bluuebunny/crossref_metadata_2025 huggingface dataset:
DESIGN AND ANALYSIS OF FIXED OFFSHORE STRUCTURE â€“ AN OVERVIEW
Authors: Mukhlas Nurul â€˜Azizah , Shuhaimy Nurfatin Abdullah , Johari Muhammad Bukhari , Mat Soom Ezanizam , Abu Husain Mohd Khairi , Mohd Zaki Noor Irza
Published: July 2024

Construction of offshore structures is more complex than onshore structures in terms of structural response and its loading system. The high dependency on the environment with high level of uncertainties is the main factor that contributes to the complexity of design and construction process. Better understanding on the type of structures and load exposed to it are required to maintain the high integrity of the operation life. An overview of the design and analysis of offshore structure in the case of fixed platform will be discussed in this paper. It comprises of the fundamental principle of wave dynamic, the dominant load acting on the structure, method used to quantify the responses and probability of failure that should be considered at the design stage. It is mainly to provide understanding and guideline for the purpose of the design phase. Description in details can be obtained through further reading based on references that have been cited in the content.
SEISMIC SAFETY EVALUATION OF ABDUL MANNAN OVERPASS IN CHITTAGONG, BANGLADESH
Authors: Bhuiyan M. A. Rahman , Alim Hafizul
Published: July 2024

A number of multi-span overpasses in major cities of Bangladesh, such as Dhaka (the capital city) and Chittagong (the principal seaport city) have been constructed for the last few years with a view to reducing the traffic congestion at critical junctions. Abdul Mannan overpass is one of these, which is located in Chittagong city. It has been launched in the year of 2012 with a prime objective of reducing the traffic congestion within Chittagong city. This study is devoted towards assessing seismic safety of this overpass, which comprises in two phases: the first phase is dedicated towards the evaluation of seismic lateral strength and ductility whereas the second phase is aimed at assessing seismic fragility and retrofit of the overpass. In this regard, the first phase utilizes the ductility method as suggested by Japan Road Association (JRA) to evaluate lateral strength and ductility of piers of the overpass considering their different modes of failure. The lateral strengths of pier sections in bending are obtained based on their nonlinear sectional analyses results, while the shear strengths are estimated using JRA suggested method. The fiber models with conventional constitutive models for concrete and steel are used to obtain the moment-curvature relationships at critical sections of the overpass pier. The pushover analysis method is employed to derive the force-displacement relationships of piers using the results of the moment-curvature relationships. Subsequently, the lateral seismic demand, allowable lateral force, yield displacement, ultimate displacement and displacement ductility are obtained using the standard methods. In the second phase, the nonlinear dynamic analysis of a typical pier of the overpass is carried out for seismic fragility assessment followed by an assessment of seismic retrofit strategy suitable for the overpass. The numerical results of the study indicate that most of the piers of the overpass do not comply seismic safety requirements for design earthquake ground motion rerecords, which warrants the retrofit of piers of the overpass.
SEISMIC FRAGILITY ASSESSMENT AND RETROFIT OF A GOVERNMENT HOSPITAL BUILDING IN CHITTAGONG, BANGLADESH
Authors: AbulHasan Md. , Bhuiyan Md. Abdur Rahman
Published: July 2024

Chittagong Medical College Hospital (CMCH) is one of the most important government hospitals in Bangladesh. It is located in the heart of Chittagong city, the only port city of Bangladesh. Bangladesh National Building Code (BNBC) is the only official document, which has been used since 1993 as guidelines for seismic design of buildings. As per the guidelines of BNBC, the CMCH building was designed for an earthquake ground motion having a return period of 200 years. However, the revised version of BNBC has suggested that the building structures shall be designed for an earthquake ground motion having a return period of 2475 years. It is mentioned that a single seismic performance objective, the life safety, of the building is considered in both versions of BNBC. Considering the significant importance of CMCH building in providing the emergency facilities during and after the earthquake, it is indispensable to evaluate its seismic vulnerability for the two types of earthquake ground motion records having return period of 200 (Type-I) and 2475 (Type-II) years. In this regard, this paper deals with the seismic vulnerability assessment of the existing ancillary building (AB) of CMCH. The seismic vulnerability of building is usually expressed in the form of fragility curves, which display the conditional probability that the structural demand (structural response) caused by various levels of ground shaking exceeds the structural capacity defined by a damage state. The analytical method based on elastic response spectrum analyses results is used in evaluating the seismic fragility curves of the building. To the end, 3-D finite element model of the building subjected to 18 ground motion records having PGA of 0.325g to 0.785g has been used in theresponse spectrum analysis in order to evaluate its inter-story-drift ratio (IDR), an engineeringdemand parameter (EDP) for developing fragility curves. The analytical results have shown thatstructural deficiencies exist in the existing ancillary building (AB) for the Type-II earthquakeground motion record, which requires the building to be retrofitted to ensure that the existingancillary building (AB) becomes functional during and after the Type-II earthquake groundmotion record.
ASSESSMENT OF IMPACT OF LAND USE TYPES ON SOIL ORGANIC CARBON CONTENT IN SOUTH WEST, NIGERIA
Authors: Omofunmi Olorunwa Eric , Omotayo Best Ayoyimika
Published: July 2024

