serially in follow-up. MRD was defined as a lack of ctHPVDNA clearance during the 6 weeks following surgery. Cell free DNA was extracted from plasma and run on HPV-DeepSeek, and on existing ddPCR assays for head to head comparisons. Results: 96/98 (98%) of patients had detectable ctHPVDNA pre-treatment. 30/98 patients (31%) were MRD positive. Patients who were MRD positive had significantly worse 2 years PFS compared to MRD negative patients (78% vs 98%, P=0.0009). Predictive performance improved by limiting time points to POD 7-42 (2 year PFS 60% vs 97%, P<0.0001) as significantly fewer patients were MRD positive >1 week after surgery, suggesting the use of an ultra-sensitive assay such as HPV-DeepSeek requires adjustment of MRD time points. Patients with detectable ctHPVDNA following completion of all treatment had significantly worse 2-year PFS compared to patients without detectable ctHPVDNA (0% vs 97%, P<0.0001). 7/98 patients had cancer recurrence during follow-up that was detected by ctHPVDNA with a mean lead time of 207 days (35-518) to clinical diagnosis. Conclusions: ctHPVDNA detection by HPV-DeepSeek is a highly specific biomarker of MRD in HPV+HNSCC, accurately predicts disease progression and detects recurrence earlier than standard care clinical.
Development and validation of an assay to quantify plasma cell-free human papillomavirus DNA for 13 high-risk types that cause 98% of HPV-positive cancers.
Authors: Wotman Michael , Xiao Weihong , Du Robyn , Jiang Bo , Liu Suyu , Gillison Maura L.
Published: June 2024

6065

Background: Plasma cell-free HPV DNA (cfHPV) may be a valuable tool for identification of patients with local-regionally advanced HPV-positive cancers at risk for recurrence after chemoradiation. Technical validation is required for use as an integral biomarker in a prospective clinical trial. Methods: Cell-Free 13 (i.e., CF13) is a digital-droplet PCR assay for quantification of 13 high-risk HPV types and control ERV3 in plasma that considered both variant sequences into primer/probe design and a distance matrix in phylogenetic analysis in multiplex combinations. Oligonucleotides/plasmids encoding type-specific E6/E7 regions were used as positive controls. Limit of blank, detection, quantification (LoB, LoD, LoQ), linear range, inter- and intra-assay coefficients of variation (CoV), and type-specific cross-reactivity were determined as were sensitivity and specificity for an HPV-positive diagnosis in a cohort of 278 oropharyngeal/unknown primary/oral cavity cancers tested for HPV by E6/E7 mRNA qRT-PCR or p16 IHC and HPV in situ hybridization. Results: Under identical assay conditions, the LoB, LoD and linear range were <1, 5 and 5 to 200,000 virus copies without HPV type-specific cross-reactivity. Multiplexing had no effect on LoD or linearity. LoQ was 16 copies/ml plasma for all 13 HPV types. For 80 and 10,000 copies per ml, inter-assay CoV ranged from ~15-28% and ~3.2-4.6% and intra-assay CoV ranged from ~16-38% and 0.2-3.3%, respectively. cfDNA purification method (manual v automated; extraction efficiency 142% and 91% for 16 and 10,000 HPV16 copies/ml), input plasma volume (1, 2, or 4 ml), total background cfDNA (<1800ng) or genomic DNA (<700ng) did not affect quantification. For a diagnosis of HPV-positive cancer, sensitivity and specificity were 91.1% (214/235) and 97.7% (42/43), respectively. cfHPV was associated with gender, race, T stage, N stage, and primary treatment modality. When compared to below the median (≤230 copies/ml), cfHPV above the median was associated with worse progression-free survival (HR=2.26, 95% CI 1.23-4.17, p=0.009) in univariate analysis. However, this was no longer significant after adjustment for age, T stage, and M stage (HRadj=1.78, 95% CI 0.95-3.35, p=0.07). Conclusions: CF13 has high sensitivity, accuracy, precision, linearity, HPV type-specificity, and robustness, offering a rigorously validated assay applicable to ~98% of patients with HPV-positive cancer. CF13 had excellent clinical sensitivity and specificity for a diagnosis of HPV-positive OPC.
Survival outcomes of concurrent radiotherapy and toripalimab versus radiotherapy alone for elderly patients with postoperative head and neck squamous cell carcinoma unfit for cisplatin.
Authors: Dou Shengjin , Jiang Wen , Ye Lulu , Li Rongrong , Zhu Guopei
Published: June 2024

6099

Background: For elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the role of postoperative concurrent chemotherapy was controversial since the intolerable toxicities and increased acute mortality, thus, radiotherapy alone was recommended. We aimed to assess if addition of toripalimab (anti-PD-1) to radiotherapy could improve treatment outcomes for this patient population. Methods: This trial was an, open-label, phase 2, randomized study.We randomly assigned (1:1) patients aged>65 years, with ECOG Performance Status(PS) of 0–2, and with postoperative Stage III-IV (AJCC 8th Staging system) HNSCC unfit for cisplatin to concurrent radiotherapy (60-66Gy) and toripalimab (240mg on D0, D21 and D42)(RT+PD-1 group) or radiotherapy alone(RT group). The primary endpoint was 2-year disease free survival (DFS). It is hypothesized to detect a difference between arms of 45%-65% in 2-year DFS. Results: Between September 2020 and May 2023, 87 patients were randomly assigned (43 in RT+PD-1 group and 44 in RT group). The median age were 71.0 years (range 66-81) for the RT+PD-1 group and 72.5 years (range 67-80 years) for RT group. In the RT+PD-1 group, 35 (81.4%) patients received at least one dose of toripalimab; 38 (88.3%) patients in the RT+PD-1 group and 36 (81.8%) patients in the RT group complete the planed radiation dose. Median follow-up was 24 months in both arms. The 2-year DFS was 55.3% with RT+PD-1 and 51.2% with RT alone (p=0.866), and the 2-year OS was 63.3% with RT+PD-1 and 78.4% with RT alone(p=0.557). In RT+PD-1 group, 18(41.8%) patients were CPS≥20%; 2-year DFS was 72.2% in patients with CPS≥20%, which was 53.8% in patients with CPS<20 (p=0.412). Conclusions: The primary objective of prolonging DFS with concurrent radiotherapy and toripalimab in elderly patients unfit for cisplatin with locally advanced HNSCC was not met. For patients with CPS≥20, further study still warranted to evaluate the benefit of toripalimab in this patient setting. Biomarker analysis is still ongoing. Clinical trial information: NCT04523883 .