The present study attempts to relate the soil organic carbon content with four different land uses (Faculty of Agriculture Teaching and Research farm, cashew plantation and Agricultural and Bioresources experimental farm and oil palm plantation) which come under South west, Nigeria. The objective of the study was to assess the effects of different land uses on soil organic carbon. The sampled soils were collected from different land uses at 0â€“15 cm (surface), 15 â€“ 30 cm and 30 - 45 cm (sub-surface) depth and were analyzed for soil physical properties with standard procedures. Data were analysed using descriptive statistics and analysis of variance (ANOVA). The results indicated that the oil palm plantation land use recorded the highest mean of soil organic carbon content compared with other land use types at 0 â€“ 15 cm soil depth (23 Â±4 g kg-1), which was 1.5, 2.6 and 53.3 % more than in the Faculty of Agriculture Teaching and Research farm land, the cashew plantation land and the Agricultural and Bioresources experimental farm land. This is attributed to more inputs of litter fall and reduced decomposition of organic matter. Similarly, the lowest soil organic carbon content under Agricultural and Bioresorces engineering as compared to others was attributed to reduce of organic matter and frequent tillage which encouraged oxidation of organic matter. The finding indicated that the means of soil organic carbon were significantly different (P < 0.05) between the land use types. Conservation farming should be practiced
Residual Strain and Joint Pressurization Maintain Collagen Tension for On-Joint Lumbar Facet Capsular Ligaments
Authors: Gacek Elizabeth , Ellingson Arin M. , Barocas Victor H.
Published: July 2024

Modeling the lumbar facet capsular ligament's (FCL) mechanical behavior under various physiological motions has often been a challenge due to limited knowledge about the on-joint in situ ligament state arising from attachment to the bone or other internal loads. Building on prior work, this study presents an enhanced computational model of the lumbar facet capsular ligament by incorporating residual strain and joint pressurization strain, factors neglected in prior models. Further, the model can predict strain and stress distribution across the ligament under various spinal motions, highlighting the influence of the ligament's attachment to the bone, internal synovial fluid pressurization, and distribution of collagen fiber alignment on the overall mechanical response of the ligament. Joint space inflation was found to influence the total observed stress and strain fields, both at rest and during motion. A significant portion of the ligament was found to be in tension, even in the absence of external load. Additionally, the model's ability to account for residual strain offers a more realistic portrayal of the collagen fibers and elastin matrix's role in ligament mechanics. We conclude that (1) computational models of the lumbar facet capsular ligament should not assume that the ligament is unloaded when the joint is in its neutral position, and (2) the ligament is nearly always in tension, which may be important in terms of its long-term growth and remodeling.
Genome and life-history evolution link bird diversification to the end-Cretaceous mass extinction
Authors: Berv Jacob S. , Singhal Sonal , Field Daniel J. , Walker-Hale Nathanael , McHugh Sean W. , Shipley J. Ryan , Miller Eliot T. , Kimball Rebecca T. , Braun Edward L. , Dornburg Alex , Parins-Fukuchi C. Tomomi , Prum Richard O. , Winger Benjamin M. , Friedman Matt , Smith Stephen A.
Published: July 2024

Complex patterns of genome evolution associated with the end-Cretaceous [Cretaceous-Paleogene (K–Pg)] mass extinction limit our understanding of the early evolutionary history of modern birds. Here, we analyzed patterns of avian molecular evolution and identified distinct macroevolutionary regimes across exons, introns, untranslated regions, and mitochondrial genomes. Bird clades originating near the K–Pg boundary exhibited numerous shifts in the mode of molecular evolution, suggesting a burst of genomic heterogeneity at this point in Earth’s history. These inferred shifts in substitution patterns were closely related to evolutionary shifts in developmental mode, adult body mass, and patterns of metabolic scaling. Our results suggest that the end-Cretaceous mass extinction triggered integrated patterns of evolution across avian genomes, physiology, and life history near the dawn of the modern bird radiation.
Host species shapes genotype, antimicrobial resistance, and virulence profiles of enterotoxigenic
Escherichia coli
(ETEC) from livestock in the United States
Authors: Fu Yezhi , Nawrocki Erin M. , M’ikanatha Nkuchia M. , Dudley Edward G.
Published: July 2024

Enterotoxigenic
Escherichia coli
(ETEC) are significant pathogen in both cattle and pigs, causing diarrhea in these animals and leading to economic losses in the livestock industry. Understanding the dissimilarity in genotype, antimicrobial resistance (AMR), and virulence between bovine and swine ETEC is crucial for development of targeted preventive and therapeutic approaches for livestock. However, a comprehensive study on this area remains lacking. Here, we performed whole-genome sequencing-based analyses of bovine (
n
= 554) and swine (
n
= 623) ETEC collected in the United States over a 53-year period. We identified distinct ETEC genotypes (
fimH
type, O antigen, H antigen, sequence type) in cattle and pigs. Furthermore, specific AMR and virulence profiles were associated with bovine and swine ETEC. Compared to swine ETEC, bovine ETEC were less diverse in genotypes and had a significantly (
P
< 0.001) lower number of AMR genes per isolate but higher co-occurrence of Shiga toxin and enterotoxin genes. Our results provide an overview of the key genomic differences between bovine and swine ETEC in the United States, which might be attributed to host adaptation and antibiotic usage practice. Ongoing surveillance and research are essential to monitor the genetic diversity and AMR patterns of ETEC in different host species.

IMPORTANCE

Enterotoxigenic
Escherichia coli
(ETEC)-associated diarrhea represent one of the most economically important diseases in the livestock industry. By analyzing over a thousand livestock-derived ETEC samples in the United States, our study unveiled a clear distinction in ETEC’s genetic traits (i.e., genotypes, antimicrobial resistance [AMR], and virulence profiles) that might be tied to the different use of antibiotics in cattle and pigs, and the bacteria’s adaptation to their specific animal hosts. This understanding is crucial for tailoring preventive and therapeutic strategies. It also highlights the significance of ongoing surveillance and research into the evolution of bacterial pathogens like ETEC in livestock by using advanced techniques such as whole-genome sequencing.
Association of oral fungal profiles with health status and bacterial composition in elderly adults receiving community support and home care service
Authors: Asakawa Mikari , Kageyama Shinya , Said Heba Shehta , Ma Jiale , Suma Shino , Furuta Michiko , Takeshita Toru
Published: July 2024

Fungi compose a minority but a common component of normal oral microbiota and contribute to oral and systemic health by interacting with bacterial inhabitants. This study investigated the relationship of oral fungal profiles to health status and bacterial profiles of 159 elderly adults receiving community support and home care services. Fungal and bacterial densities and compositions were determined based on the fungal ribosomal internal transcribed spacer region and bacterial 16S rRNA gene amplicon analyses, respectively. The total fungal density of 87 individuals exceeded 5,000 copies, and their microbiota was characterized by significantly less dense bacterial populations and lower relative abundances of oral health-associated taxa, such as
Neisseria perflava
and
Porphyromonas pasteri
, compared with those with less than 5,000 copies of fungi. These individuals were significantly older, had fewer teeth, had lower physical function, and comprised more denture users and individuals with cognitive decline. Fungal compositions were classified into three profiles (
Candida albicans
-dominant, non-
albicans Candida
-dominant, and non-
Candida
-dominant), and individuals with a non-
albicans Candida
-dominant profile exhibited significantly lower physical and cognitive function than those with the
Candida albicans
-dominant profile. These results demonstrate that a high-density fungal population co-occurs with poor oral and systemic health status of the host and dysbiosis of the bacterial community, and particularly, the overgrowth of non-
albicans Candida
species may be implicated in worsening systemic conditions.

IMPORTANCE

The interaction between fungal and bacterial components involved in the virulence of oral microbiota has received attention. This study demonstrates that an increase in fungal components is associated with a dysbiotic bacterial community and poor health status in elderly adults. Among individuals with a high-density fungal population, particularly, those with a non-
albicans Candida
-dominant profile had lower physical and cognitive functions than those with a
C. albicans
-dominant profile. These findings indicate that the evaluation of fungal components, in addition to the bacterial components, is important to understand the involvement of oral microbiota in oral and systemic diseases in elderly adults.
Complete genome sequence of an Indian outbreak strain of chikungunya virus
Authors: Laha Eshna , Jena Deepak , Biswas Viplov K. , Singh Sharad , Raghav Sunil K. , Pattnaik Asit K. , Chattopadhyay Soma
Published: July 2024

Here, we report the complete genome sequence of an Indian strain of chikungunya virus isolated from an infected patient from Hyderabad, Andhra Pradesh, India, during a massive outbreak in 2005–2006. The genome length spans 11,811 nucleotides and has a poly(A) tail of 29 residues at the 3′ end.
Complete genome sequence of
Bacillus paramobilis
sp. strain IMGN7 from soil
Authors: Jung Hoseong , Choi Sejin , Kim Yeongjun , Han Jeong A. , Lee Ho-Seok , Kim Eun Yu
Published: July 2024

Here, we report the complete genome sequence of
Bacillus paramobilis
sp. strain IMGN7, which was isolated from soil in South Korea. Its complete genome size is 5.28 Mbp. This genome will provide various insights for further studies about their function as biocontrol agents, such as bioremediation and antibiosis.
High Precision Ultrasonic Testing Method for Density of Engineering Plastics
Authors: Li Chenggang , Wang Lun , Sun Lihong , Chu Zhaojie , Liu Wei , Tao Jiagui
Published: July 2024

The density of engineering plastics is a key parameter for ensuring their safety and reliability. In order to achieve rapid and high-precision on-site detection, a method based on the acoustic pressure reflection coefficient is proposed. First, finite element simulation analysis was conducted to obtain the acoustic field distribution during ultrasound propagation under water immersion conditions. The correlation between interface echo intensity and material density was determined. Optimal detection parameters were designed to reduce measurement errors caused by beam overlap and diffusion attenuation. A water immersion ultrasonic experimental system was constructed, and the measurement accuracy of the method was tested using chlorinated polyvinyl chloride pipes. The results show that, compared to the measurement results of the Archimedean drainage method, the maximum error of ultrasonic measurements does not exceed 1.7%, and the overall variance is less than 1.2%. The measurement accuracy of this method is compared with the regression results of different machine learning models. It is demonstrated that, compared to regression methods based on variable correlation, this method retains the advantages of high efficiency and low cost in ultrasonic density measurement, while achieving higher measurement accuracy. Additionally, it does not require a dataset for training support, making it promising and valuable for practical applications.
Integrated care for children and young people with special health and care needs: a systematic review
Authors: Ghotane Swapnil , Hirve Raeena , Forman Julia , Tan Daniel , Achercouk Zak , Wolfe Ingrid
Published: July 2024

Context

There is a dearth of high-quality evidence on integrated, coordinated and cost-effective care for children with special health and care needs (CSHCN).

Objective

To assess the effectiveness of integrated/coordinated care models for CSHCN.

Data sources

Embase, Ovid Medline(R), HMIC Health Management Information Consortium, Maternity & Infant Care Database (MIDIRS), PsycARTICLES, PsycINFO, Social Policy and Practice, Cochrane Central Register of Controlled Trials (CENTRAL), Global Health and PubMed.

Study selection

Inclusion criteria comprised (1) randomised trials, including cluster randomised trials; (2) an integrated/coordinated care intervention; (3) for children and young people under 25 with special healthcare needs including medical complexity; (4) assessing child-centred outcomes, health-related quality of life among parents and carers, and health or social care use, processes of care and satisfaction with care.

Data extraction

Data were extracted and assessed by two researchers, and descriptive data were synthesised according to outcome and intervention.

Results

14 randomised controlled studies were included. Seven out of the 14 studies had a dedicated key worker/care coordinator as a vital part of the integrated/coordinated care intervention; however, the certainty of evidence for all outcomes was either ‘low’ or ‘very low’.

Limitations

Included studies were mostly from high-income countries. Variable study outcomes and quality of evidence precluded meta-analysis.

Conclusions

Limited evidence favours integrated care for CSHCN using a dedicated key worker/care coordinator; however, heterogeneity in study outcomes and definitions of CSHCN limit the strength and utility of evidence obtained. Recommendations are made for improving integrated care practice, research and evaluation which are important for evidence-based health services for CSHCN.

PROSPERO registration number

CRD42020209320.
Preclinical study and parallel phase II trial evaluating antisense STAT3 oligonucleotide and checkpoint blockade for advanced pancreatic, non-small cell lung cancer and mismatch repair-deficient colorectal cancer
Authors: Tang Chad , Hartley Genevieve P , Couillault Coline , Yuan Ying , Lin Heather , Nicholas Courtney , Srinivasamani Anupallavi , Dai James , Dumbrava Ecaterina E Ileana , Fu Siqing , Karp Daniel D , Naing Aung , Piha-Paul Sarina A , Rodon Ahnert Jordi , Pant Shubham , Subbiah Vivek , Yap Timonthy A , Tsimberidou Apostolia M , Guerrero Paola , Dhebat Sarah , Proia Theresa , Curran Michael A , Hong David S
Published: July 2024

Objective

To evaluate signal transducer and activator of transcription 3 (STAT3) inhibition we conducted a co-clinical trial testing danvatirsen, a STAT3 antisense oligonucleotide (ASO) and checkpoint inhibition in conjunction with preclinical experiments.

Methods and analysis

Orthotopically implanted pancreatic cancer (pancreatic adenocarcinoma (PDAC)) was treated with STAT3 ASO with immune checkpoint inhibition. Tumour infiltrating immune cell populations were characterised via flow cytometry. In vitro experiments evaluated STAT3 inhibition in pancreatic stellate cells (PSCs) and myeloid-derived suppressor cells (MDSCs).

A phase II trial employing a Simon II stage design tested the clinical efficacy of danvatirsen and durvalumab in non-small cell lung cancer (NSCLC), PDAC and mismatch repair-deficient colorectal cancer (MRD CRC). The primary objective was 4-month disease control rate (DCR).

Results

In vivo studies identified improvement in survival of PDAC implanted mice treated with STAT3 ASO and checkpoint inhibition. Within tumour-infiltrating lymphocytes there was expansion of CD4 and PD-1+ CD8 populations with STAT3 ASO.

Thirty-seven patients (29 PDAC, 7 NSCLC and 1 MRD CRC) from a single institution started treatment on trial between April 2017 and March 2020. No objective responses were observed. Four of six (66.7%, 95% CI 22.3% to 95.7%) NSCLC and 4 of 23 (17.4%, 95% CI 5% to 38.8%) PDAC patients exhibited 4-month DCR. Follow-up in vitro studies revealed an anti-inflammatory and pro-tumour effect of STAT3 ASO mediated by PSCs and MDSCs distinct from ablation of STAT3.

Conclusion

Although durvalumab and danvatirsen met the primary endpoint, no objective responses were observed. A rationale for the lack of objective responses is danvatirsen-induced myeloid immune suppression.

Trial registration number

NCT02983578
.
Impact of collegial midwifery assistance during second stage of labour on women’s experience: a follow-up from the Swedish Oneplus randomised controlled trial
Authors: Häggsgård Cecilia , Edqvist Malin , Teleman Pia , Tern Helena , Rubertsson Christine
Published: July 2024

Objective

To compare experiences of the second stage of labour in women randomised to assistance by one or by two midwives to reduce severe perineal trauma (SPT).

Design

Analysis of a secondary outcome within the Swedish Oneplus multicentre randomised trial.

Setting

Five obstetric units in Sweden between December 2018 and March 2020.

Participants

Inclusion criteria in the Oneplus trial were women opting for their first vaginal birth from gestational week 37+0 with a singleton pregnancy and a live fetus in the vertex presentation. Further inclusion criteria were language proficiency in Swedish, English, Arabic or Farsi. Exclusion criteria were multiple pregnancies, intrauterine fetal demise and planned caesarean section. Of the 3059 women who had a spontaneous vaginal birth, 2831 women had consented to participate in the follow-up questionnaire.

Interventions

Women were randomly assigned (1:1) to assistance by two midwives (intervention group) or one midwife (standard care) when reaching the second stage of labour.

Outcome measures

Data were analysed by intention to treat. Comparisons between intervention and standard care regarding experiences of the second stage of labour were evaluated with items rated on Likert scales. The Student’s t-test was used to calculate mean differences with 95% CIs.

Results

In total 2221 (78.5%) women responded to the questionnaire. There were no statistically significant differences regarding women’s experiences of being in control, feelings of vulnerability or pain. Women randomised to be assisted by two midwives agreed to a lesser extent that they could handle the situation during the second stage (mean 3.18 vs 3.26, 95% CI 0.01 to 0.15). Conducted subgroup analyses revealed that this result originated from one of the study sites.

Conclusions

The intervention’s lack of impact on the experience of the second stage is of importance considering the reduction in SPT when being assisted by two midwives.

Trial registration number

NCT03770962.
Effectiveness and cost-effectiveness of radiofrequency denervation versus placebo for chronic and moderate to severe low back pain: study protocol for the RADICAL randomised controlled trial
Authors: Ashton Kate E , Price Cathy , Fleming Leah , Blom Ashley W , Culliford Lucy , Evans Rebecca Nicole , Foster Nadine E , Hollingworth William , Jameson Catherine , Jeynes Nouf , Moore Andrew J , Orpen Neil , Palmer Cecily , Reeves Barnaby C , Rogers Chris A , Wylde Vikki
Published: July 2024

Introduction

Low back pain (LBP) is the leading global cause of disability. Patients with moderate to severe LBP who respond positively to a diagnostic medial nerve branch block can be offered radiofrequency denervation (RFD). However, high-quality evidence on the effectiveness of RFD is lacking.

Methods and analysis

RADICAL (RADIofrequenCy denervAtion for Low back pain) is a double-blind, parallel-group, superiority randomised controlled trial. A total of 250 adults listed for RFD will be recruited from approximately 20 National Health Service (NHS) pain and spinal clinics. Recruitment processes will be optimised through qualitative research during a 12-month internal pilot phase. Participants will be randomised in theatre using a 1:1 allocation ratio to RFD or placebo. RFD technique will follow best practice guidelines developed for the trial. Placebo RFD will follow the same protocol, but the electrode tip temperature will not be raised. Participants who do not experience a clinically meaningful improvement in pain 3 months after randomisation will be offered the alternative intervention to the one provided at the outset without disclosing the original allocation. The primary clinical outcome will be pain severity, measured using a pain Numeric Rating Scale, at 3 months after randomisation. Secondary outcomes will be assessed up to 2 years after randomisation and include disability, health-related quality of life, psychological distress, time to pain recovery, satisfaction, adverse events, work outcomes and healthcare utilisation. The primary statistical analyses will be by intention to treat and will follow a prespecified analysis plan. The primary economic evaluation will take an NHS and social services perspective and estimate the discounted cost per quality-adjusted life-year and incremental net benefit of RFD over the 2-year follow-up period.

Ethics and dissemination

Ethics approval was obtained from the London—Fulham Research Ethics Committee (21/LO/0471). Results will be disseminated in open-access publications and plain language summaries.

Trial registration number

ISRCTN16473239.
Study protocol of the HessenKohorte2042: a prospective, longitudinal cohort study characterising quality of life in people with Parkinson’s disease and their caregivers using a bio-psycho-social approach
Authors: Kleinholdermann Urs , Thieken Franziska , Ruppert-Junck Marina Christine , van Munster Marlena , Pedrosa Anna Julia , Stümpel Johanne , Hammes Vincent , Timmermann Lars , Woopen Christiane , Schmitz-Luhn Björn , Storms Anna , Golla Heidrun , Nater Urs M , Skoluda Nadine , Pfefferle Petra Ina , Pedrosa David José
Published: July 2024

Introduction

Quality of life (QoL) is of paramount importance as an outcome to monitor and guide therapies for people with Parkinson’s disease (PwPD). In particular, due to the heterogeneous symptoms that PwPD may experience during their disease course, QoL can deteriorate not only in patients but also in their caregivers, with a variety of psychosocial consequences. However, there is a lack of longitudinal studies that explore how QoL evolves over time and what factors are significant. Furthermore, holistic approaches that consider bio-psycho-social determinants are rare. In the worst cases, these gaps can lead to suboptimal care and therefore unmet needs for patients and their caregivers, resulting in unnecessary symptom burden and increased healthcare costs for society.

Methods and analysis

This prospective, longitudinal study will follow 1000 PwPD along with their caregivers for 20 years, with up to 40 semi-annual assessments. Patient data and sample collection will include clinical assessments, self-reported outcome measures focusing on QoL, biospecimen collection and MRI. Caregiver burden will be systematically assessed through self-administered questionnaires. The use of digitised surveys will allow efficient data collection and convenient assessment at home. Our primary objective is to attain a holistic understanding of QoL in PwPD and establish a tool to measure it. The secondary objective is to explore the psycho-social and biological variables associated with QoL of patients and caregivers over the progression of the disease. This will provide key information for diagnostic and prognostic prediction, therapeutic patient stratification and adaptation of therapy in the future.

Ethics and dissemination

The study was approved by the local ethics committee of the University Hospital of Marburg (study number: 209/19). The results will be disseminated by means of publication in peer-reviewed journals, international conference contributions, annual patient meetings and a dedicated website.

Trial registration number

German Clinical Trials Register (DRKS00023598).
Primary healthcare in the aftermath of the COVID-19 pandemic: a qualitative interview study in Sweden
Authors: Fernemark Hanna , Hårdstedt Maria , Skagerström Janna , Seing Ida , Karlsson Elin , Nilsen Per , Schildmeijer Kristina Görel Ingegerd
Published: July 2024

Objective

To explore how primary healthcare workers in Sweden experienced and perceived the long-term impact of the pandemic on their work.

Design

This is a descriptive qualitative study with individual semistructured interviews conducted 2 years after the onset of COVID-19. Data were analysed using an inductive thematic approach.

Setting

Swedish primary healthcare units in rural and urban locations.

Participants

29 healthcare providers (6 registered nurses, 7 assistant nurses, 8 physicians and 8 managers) in Swedish primary healthcare.

Results

Data analysis yielded three overarching themes: (1) primary healthcare still affected by the pandemic; (2) primary healthcare changes made permanent; and (3) lessons learnt for handling future crises affecting primary healthcare. The participants experienced a high workload, even after the pandemic, and concluded that it would take years to catch up both mentally and workwise. Four lessons were learnt for future handling of crises that might affect primary healthcare: the importance of creating a cohesive primary healthcare management system to provide clarity regarding recommendations for how primary healthcare personnel should work, the need for management support at all levels, restricting and adapting the flow of information for primary healthcare and ascertaining the necessary resources if primary healthcare is to take on additional tasks.

Conclusion

Two years after the onset of the COVID-19 pandemic, primary healthcare workers in Sweden experienced that their work was still affected by the pandemic. Our findings highlight the importance of ensuring sufficient recovery time and providing opportunities for reflection on the experiences of primary healthcare personnel. This also includes preparedness for managing the heavy workload and strained energy levels of healthcare workers in the aftermath of a crisis.
Timely integration of specialist palliative home care (SPHC) for patients with congestive heart failure, chronic obstructive pulmonary disease and dementia: qualitative evaluation of the experiences of SPHC physicians in the KOPAL trial
Authors: Schade Franziska , Hüttenrauch Danica , Schwabe Sven , Mueller Christiane A , Pohontsch Nadine Janis , Stiel Stephanie , Scherer Martin , Marx Gabriella , Nauck Friedemann
Published: July 2024

Objective

Chronic non-malignant diseases (CNMDs) are under-represented in specialist palliative home care (SPHC). The timely integration of SPHC for patients suffering from these diseases can reduce hospitalisation and alleviate symptom burdens. An intervention of an SPHC nurse–patient consultation followed by an interprofessional telephone case conference with the general practitioner (GP) was tested in the KOPAL trial (‘Concept for strengthening interprofessional collaboration for patients with palliative care needs’). As part of the trial, the aim of this study was to gain in-depth insights into SPHC physicians’ perspective on care with and without the KOPAL intervention for patients with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia (D).

Design

Qualitative evaluation of the KOPAL intervention from the perspective of SPHC physicians as part of the KOPAL trial. Thematic-focused narrative interviews analysed with grounded theory.

Setting

We conducted the KOPAL study and its qualitative evaluation in Lower Saxony and the greater Hamburg area, Germany.

Participants

11 physicians from 14 SPHC teams who participated in the trial were interviewed.

Results

A grounded theory of the necessity of collaboration between GPs and SPHC teams for patients with CHF, COPD and dementia was developed. From the perspective of SPHC physicians, patients with CNMD are generally difficult to manage in GP care. The timing of SPHC initiation is patient-specific, underscoring the need for collaboration between SPHC physicians and GPs. However, the primary mandate for healthcare should remain with GPs. SPHC physicians actively seek collaboration with GPs (eg, through the KOPAL intervention), viewing themselves as advisors for GPs and aspiring to collaborate as equal partners.

Conclusion

Effective communication and the negotiation of future interprofessional collaboration are essential for SPHC teams.

Trial registration number

DRKS00017795.
Improving Miscarriage Prevention Research: a survey exploring the expectations of service users and stakeholders (IMPRESS) – a study protocol for a UK-based survey
Authors: Black Naomi , Quenby Siobhan , Odendaal Joshua
Published: July 2024

Introduction

Interventional clinical trials in recurrent miscarriage use varying expected effect sizes to inform their sample size calculations. Often these are not informed by what stakeholders consider a meaningful treatment effect. Adaptive trial designs may integrate stakeholder views on trial success and futility but the criteria to inform this is lacking. This study aims to understand relevant stakeholder views of what is considered a worthwhile treatment effect for miscarriage prevention interventions and what is acceptable stopping criteria in miscarriage clinical trials.

Methods and analysis

The study is designed as a cross-sectional online anonymous survey. The survey presents different scenarios to respondents relating to varying target differences and probability thresholds and explores success and futility criteria for clinical trials. The survey was developed with personal and public involvement (PPI) through focus groups and a PPI partner. Eligible participants will be those with a personal history of miscarriage, including partners, and healthcare professionals who manage patients who experience a miscarriage. Convenience, snowball and purposive sampling techniques will be employed to invite eligible participants to complete the survey. The survey will be accepting responses for an initial 2-week pilot to check validity, prior to being open for a further 12 weeks. Descriptive analyses and linear regression analyses will synthesise the survey results.

Ethics and dissemination

Ethical approval was obtained from the NHS Research Ethics Committee North West—Greater Manchester East (23/NW/0322) on 30 January 2024. Informed consent will be obtained prior to survey completion. No personal identifying information will be collected. The results will be published in a relevant scientific journal and communicated through our institutional website.
Application of speaking valves in adult patients with tracheostomy: a protocol for a systematic review and meta-analysis
Authors: Duan Dan , Cui Wenyao , Liu Wenjie , Xie Jingying
Published: July 2024

Introduction

Tracheostomy is a common emergency procedure for critically ill patients to secure their airway. The speaking valve is a one-way ventilation valve that is attached to the end of the tracheostomy tube to help the patient remodel subglottic pressure. However, the efficacy and safety of speaking valves in adult patients with tracheostomy remain controversial. The purpose of this protocol is to describe and evaluate the effectiveness, safety and impact on the quality of life of speaking valves in adult patients with tracheostomy.

Methods and analysis

We will search four English databases (PubMed, Embase, Cochrane Library and Web of Science), grey literature websites and reference lists of original studies to screen for studies that might meet the criteria. The two authors will independently screen the literature, extract data and assess the quality and risk of bias of the included studies. The primary outcomes will focus on the patients’ swallowing function, vocalisation and quality of life. We will use a fixed effects model or a random effects model based on heterogeneity testing or a descriptive analysis only. The quality of evidence on the effects of interventions will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation.

Ethics and dissemination

This study is based on the literature in the database and does not require the approval of the ethics committee. The results will be disseminated through a peer-reviewed journal and conferences.

PROSPERO registration number

CRD42024502906.
Incidents and patterns ofcommotio cordisamong athletes in the USA from 1982 to 2023
Authors: Shore Erin , Moseley Garrett A , DeLong Randi , Register-Mihalik Johna , Drezner Jonathan A , Dickey Grant James , Mao Haojie , Cantu Robert C , Kucera Kristen L
Published: July 2024

Introduction

Commotio cordisis a rare event that occurs following blunt, non-penetrating trauma to the chest, precipitating a ventricular arrhythmia.Commotio cordisrequires immediate medical attention through cardiopulmonary resuscitation and defibrillation, often resulting in death.Commotio cordisis most common condition among young male athletes. The purpose of this study was to describe the incidents and patterns ofcommotio cordisamong young athletes participating in organised sports in the USA from academic years 1982-1983 through 2022-2023.

Methods

This was a retrospective, descriptive epidemiology study using surveillance data from the National Center for Catastrophic Sport Injury Research. The study included allcommotio cordisincidents captured in the database. We calculated descriptive statistics (counts and proportions) overall and stratified by outcome and athlete sport.

Results

Over the study period, 64 incidents of commotio cordis were captured. The majority occurred among males (n=60) and were caused by contact with an object/apparatus (n=39) or contact with another player (n=20). The most common sports were baseball (n=20), lacrosse (n=17) and football (n=13). Over half of these incidents resulted in death (n=34), although survival fromcommotio cordisincreased over the study period. A higher proportion of fatal incidents occurred among football athletes and were caused by contact with another player.

Conclusions

Commotio cordisremains most common among young male athletes who participate in organised baseball, lacrosse and football. Although survival has improved over time, greater awareness and emergency preparedness forcommotio cordisin an organised sport are needed to facilitate prompt recognition and intervention.
POSTN+cancer-associated fibroblasts determine the efficacy of immunotherapy in hepatocellular carcinoma
Authors: Wang Hao , Liang Yuan , Liu Zheng , Zhang Rui , Chao Jiashuo , Wang Mingming , Liu Mu , Qiao Lei , Xuan Zhengfeng , Zhao Haitao , Lu Ling
Published: July 2024

Objective

Hepatocellular carcinoma (HCC) poses a significant clinical challenge because the long-term benefits of immune checkpoint blockade therapy are limited. A comprehensive understanding of the mechanisms underlying immunotherapy resistance in HCC is imperative for improving patient prognosis.

Design

In this study, to systematically investigate the characteristics of cancer-associated fibroblast (CAF) subsets and the dynamic communication among the tumor microenvironment (TME) components regulated by CAF subsets, we generated an HCC atlas by compiling single-cell RNA sequencing (scRNA-seq) datasets on 220 samples from six datasets. We combined spatial transcriptomics with scRNA-seq and multiplexed immunofluorescence to identify the specific CAF subsets in the TME that determine the efficacy of immunotherapy in HCC patients.

Results

Our findings highlight the pivotal role of POSTN+CAFs as potent immune response barriers at specific tumor locations, as they hinder effective T-cell infiltration and decrease the efficacy of immunotherapy. Additionally, we elucidated the interplay between POSTN+CAFs and SPP1+macrophages, whereby the former recruits the latter and triggers increased SPP1 expression via the IL-6/STAT3 signaling pathway. Moreover, we demonstrated a spatial correlation between POSTN+CAFs and SPP1+macrophages, revealing an immunosuppressive microenvironment that limits the immunotherapy response. Notably, we found that patients with elevated expression levels of both POSTN+CAFs and SPP1+macrophages achieved less therapeutic benefit in an immunotherapy cohort.

Conclusion

Our research elucidates light on the role of a particular subset of CAFs in immunotherapy resistance, emphasizing the potential benefits of targeting specific CAF subpopulations to improve clinical responses to immunotherapy.
NAD+metabolism enzyme NNMT in cancer-associated fibroblasts drives tumor progression and resistance to immunotherapy by modulating macrophages in urothelial bladder cancer
Authors: Yang Meihua , Wang Bo , Hou Weibin , Zeng Honghui , He Wang , Zhang Xin-Ke , Yan Dong , Yu Hao , Huang Long , Pei Lu , Li Kaiwen , Qin Haide , Lin Tianxin , Huang Jian
Published: July 2024

Background

This study comprehensively investigates the association between the expression of nicotinamide N-methyltransferase (NNMT) and clinical outcomes of urothelial bladder cancer (UBC), as well as the molecular mechanisms by which NNMT in cancer-associated fibroblast (CAF) modulates tumor progression and immunotherapy resistance in UBC.

Methods

Single-cell transcriptomic analyses, immunohistochemical and immunofluorescence assays were performed on bladder cancer samples to validate the relationship between NNMT expression and clinical outcomes. A series of experiments, including chromatin immunoprecipitation assay, liquid chromatography tandem mass spectrometry assay, and CRISPR‒Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) knockout, together within vivomodels, have been established to determine the molecular functions of NNMT in CAFs in UBC.

Results

We demonstrated that elevated expression of the nicotinamide adenine dinucleotide (NAD+) metabolism enzyme NNMT in CAFs (NNMT+CAFs) was significantly associated with non-response to programmed death-ligand 1 (PD-L1) blockade immunotherapy in patients with UBC and predicted the unfavorable prognosis of UBC in two independent large cohorts. Targeting NNMT using the inhibitor 5-Amino-1-methylquinolinium iodide significantly reduced tumor growth and enhanced the apoptotic effects of the anti-PD-L1 antibody in UBC mouse models. Mechanistically, NNMT+CAFs recruit tumor-associated macrophages via epigenetic reprogramming of serum amyloid A (SAA) to drive tumor cell proliferation and confer resistance to programmed death-1/PD-L1 blockade immunotherapy.

Conclusions

NNMT+CAFs were significantly associated with non-response to PD-L1 blockade immunotherapy in patients with UBC. Elevated NNMT, specifically in CAFs, upregulates SAA expression and enhances the recruitment and differentiation of macrophages in the tumor microenvironment, thereby directly or indirectly promoting tumor progression and conferring resistance to immunotherapies in bladder cancer.
Living happily alone in Plato’s cave? On loneliness, technology and the metaphysics of presence
Authors: Askheim Clemet , Engebretsen Eivind , Haldar Marit
Published: July 2024

In a lot of research on loneliness and technology, there is an underlying premise that actual, physical presence is more real than ‘virtual’ presence. This premise is rarely explicit, yet it implies a hierarchy of reality, where the ‘here and now’ is always on top. In this theoretical paper, we examine this latent hierarchy and the understandings of presence and mediation it implies. We point towards potential consequences of this understanding for research on the role of technology in reducing loneliness and social isolation. To do this, we draw on the philosophical analysis made by Martin Heidegger and Jacques Derrida of what they called ‘the metaphysics of presence’. This is the tendency to privilege presence as the only immediate and truthful access to reality, whereas all forms of mediations constitute mere approximations, derivations and second-rate realities with dubious truth value. First, we present their diagnosis, and then we show how it pertains to research on virtual presence and loneliness by analysing some examples from this research. Finally, we discuss some potential implications of the metaphysics of presence through a case story compiled from our empirical research. Our foundational assertion is that the question of whether anyone experiences loneliness is an empirical and not a metaphysical question. If we want to properly understand loneliness and the potential for alleviating it through the use of teletechnologies, we might get off on the wrong foot if we carry with us assumptions suggesting the existence of ascending levels of reality and presence.
Study of the effects of external imaginary electric field and chiral chemical potential on quark matter
Authors: Yang Ji-Chong , Zhang Xin , Chen Jian-Xing
Published: July 2024

The behavior of quark matter with both external electric field and chiral chemical potential is theoretically and experimentally interesting to consider. In this paper, the case of simultaneous presence of imaginary electric field and chiral chemical potential is investigated using the lattice QCD approach with $$N_f=1+1$$

N
f

=
1
+
1

dynamical staggered fermions. We find that overall both the imaginary electric field and the chiral chemical potential can exacerbate chiral symmetry breaking, which is consistent with theoretical predictions. However we also find a non-monotonic behavior of chiral condensation at specific electric field strengths and chiral chemical potentials. The behavior of Polyakov loop in the complex plane is not significantly affected by chiral chemical potential in the region of the parameters considered.